Midkine level may be used as a noninvasive biomarker in Crohn's disease

Background/aim: Crohn's disease (CD) is a kind of inflammatory bowel disease. Midkine (MDK) is an endogenous inflammatory marker. We aimed to investigate the relationship between MDK levels and inflammation and hence determine whether MDK can be used as a noninvasive biomarker in active CD. Materials and methods: Sixty-five consecutive patients over the age of 18 with CD and 36 healthy controls were included in this study. CD patients' venous blood samples were taken before treatment. Serum MDK levels were determined in human plasma samples by enzyme-linked immunosorbent assay (ELISA) method. Results: The mean age of the study patients was 44.8 ± 12.5 years, 35 patients were female, and 30 were male. Of these 65 patients, 37 had active CD and 28 were in the remission phase. MDK levels were significantly higher in active and remission CD than in healthy controls (P = 0.01, P = 0.038, respectively). Conclusion: e report that there is an association between MDK levels and CD activation, and therefore with enhanced inflammation. MDK levels were significantly correlated with inflammatory indices. In line with our findings, we suggest the theory that MDK inhibitors may be useful in treating Crohn's disease.

Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis.

Objective Patients with ulcerative colitis (UC) are at an increased risk for thromboembolic events, particularly in patients with extensive and active disease. To date, a few studies have been published on the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in UC. However, there are no reports in the literature investigating the effect of UC treatment on plasma TAFI levels. Methods The plasma TAFI antigen levels were quantitatively determined using ELISA kits for 20 UC patients at activation and remission, along with 17 healthy controls. The association between the TAFI levels and inflammatory markers was assessed to determine UC activation. To predict and determine the activation of UC, the Truelove-Witts index and the endoscopic activation index (EAI) were used for each subject. Results The plasma TAFI levels were higher in UC patients at activation of the disease compared with the remission state and in healthy controls. Spearman's correlation analyses revealed that the WBC (r: 0.586, p<0.001), hsCRP (r: 0.593, p<0.001) and EAI (r: 0.721, p<0.001) were significantly correlated with the TAFI levels. The overall accuracy of TAFI in determining UC activation was 82.5% with a sensitivity, specificity, NPV and PPV of 80%, 85%, 81% and 84.2%, respectively (cut-off value: 156.2% and AUC: 0.879). Conclusion The present study demonstrates that the TAFI levels are elevated in the active state of UC. The assessment of TAFI levels in patients with UC in conjunction with other markers of inflammation may provide additional information for estimating UC activation and severity.

Seasonal clustering in inflammatory bowel disease: a single centre experience.

BACKGROUNDS AND AIMS: External stimuli are considered as possible triggers for the onset of inflammatory bowel disease (IBD), and particularly chronic ulcerative colitis (CUC) in genetically susceptible individuals. Our aims were to investigate monthly clustering-patterns in the onset of symptoms and diagnosis of IBD, as well as health seeking behavior in those individuals. MATERIALS AND METHODS: Two hundred and eighty-two consecutive patients with IBD were included. Onset of symptoms (month) and delay to diagnosis were analyzed. Kruskal-Wallis and Roger's test were used to analyze for statistical patterns in seasonal clustering. RESULTS: There were 181 males and 101 females with IBD; mean age: 40 ± 14.7 years (median: 38, range: 14-79 years). The peak number of IBD cases was seen in winter/early spring, with the lowest numbers in autumn, which reached statistical significance in the CUC group (p: 0.029). Seasonal changes were not significantly affected by gender. The time delay to diagnosis from symptom onset was 3.0 ± 2.3 months in males (median: 2, range: 0-12 months) vs 3.2 ± 3.2 months (median: 2, range: 0-18 months) in females (not statistically significant). CONCLUSION: Our results show a seasonal relation in IBD cases, particularly in CUC, which may suggest external stimuli acting as a precipitant to IBD in susceptible individuals. There was a delay between symptom onset and CUC diagnosis, which was not felt to be clinically significant.

MicroRNA expression profile in patients with stage II colorectal cancer: a Turkish referral center study.

BACKGROUND: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. MATERIALS AND METHODS: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). CONCLUSIONS: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

Nitric oxide is a potential mediator of hepatic inflammation and fibrogenesis in autoimmune hepatitis.

BACKGROUND: Despite advances in the understanding of the pathophysiological basis of autoimmune hepatitis (AIH), it is still difficult to delineate the mechanisms involved in progression from hepatic inflammation toward fibrosis. Our aim was to study serum concentrations of NO in AIH of different histological severity and possible effects of immunosuppressive therapy on NO production. MATERIALS AND METHODS: We studied serum NO metabolites (NOx) in 47 consecutive patients with AIH and in 28 age- and sex-matched controls. RESULTS: Serum NOx concentrations were higher in AIH patients than in controls (10.3 (4.5-27.3 µmol/L) vs. 4.3 (1.6-14.3 µmol/L), p < 0.001). According to liver histology, median NOx concentrations were significantly higher in patients with severe interface hepatitis compared to patients with mild-moderate interface hepatitis (12.3 (4.5-27.3 µmol/L) vs. 9.3 (4.6-20.3 µmol/L), p = 0.029). Similarly, serum NOx concentrations were significantly higher in patients with advanced fibrosis than in those with early fibrosis (12.2 (4.6-27.3 µmol/L) vs. 9.3 (6.6-12.8 µmol/L), p = 0.018). NOx concentrations decreased in 16 AIH patients who were tested also after biochemical remission was achieved (12.6 (4.5-22.8 µmol/L) at baseline and 5.9 (2.8-10.5 µmol/L) after remission, p = 0.001). CONCLUSION: This study shows that serum NOx levels are associated with the histological severity of AIH. Hepatocyte inflammation and injury may activate hepatic stellate cells and kupffer cells, and the consequences may include release of NO, which ultimately promotes hepatic fibrosis. Immunosuppressive therapy inhibits this process and the production of NO.

Characterization of de novo colonic stricture due to Crohn's disease.

BACKGROUND/AIMS: The development of colonic stenosis is a rare complication of Crohn's disease (CD) without a surgical anastomosis history. So, the management and long-term follow-up results of colonic stricture due to CD have not been clearly defined. In this study, we aimed to characterize de novo colonic stricture due to CD. MATERIALS AND METHODS: We evaluated 702 patients with CD to investigate colonic stricture. Colonic stricture was considered to exist when passage of a standard colonoscope was not possible and was diagnosed radiologically and endoscopically in this study. RESULTS: Of the 702 patients, 14 had colonic stricture according to the definition above. Of the 14, 8 were male. The interval between diagnosis of disease and recognition of the stricture varied from 0 to 13 years. Localization of the strictures differed from the rectum to cecum. Of the 14, 3 patients had more than 1 stricture. Pathological examination of the stricture(s) did not show dysplasia or malignancy initially or during the follow-up. CONCLUSION: De novo colonic stricture due to CD is a rare condition according to the presented study's results. Distribution of the stricture(s) varied from the rectum to cecum without increased colonic cancer risk. We observed the antifibrotic role of thiopurines and biologic agents in this study.

Safety of endoscopic ultrasonography in elderly patients: a single center prospective trial.

BACKGROUND AND AIMS: The aim of this prospective study is to evaluate the safety of both diagnostic and therapeutic endosonography (EUS) in geriatric population. METHODS: The study population, consisting of 222 patients who underwent endosonographic evaluation for different indications, was divided into two groups. Group I consisted of 165 patients, ≥ 65 years old; Group II consisted of 57 controls, <65 years old. The demographic information with clinical parameters, procedure medication used and complications was noted. RESULTS: The median age of Group I was 72 years (range 65-93 years) vs. 46 years (range 26-64 years) for Group II. Female-to-male ratio was 82/83 in Group I, while 32/25 in Group II. Pulse rate (84 vs. 89 beats/min, p = 0.024) and basal oxygen saturation (94 vs. 97 %, p < 0.001) levels were lower in Group I when compared with the control group, while systolic blood pressure measurements (150 vs. 130 mmHg, p < 0.001) were significantly higher in Group I. No cases of procedure-related bleeding, perforation and mortality were observed in both groups. CONCLUSION: Despite the well-known relative increased procedural risks, advanced age is not a contraindication for advanced endoscopic interventions. EUS can be regarded as a safe and effective procedure in ≥ 65 years old population.

Twice a day quadruple therapy for the first-line treatment of Helicobacter pylori in an area with a high prevalence of background antibiotic resistance.

BACKGROUND/AIMS: Bismuth-containing quadruple therapy given four times a day is effective in the first-line treatment of Helicobacter pylori. We aimed to investigate whether twice daily posology could eradicate H. pylori at a comparable rate in an area with a high prevalence of antibiotic resistance. MATERIALS AND METHODS: The study group consisted of 90 patients with treatment naïve H. pylori. Patients were randomized to BOMT1 group (Bismuth citrate 2 x 600 mg, omeprazole 2 x 20 mg, metronidazole 2 x 500 mg, tetracycline 2 x 500 mg; for 14 days) and BOMT2 group (Bismuth citrate 2 x 600 mg, omeprazole 2 x 20 mg, metronidazole 3 x 500 mg, tetracycline 4 x 500 mg; for 14 days). H. pylori eradication was assessed by both C14-urea breath test and stool antigen test at least 8 weeks after treatment. RESULTS: Demographic characteristics and endoscopy findings of the groups were similar. Eighty-two patients completed the study (BOMT1= 38 and BOMT2 = 44) including H. pylori eradication assessment. The eradication rates determined by PP and ITT analyses were 86.8% and 733% for BOMT1 group, 90.1% and 88.9% for BOMT2 group, respectively. BOMT1 was found to be non-inferior to BOMT2 treatment. Patients in BOMT2 group had a significantly higher rate of drug associated adverse events than BOMT1 (34.1% vs 9.3%; p = 0.008). CONCLUSIONS: Twice a day quadruple therapy is as effective as four times a day quadruple therapy in the first line treatment of H. pylori in a country with high resistance to metronidazole and clarithromycin and is more tolerable.

Atypical pANCA as a marker of indeterminate colitis for the prediction of ulcerative colitis and Crohn's disease.

AIM: The aim of this study was to demonstrate that the presence of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) in indeterminate colitis (IC) patients and the potential role of pANCA for predicting the patients either with ulcerative colitis (UC) or Crohn's disease (CD) for UC and CD. MATERIAL AND METHODS: Outpatients and inpatients from the hospital were retrospectively enrolled between April 2008 and December 2010. A total of 25 IC patients enrolled in the present study. Subsequently, 25 randomly selected serum samples were tested for pANCA in our laboratory. Determination of pANCA was performed by enzyme linked immunosorbent assay. RESULTS: Minimum follow-up was 12 months. The mean duration of disease was 20.52 months. The diagnosis was changed to UC in 13, to CD in 5 patients. The remaining 7 patients are still classified with IC, with mean disease duration of 21.29 months. Duration of disease differs statistically when comparing pANCA positive versus pANCA negative. A positive correlation was found between IC and disease location in our study. CONCLUSION: Patients with an initial diagnosis of IC who have positive serology are given a definitive diagnosis of UC or CD, respectively, more often than patients with negative serology.

Mean platelet volume is a useful indicator of systemic inflammation in cirrhotic patients with ascitic fluid infection.

AIM: Ascitic fluid infection (AFI) consists primarily of two variants, namely, culture-negative neutrocytic ascites and spontaneous bacterial peritonitis (SBP). Mean platelet volume (MPV) has begun to be used as a simple and inexpensive indicator of inflammation in some diseases. We aimed to analyse whether platelet size alterations would be useful in predicting AFI in cirrhotic patients. MATERIAL AND METHODS: A total of 135 patients with ascites due to cirrhosis and 55 control subjects were enrolled in this study. According to ascitic fluid analysis, 58 patients were considered to have AFI. MPV and inflammatory parameter values were determined for all study participants. The ability of MPV values to predict AFI in cirrhotic patients was analysed using receiver operator characteristic (ROC) curve analysis. RESULTS: A statistically significant increase in MPV levels was observed in cirrhotic patients with AFI compared to cirrhotic patients without AFI and healthy controls (p < 0.001). A statistically significant increase was observed in the AFI group with respect to MPV, C-reactive protein (CRP) and white blood cell (WBC) levels. ROC curve analysis suggested that the optimum MPV level cut-off point for cirrhotic patients with AFI was 8.45, with a sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of 70.7%, 67.5%, 75.4% and 62.1%, respectively (area under curve: 0.768). CONCLUSION: Our study shows that MPV is increased in cirrhotic patients with AFI. MPV measurement can considered to be an accurate diagnostic test in predicting AFI, possibly due to an ongoing systemic inflammatory response.

Serum nitric oxide levels in patients with benign and malignant biliary disease: a prospective single center study.

BACKGROUND: Despite advances in new diagnostic modalities, the differentiation of malignant from benign causes of biliary obstruction still remains difficult. The nitric oxide (NO) system is considered to be an important component in mediating cytokine activation of macrophages in inflammation. It also modulates tumorigenesis and regulates cell proliferation, angiogenesis, survival, and DNA repair. Although NO and its role in pancreatobiliary disorders has not been studied previously, the present study is designed to evaluate NO synthesis and metabolism in patients with biliary obstruction and to determine its usefulness in differentiating between benign and malignant causes of biliary obstruction. MATERIALS AND METHODS: Seventy-nine consecutive patients (60 malignant and 19 benign) with a history of biliary obstruction either with a benign or a malignant cause and 23 age-matched and sex-matched controls were included in this prospective study. NO metabolites, and conventional inflammation and tumor markers were determined. RESULTS: In patients with malignant biliary obstruction (MBO), serum NO metabolites were found to be significantly elevated (P<0.001). The receiver operating characteristic analysis showed that an NO level of 1.095 was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 78.3% and a specificity of 84.2% (area under the curve=0.821). Correlation analysis suggested that carbohydrate antigen 19-9 and carcinoembryonic antigen levels were correlated with NO levels for differentiating benign from malignant cause of biliary obstruction. CONCLUSIONS: Serum NO-associated tissue injury might be associated with the development of pancreatobiliary neoplasia by creating a local environment that is enriched with reactive oxygen species, cytokines, and other growth factors that may promote endothelial cell apoptosis. Moreover, serum NO levels may be used as an adjunctive marker to identify malignant causes of the obstructive jaundice.

Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis.

BACKGROUND AND AIMS: Liver biopsy is the gold standard procedure for documenting liver damage in chronic hepatitis C (CHC), as for many other chronic liver diseases. Mean platelet volume (MPV) is a laboratory marker obtained from complete blood count (CBC) analysers in routine clinical practice. The goal of the present study was to evaluate whether MPV would be useful in predicting liver histologic severity in CHC. PATIENTS AND METHODS: A total of 59 patients with CHC and 25 control subjects were recruited into the present study. There were 26 men and 33 women in the CHC group and 12 men and 13 women in the control group. MPV was recorded at the time of admission. The clinical characteristics of CHC patients, including demographics, laboratory and liver biopsy findings, were reviewed. RESULTS: A statistically significant increase in MPV values was observed in CHC patients (8.54 ± 0.63 fL) compared to healthy controls (7.65 ± 0.42 fL) (P < 0.001). Moreover, MPV values were significantly higher among patients with advanced fibrosis as compared to those with mild fibrosis (8.99 ± 0.57 fL vs. 8.19 ± 0.50 fL P < 0.001). Receiver operator characteristic (ROC) curve analysis suggested that the optimum cut-off point for MPV value in advanced fibrosis was 8.75 fL. (Sensitivity: 80.8%, specificity: 81.8%, positive predictive value [PPV] 77.8%, negative predictive value [NPV] 84.4%, accuracy 81.3%, AUC: 0.98 P < 0.001) CONCLUSION: The current study showed that MPV is increased in CHC with advanced fibrosis. Calculation of MPV along with the use of other markers may give further information about liver fibrosis severity in CHC.

The value of fecal calprotectin as a marker of intestinal inflammation in patients with ulcerative colitis.

BACKGROUND/AIMS: To assess intestinal inflammation, simple, inexpensive and objective tools are desirable in inflammatory bowel disease. This study aimed to evaluate fecal calprotectin as a marker of active disease in ulcerative colitis. MATERIALS AND METHODS: Sixty patients with a diagnosis of ulcerative colitis and 20 controls were recruited into the study. The disease activity of ulcerative colitis was determined by modified Truelove-Witts criteria and Rachmilewitz endoscopic index. The enzyme-linked immunosorbent assay was used to measure the concentrations of fecal calprotectin. C-reactive protein, erythrocyte sedimentation rate and hemogram were also measured, and inflammatory markers were compared with fecal calprotectin in determining disease activity. RESULTS: Fecal calprotectin concentration in the patients with active ulcerative colitis (n=30) was significantly higher than that in the inactive ulcerative colitis group (n=30) and in the controls (n=20) (95% confidence interval: 232.5 (0.75-625) vs 11.7 (0.2-625), 7.5 (0.5-512) mg/L, p<0.001). There was no significant difference between the patients with inactive ulcerative colitis and controls (p>0.05). The calprotectin concentration was greater in the patients with a more severe clinical index, higher endoscopic activity (>4), elevated C-reactive protein, leukocytosis, and extensive colitis (p<0.05). The areas under the curve of the receiver operating characteristics were 0.817, 0.809, 0.532, and 0.507 for C-reactive protein, fecal calprotectin, leukocyte count, and erythrocyte sedimentation rate, respectively. There was a significant correlation between the fecal calprotectin concentration and the endoscopic activity in ulcerative colitis (r = 0.548, p<0.001). CONCLUSIONS: Fecal calprotectin is a useful marker in the diagnosis of active disease and evaluation of clinical and endoscopic activity in ulcerative colitis.

Double balloon enteroscopy: a 3-year experience at a tertiary care center.

BACKGROUND/AIMS: To evaluate the indications, diagnostic yield, therapeutic interventions, complications and safety of double balloon enteroscopy (DBE) in clinical practice. METHODOLOGY: The medical records of the patients who underwent DBE at the Turkiye Yuksek Ihtisas Hospital between October 2007 and January 2010 were examined to note the demographic data, indications for the examination, results of previous non-invasive small bowel imaging and endoscopic procedures and the results of DBE including findings, endoscopic interventions, complications and pathological reports. RESULTS: A total of 139 procedures were performed in 118 patients. DBE was performed 81 times through mouth and 26 times through anus and additionally both approaches were used 16 times in the same patients. Panenteroscopy was successfully performed in 13 of 16 patients (87.5%) in whom it was attempted. The most common indication was obscure gastrointestinal bleeding (28.8%). DBE had an overall diagnostic and/or therapeutic contribution in 63 (53.4%) patients. The main pathologies detected on DBE were polyps (12.7%), infammation (10.7%) and vascular lesions (3.4%). Complications were recognized in four cases (3.4%) but no major complication occured. CONCLUSIONS: Our retrospective analysis showed that DBE is a useful, safe and well-tolerated method with a diagnostic and therapeutic impact for the management of small bowel diseases.

Assessment of neutrophil-lymphocyte ratio in ulcerative colitis: a promising marker in predicting disease severity.

BACKGROUND AND AIM: In order to diagnosis and monitor the disease activity of ulcerative colitis (UC), serum biomarkers are generally used, but none of them are specific for intestinal inflammation. It is therefore desirable in clinical practice to be able to assess disease activity with simple, inexpensive and objective tools. The objective of the present study was to assess whether the neutrophil-lymphocyte ratio (NLR) would be useful in predicting disease severity in UC patients who had not received corticosteroid or immunosuppressive drugs within a defined period of time. Additionally, a possible relationship of NLR with other inflammatory markers in UC patients was also investigated. METHODS: We designed a retrospective study examining the utility of NLR in estimating disease severity in UC patients admitted to our hospital between 2008 and 2011. In total, 119 patients with active UC and 77 patients with inactive UC were enrolled in the study group, and 59 age and gender matched healthy subjects were included as the control group. Disease activity was assessed using Truelove and Witts criteria. RESULTS: In the active UC group, NLR values were found to be elevated compared to inactive UC patients and controls (3.22 ± 1.29, 1.84 ± 0.69 and 2.01 ± 0.64, respectively). Using ROC statistics, a cut-off value of 2.16 indicated the presence of active disease with a sensitivity of 81.8% and a specificity of 80.5% (positive predictive value [PPV] 86.8%, negative predictive value [NPV] 73.8%). NLR values were found to be correlated with WBC and ESR levels. CONCLUSIONS: The present study revealed that NLR is increased in active UC. Peripheral blood NLR can reflect disease activity and can be used as an additional marker for estimating intestinal inflammation.