Dyspepsia: organic versus functional.

Dyspepsia is the medical term for difficult digestion. It consists of various symptoms in the upper abdomen, such as fullness, discomfort, early satiation, bloating, heartburn, belching, nausea, vomiting, or pain. The prevalence of dyspepsia in the western world is approximately 20% to 25%. Dyspepsia can be divided into 2 main categories: "organic" and "functional dyspepsia" (FD). Organic causes of dyspepsia are peptic ulcer, gastroesophageal reflux disease, gastric or esophageal cancer, pancreatic or biliary disorders, intolerance to food or drugs, and other infectious or systemic diseases. Pathophysiological mechanisms underlying FD are delayed gastric emptying, impaired gastric accommodation to a meal, hypersensitivity to gastric distension, altered duodenal sensitivity to lipids or acids, altered antroduodenojenunal motility and gastric electrical rhythm, unsuppressed postprandial phasic contractility in the proximal stomach, and autonomic nervous system-central nervous system dysregulation. Pathogenetic factors in FD are genetic predisposition, infection from Helicobacter pylori or other organisms, inflammation, and psychosocial factors. Diagnostic evaluation of dyspepsia includes upper gastrointestinal endoscopy, abdominal ultrasonography, gastric emptying testing (scintigraphy, breath test, ultrasonography, or magnetic resonance imaging), and gastric accommodation evaluation (magnetic resonance imaging, ultrasound, single-photon emission computed tomography, and barostat). Antroduodenal manometry can be used for the assessment of the myoelectrical activity of the stomach, whereas sensory function can be evaluated with the barostat, tensostat, and satiety test. Management of FD includes general measures, acid-suppressive drugs, eradication of H. pylori, prokinetic agents, fundus-relaxing drugs, antidepressants, and psychological interventions. This review presents an update on the diagnosis of patients presenting with dyspepsia, with an emphasis on the pathophysiological and pathogenetic mechanisms of FD and the differential diagnosis with organic causes of dyspepsia. The management of uninvestigated and FD, as well as the established and new pharmaceutical agents, is also discussed.

Antiglycan antibodies in Greek patients with inflammatory bowel disease.

BACKGROUND: Antiglycan antibodies have recently been reported to be associated with Crohn's disease (CD). These antibodies include anti-Saccharomyces cerevisiae mannan antibodies (ASCA), anti-laminariobioside carbohydrate antibodies (ALCA), anti-chitobioside carbohydrate antibodies (ACCA), and anti-mannobioside carbohydrate antibodies (AMCA). AIMS: The aim of this study was to evaluate their diagnostic accuracy in Greek patients with inflammatory bowel disease (IBD). METHODS: Serum was collected from 191 patients with IBD (85 with ulcerative colitis (UC) and 106 with CD), 29 cases with other causes of intestinal inflammation and 96 healthy controls. Antiglycan antibodies were measured using commercially available enzyme immunoassays. RESULTS: Higher levels of antiglycan antibodies were detected in patients with CD compared to patients with UC and controls. Although all types of antiglycan antibodies had a high specificity for diagnosing CD, their sensitivity was rather low, with best results obtained with ASCA and ALCA (41.5 and 52.8%, respectively). Increased levels of ASCA and ALCA were associated with stricturing and penetrating disease phenotype, and the need for surgery (p < 0.05). CONCLUSIONS: Antiglycan antibodies in Greek IBD patients are significantly associated with CD, and especially to phenotypes of complicated disease, with ASCA and ALCA exhibiting the highest sensitivity.

Safety and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anemia in patients with inflammatory bowel disease.

BACKGROUND: Intravenous iron has been suggested as a safe and effective treatment of anemia complicating inflammatory bowel disease (IBD). Low molecular weight (LMW) iron dextran has the ability to administer the patient's total iron requirement in a single infusion. AIMS: The aim of this study was to assess the safety and efficacy of the total dose of LMW iron dextran infusion for the treatment of iron deficiency in IBD. METHODS: Fifty IBD patients (27 female, 35 Crohn's disease, 15 ulcerative colitis) were included in the study. Mean +/- standard deviation (SD) hemoglobin and ferritin levels before the infusion were 9.88 +/- 1.42 g/dl and 13.9 +/- 10.9 ng/ml, respectively. A 25-mg test dose was followed by infusion of the total dose of LMW iron dextran based on the iron deficit. Several clinical and laboratory parameters were measured before and on week 4 after infusion. RESULTS: Four patients (8%) developed adverse reactions during the test infusion and did not receive the total-dose infusion. Only one patient developed an allergic reaction during the total-dose infusion. In the remaining 45 patients, the mean +/- SD iron dose that was given was 1,075 +/- 269 mg. The mean +/- SD elevation of hematocrit and hemoglobin on week 4 was 4.9 +/- 1.9% and 1.7 +/- 0.8 g/dl, respectively. Hematopoietic response was observed in 23 of 45 patients (51.1%). CONCLUSION: Total parenteral iron replacement with LMW iron dextran is an easy, safe, and effective alternative method for treating iron deficiency anemia in IBD. Harmless adverse reactions may develop in a minority of patients.

Genetic risk factors in young patients with ischemic colitis.

BACKGROUND & AIMS: Although ischemic colitis (IC) usually occurs in old people with concomitant illnesses, an increasing frequency of this disease among young people has been reported. Inherited risk factors have been suggested to play an important role in the pathogenesis of IC. The aim of this study was to investigate the prevalence and possible role of mutations associated with cardiovascular morbidity in young patients with IC. METHODS: Patients younger than 55 years old with nonocclusive colon ischemia who were conservatively treated were included in the study. The diagnosis of definite IC was based on established clinical, endoscopic, and histologic criteria. Twelve polymorphisms of thrombophilic and vasoactive genes were evaluated in a group of 19 young patients with IC compared with 52 matched healthy controls (HC) by using commercially available kit. RESULTS: The frequency of the 506 Q allele of the factor V (FV) 506 RQ (Leiden) mutation was significantly higher in patients with IC than in HC (P = .005). The allele frequency of the mutant 4G allele of plasminogen activator inhibitor (PAI) polymorphism was significantly higher in patients with IC compared with HC (P = .006). The frequencies of the genotypes and mutant alleles of the other 10 polymorphisms were not statistically different in the 2 groups (P > .05). CONCLUSIONS: Our results suggest that FV R506Q and PAI-1 gene polymorphisms might be associated with the development of IC in young patients without other serious illness. Genetic predisposition might play an important role in the pathogenesis of IC in young patients.

Association between thrombocytosis and iron deficiency anemia in inflammatory bowel disease.

BACKGROUND: Thrombocytosis and iron deficiency anemia are frequent complications of inflammatory bowel disease (IBD). The aim of this study was to investigate the correlation between iron deficiency anemia and thrombocytosis in IBD patients. METHODS: A total of 198 consecutive IBD patients and 102 healthy controls participated in the study. The parameters investigated were: platelets (PLT), mean platelet volume, platelet distribution width, plateletcrit, hematocrit (HCT) levels, hemoglobulin (Hb) levels, mean corpuscular volume (MCV), red cell distribution width (RDW), ferritin levels, soluble transferrin receptor (sTfR) levels, the sTfR-F index (sTfR-F=sTfR/log10 ferritin), and vitamin B12 and folate levels. Thrombocytosis was defined as an absolute number of PLT greater than 400k/µl. Disease activity indices (Crohn's Disease Activity Index for Crohn's disease and Simple Clinical Colitis Activity Index for ulcerative colitis) as well as C-reactive protein (CRP) were also correlated with the study parameters. RESULTS: The IBD patients demonstrated decreased HCT levels, Hb levels, MCV, mean platelet volume, and ferritin levels and an increased absolute PLT count, RDW, platelet distribution width, plateletcrit, sTfR and sTfR-F index (P<0.0001) compared with healthy controls. Twenty-seven patients exhibited thrombocytosis (13.6%). The median value for PLT (interquartile range) was 289 (228-355)k/µl, for Hb levels was 13.4 (12.0-14.7) g/dl, for ferritin levels was 36.6 (19.7-80.7) ng/ml, and for sTfR-F was 0.82 (0.61-1.37) mg/l. The PLT in IBD patients correlated with HCT levels, Hb levels, MCV, RDW, Fe levels, ferritin levels, sTfR, sTfR-F, CRP levels, Simple Clinical Colitis Activity Index, and Crohn's Disease Activity Index (Spearman's ρ correlation). In the multivariate analysis, only Hb levels, RDW, CRP levels, ferritin levels, and sTfR-F remained significant (P<0.05). None of the aforementioned was observed in the control group. CONCLUSION: The absolute PLT count seems to correlate with iron deficiency anemia parameters and disease activity in IBD patients. Controlling the inflammation and managing iron deficiency could lead to reversal of thrombocytosis in IBD patients.

Klippel-Trénaunay syndrome, pregnancy and the liver: an unusual interplay.

Klippel-Trénaunay syndrome is a rare congenital syndrome characterized by capillary malformations, soft tissue and bone hypertrophy, and varicose veins. There is a well-established risk for thrombotic complications in these patients. A case of a young patient diagnosed post partum with the very rare liver involvement is presented. The complex clinical course, the multidisciplinary management and the long-term outcome are discussed.

Diagnosing anemia in inflammatory bowel disease: beyond the established markers.

The main types of anemia in inflammatory bowel disease (IBD) are iron deficiency anemia (IDA) and anemia of inflammatory etiology, or anemia of chronic disease (ACD). In the management of IBD patients with anemia it is essential for the physician to diagnose the type of anemia in order to decide in an evidence-based manner for the appropriate treatment. However, the assessment of iron status in IBD in many cases is rather difficult due to coexistent inflammation. For this assessment several indices and markers have been suggested. Ferritin, seems to play a central role in the definition and diagnosis of anemia in IBD and transferrin, transferrin saturation (Tsat), and soluble transferrin receptors are also valuable markers. All these biochemical markers have several limitations because they are not consistently reliable indices, since they are influenced by factors other than changes in iron balance. In this review, in addition to them, we discuss the newer alternative markers for iron status that may be useful when serum ferritin and Tsat are not sufficient. The iron metabolism regulators, hepcidin and prohepcidin, are still under investigation in IBD. Erythrocytes parameters like the red cell distribution width (RDW) and the percentage of hypochromic red cells as well as reticulocyte parameters such as hemoglobin concentration of reticulocytes, red blood cell size factor and reticulocyte distribution width could be useful markers for the evaluation of anemia in IBD.

Soluble transferrin receptor-ferritin index in the evaluation of anemia in inflammatory bowel disease: a case-control study.

BACKGROUND: No reliable biochemical markers exist for the differentiation between iron deficiency anemia (IDA) and anemia of chronic disease (ACD) in the setting of inflammatory bowel disease (IBD). The aim of this study was to investigate the use of soluble transferrin receptor (sTfR) and sTfR-ferritin (sTfR-F) index in the evaluation of anemia in patients with IBD. METHODS: One hundred IBD patients [49 ulcerative colitis (UC), 51 Crohn's disease (CD)] and 102 healthy controls were enrolled. Serum levels of ferritin, transferrin saturation and sTfR were analyzed in all patients and controls. sTfR-F index was calculated based on the ratio: sTfR/ log ferritin. The value of sTfR and sTfR-F for diagnosis of IDA was assessed. RESULTS: Forty two IBD patients (41% of UC and 42.9 % of CD) fulfilled the WHO criteria for the diagnosis of anemia. Among them thirty (30 %) had IDA, four (4%) had ACD and eight (8%) had mixed IDA/ACD. Patients with IDA had significantly higher sTfR and sTfR-F index levels compared with those without IDA (P<0.0001). Both sTfR and sTfR-F index were not correlated with CRP levels or disease activity. High sTfR levels (>1.8 mg/L) had sensitivity 81% and specificity 80%, whereas high sTfR-F index (>1.4) had sensitivity 91% and specificity 92% for the diagnosis of IDA. CONCLUSION: These results suggest that the sTfR-F index seems to be very efficient in the detection and diagnosis of IDA, among patients with IBD.

Measurement of reticulocyte and red blood cell indices in the evaluation of anemia in inflammatory bowel disease.

BACKGROUND: The commonest types of anemia in inflammatory bowel disease (IBD) are iron deficiency (IDA) and anemia of chronic disease. The differentiation between these two conditions is important for the management of the patient. The aim of this study was to investigate the usefulness of reticulocyte and red blood cell indices in the evaluation of anemia in IBD. METHODS: One hundred IBD patients [49 ulcerative colitis (UC), 51 Crohn's disease (CD)] and 102 healthy controls were enrolled. Measurement of reticulocyte and red blood cell indices was performed using the Coulter LH780 Hematology Analyzer (Beckman Coulter). Additionally, serum levels of ferritin, transferrin saturation (Tsat) and soluble transferrin receptor (sTfR) were analyzed in all patients and controls. RESULTS: The prevalence of anemia was 41.2% for UC and 42.9% for CD, whereas 30 IBD patients (30%) had IDA. Red cell Distribution Width (RDW), Red blood cell Size Factor (RSF), and Reticulocyte Distribution Width-Coefficient of Variation (RDWR-CV) were found significantly correlated with both Tsat and sTfR but not with ferritin levels. Patients with IDA had significantly higher RDW and RDWR-CV and significantly lower RSF levels compared with those without IDA. High values of RDW (sensitivity 93%, specificity 81%) and low values of RSF (sensitivity 83%, specificity 82%) were the best markers for the diagnosis of IDA. Both RDWR-CV and RDWR-SD were significantly correlated with disease activity and CRP levels. CONCLUSION: RDW, RSF and RDWR, could be useful markers for the evaluation of anemia and disease activity in IBD.

Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease.

BACKGROUND: Anemia is an important complication of inflammatory bowel disease (IBD). Recent data suggest that hepcidin is a major mediator of anemia with a central role in iron homeostasis and metabolism. The aim of this study was to evaluate the serum levels of hepcidin and its prohormone, prohepcidin, in patients with IBD in comparison with healthy controls. METHODS: One hundred patients with IBD [49 ulcerative colitis (UC), 51 Crohn's disease (CD)] and 102 healthy controls were enrolled. Serum hepcidin and prohepcidin levels were measured by commercially available enzyme-linked immunosorbent assays kits. Their relationship with clinical and laboratory parameters of UC and CD was assessed. RESULTS: Median hepcidin levels were significantly higher in both patients with UC and patients with CD compared with healthy controls (P<0.0001). Median prohepcidin levels were significantly lower in patients with IBD compared with healthy controls (P = 0.03). In the univariate analysis, serum hepcidin was significantly negatively correlated (r = -0.36, P = 0.0003), whereas serum prohepcidin was positively correlated (r = 0.65, P<0.0001) with the hemoglobin levels. Significant correlations of both hepcidin (r = 0.34, P = 0.0007) and prohepcidin (r = -0.21, P = 0.04) with ferritin levels were found in patients with IBD. Serum hepcidin was also correlated with disease activity (for UC, r = 0.36, P = 0.009) and C-reactive protein (r = 0.29, P = 0.004). After multivariate analysis serum hepcidin levels remained significantly correlated with ferritin (P = 0.0008) and disease activity (for UC, P = 0.004). CONCLUSION: Serum hepcidin and prohepcidin levels are significantly altered in patients with IBD compared with healthy controls. This finding suggests a substantial role of these two hormones in the development of anemia in IBD.

Effects of tumor necrosis factor alpha inhibition with infliximab on lipid levels and insulin resistance in patients with inflammatory bowel disease.

INTRODUCTION: TNF-alpha is a critical mediator of inflammation with an important role in metabolic profile and insulin resistance. The regulation of these parameters by TNF-alpha in inflammatory bowel disease (IBD) is, however, poorly understood. The aim of this study was to assess the in-vivo TNF-alpha-mediated regulation of insulin resistance and of lipid levels in patients with IBD. METHODS: Twenty-two patients with IBD (eight females; 19 Crohn's disease) received infliximab according to treating physician's assessment at weeks 0, 2 and 6 from baseline and subsequently every 8 weeks and were prospectively followed for 14 weeks. Fasting insulin, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A1 (apo-A1), apolipoprotein B100 and lipoprotein a were measured in serum at baseline and at week 14. Insulin resistance was calculated with the use of the Homeostasis Model Assessment index. RESULTS: Infliximab therapy induced clinical response or remission in 19 of the 22 patients. C-reactive protein levels were significantly decreased by week 14. Body mass index was increased in all patients. No difference was observed in insulin levels, Homeostasis Model Assessment index, triglycerides, LDL cholesterol, apolipoprotein B100 and lipoprotein a. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels were significantly increased from baseline. CONCLUSION: TNF-alpha inhibition does not alter insulin resistance in IBD patients. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels are significantly increased after infliximab treatment compared with baseline. The importance of these alterations needs to be clarified in future studies.

Remifentanil compared with midazolam and pethidine sedation during colonoscopy: a prospective, randomized study.

PURPOSE: The objective of our study was to compare the safety and efficacy of remifentanil during colonoscopy with those of the standard combination of midazolam and pethidine. METHODS: One-hundred and sixteen consecutive patients scheduled for colonoscopy were randomly assigned to groups A or B. Patients in group A (n = 56) received intravenous (IV) midazolam and pethidine. Patients in group B (n = 60) received IV remifentanil. RESULTS: Recovery was faster in group B (0 min) than in group A (56 +/- 11.3 min) (P < 0.001). There was a marked difference between groups B and A with regard to the time of hospital discharge-28.7 +/- 4.3 and 148.9 +/- 34 min, respectively (P < 0.001). Patients in group A rated the procedure as comfortable, as also did those in group B. A combination of midazolam and pethidine had a greater affect on patients' cardiorespiratory characteristics. CONCLUSION: Remifentanil during colonoscopy provides sufficient pain relief with better hemodynamic stability, less respiratory depression, and significantly faster recovery and hospital discharge than moderate sedation with midazolam and pethidine.

A prospective, randomized comparison of adrenaline injection in combination with detachable snare versus adrenaline injection alone in the prevention of postpolypectomy bleeding in large colonic polyps.

OBJECTIVES: Our study sought to compare the efficacy of adrenaline injection in combination with detachable snare versus adrenaline injection alone in the prevention of postpolypectomy bleeding in large colonic polyps. METHODS: At the time of colonoscopy, patients with at least one colonic polyp > or =2 cm were randomized to receive treatment either by the injection of a 1:10.000 solution of adrenaline and the position of a detachable snare followed by a conventional snare polypectomy (group A) or injection of adrenaline followed by a conventional snare polypectomy (group B). A total of 159 consecutive patients were randomly assigned to one of the above groups. Out of them, 84 patients (47 men, 37 women, mean age 61 yr) were assigned to group A and 75 (37 men, 38 women, mean age 64 yr) to group B. Early (<24 h) and late (>24 h-30 days) bleeding complications were assessed. RESULTS: Overall bleeding complications occurred in 10/159 (6.2%) of the patients. There were two cases of bleeding in group A (2.3%), and eight in group B (10.6%) (P= 0.04). The number of early bleeding episodes was significantly reduced in group A patients (1 case) compared to that of group B (7 cases) (P= 0.02). In contrast, there was no significant difference between group A and B as far as late bleeding is concerned. CONCLUSIONS: Our data suggest that the use of adrenaline injection in combination with detachable snare may significantly decrease the number of early postpolypectomy bleeding episodes in patients with large colonic polyps.