Clinical course and predictors of total colectomy in ulcerative colitis; a referral center experience from Turkey.

BACKGROUND/AIMS: We aimed to describe the clinical course of Ulcerative colitis (UC) and the factors that predict the need for total colectomy in Turkish patients with severe UC receiving regular follow up. MATERIALS AND METHODS: We analyzed the demographic and clinical characteristics of 612 patients with UC receiving regular follow up between 1994 and 2010 in a tertiary referral center in Ankara. RESULTS: Men accounted for 58% of patients (M:F ratio, 1.4:1), and the mean age at diagnosis was 37.9 years. Of these, 32% had distal colitis and 8.8% had further extension, and 39 patients (6.4%) had chronic active disease. Steroid dependency and steroid resistance rates were 7.5% and 17.2%, respectively. In multivariate analysis, steroid dependency (p=0.04), steroid resistance (p=0.002), further extension (p<0.001), presence of extensive disease (p=0.006), and chronic active disease (p<0.001) were independent predictors of the need for total colectomy. Patients with chronic active disease had lower total colectomy free survival (p<0.001). CONCLUSION: The predictors of total colectomy were comparable with those previously reported in the literature. However, we identified further extension in disease localization to predict the need for total colectomy.

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.

Colonic tuberculosis or Crohn's disease? An important differential diagnosis.

Abdominal tuberculosis can mimic any disease affecting the gastrointestinal tract such as infectious processes, tumors, periappendiceal abscess, and Crohn's disease. The differential diagnosis of Crohn's disease and intestinal tuberculosis is a dilemma to clinicians and pathologists as both are chronic granulomatous disorders with similar clinical features. Lower gastrointestinal bleeding is an infrequent presentation of both intestinal tuberculosis and Crohn's disease. Herein, we report a 56-year-old woman presenting with massive hematochezia due to isolated colon tuberculosis in whom the initial diagnostic work-up suggested Crohn's disease and review the current literature. Our report highlights the need for awareness of colonic tuberculosis in the differential diagnosis of massive hematochezia from Crohn's disease, especially before initiating treatment with immunosuppressive agents.

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.

Circulating CD4+CD25+ regulatory T cells in the pathobiology of ulcerative colitis and concurrent primary sclerosing cholangitis.

BACKGROUND: Immunopathogenetic features of primary sclerosing cholangitis (PSC) in ulcerative colitis (UC) still remains unclear. Peripheral blood CD4+CD25+ regulatory T cells have a key role in the induction and maintenance of peripheral self-tolerance and inhibit several organ-specific autoimmune diseases. Therefore, CD4+CD25+ T cells are believed to play an essential role in autoimmune diseases. The aim of the present study is to analyze the role of CD4+CD25+ T cells in the pathogenesis of UC-associated PSC. METHODS: This study evaluated the levels of CD4+CD25+ T cells in peripheral blood mononuclear cells (PBMC) of 27 UC patients with PSC and 20 UC patients as controls. CD4+CD25+ T cells were isolated from PBMC with a direct immunofluorescence technique, using mice monoclonal antibodies namely FITC-labeled anti-CD4 and PE-labeled anti-CD25. In each patient, CD4+CD25+ T cells percentage in PBMC were studied by flow cytometry, and then the number of CD4+CD25+ T cells were calculated. RESULTS: Twenty-seven UC patients with PSC and 20 UC patients without PSC as controls were enrolled in the present study. The percentage of CD4+CD25+ regulatory T cells among PBMC were significantly elevated in UC + PSC patients compared with UC patients without PSC (p = 0.04). CONCLUSIONS: CD4+CD25+ T cells were found to be elevated in UC patients with PSC suggesting a partial role of activated T cell response in the disease pathophysiology. Our findings imply that CD4+CD25+ regulatory T cells may play a key role in the immunopathogenesis of UC-associated PSC and may affect the therapeutic management of these diseases.

Comparison of demographic and clinical characteristics of patients with early vs. adult vs. late onset ulcerative colitis.

BACKGROUND & AIMS: There is limited data comparing influence of age on the presentation, clinical course, and therapeutic response of patients with ulcerative colitis. We aimed to compare the demographic and clinical characteristics of patients diagnosed with UC in older age vs. adulthood vs. early age. METHODS: Five-hundred sixty one patients with UC seen at our center from 1995 to 2011 were categorized into early onset (EO), adult onset (AO) and late onset (LO) due to age at date of initial diagnosis. Patients diagnosed younger than age 17 were defined as EO, while those diagnosed between 17 and 60 were defined as AO and older than age 60 as LO. All patients were analyzed for demographic and clinical characteristics. RESULTS: There was a male predominancy among LO patients (50% vs. 57.7% vs. 78.6%, p=0.004). Patients with EO UC were more likely to be non-smokers (p<0.001), and had higher family history of UC (p=0.02). Patients with EO UC had more steroid use (p=0.03), total colectomy (p=0.04), presence of chronic active disease (p=0.04) rates when compared with AO and LO groups. Patients in EO group had higher overall probability of surgery in 1, 5 and 10 years, when compared with patients in LO group (p=0.02), but it wasn't different between EO and AO groups (p=0.09). CONCLUSIONS: Our study showed that clinical course of UC was more aggressive in younger ages. Also the difference between the demographic characteristics suggests that different age groups have different risk factors for the disease development.

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.

MEFV gene mutations and its impact on the clinical course in ulcerative colitis patients.

Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa. The presence of gene responsible for FMF, MEFV, which frequently causes inflammation, may aggravate the clinical course of UC. We aimed to determine the prevalence of MEFV mutations in UC patients and its impact on the clinical course. Four groups were formed as group 1 UC with distal disease, group 2 UC with pancolonic disease, group 3 UC with total colectomy, and group 4 Rheumatoid Arthritis (RA) patients. Eleven mutations of FMF gene were investigated. The mean age of group 1, 2, 3, and 4 were 46.7 ± 13.9, 43.8 ± 12.9, 44.8 ± 14.2, and 45.8 ± 10.9 years, respectively. The mutations were identified in 19 of the 54 UC patients (35.2%). Homozygous E148Q in 2 patients (3.7%) and heterozygous in 17 patients (31.5%) (E148Q 11.1%, M694V 5.6%, V726A 5.6%, K695R 1.8%, M680I 1.8%, and compound heterozygous 5.6%) were determined. Frequencies of MEFV mutations in group 1, 2, and 3 were 30, 27.3, and 58.3%, respectively. The mutations were identified in 3 of the 20 RA patients (15%). All of them were heterozygous. The rate of MEFV mutations were higher in group 3 than in group 4 (P = 0.018), and the number of attacks that were treated with steroid in all UC patients with mutation positive was higher than in mutation negative (P = 0.016). FMF gene mutations may be identified in UC patients up to 58.3%. It may be suggested that the UC patients with severe form should be identified for MEFV mutations before the judgment of colectomy.

Low incidence of colorectal dysplasia and cancer among patients with ulcerative colitis: a Turkish referral centre study.

OBJECTIVES: To determine the incidences of dysplasia, adenomatous polyp and colon cancer in patients with ulcerative colitis (UC) and to evaluate the risk factors. MATERIAL AND METHODS: We retrospectively reviewed the medical records of patients with UC admitted to the Turkiye Yuksek Ihtisas Hospital between 1994 and 2008 and who subsequently developed colorectal cancer (CRC). RESULTS: Between 1994 and 2008, a total of 844 UC patients were followed in our clinic. A total of 275 patients entered our surveillance programme. The duration of UC was as follows: 10-15 years, n = 173 (62.9%); 15-20 years, n = 55 (20.0%); 20-25 years, n = 26 (9.5%), 25-30 years, n = 9 (3.3%); and > 30 years, n = 12 (4.4%). In terms of localization, 80 patients (29.1%) had distal disease, 107 (38.9%) had left-sided disease and 88 (32.0%) had extensive colitis. Adenomatous polyp was found in six patients (2.2%). Five cases (83.3% of the polyps) were in the diseased segment and one case (16.7%) was in the non-diseased segment. Endoscopy revealed dysplasia in 11 cases (4.0%). Of the 275 UC patients, CRC was diagnosed in only three (1.1%) during follow-up. Adenomatous polyp was not found in cases with colon cancer. CONCLUSIONS: In our cases with UC, rates of dysplasia and CRC were much lower than in other reports. The difference in rates may be explained by racial factors, specific environmental factors, intensive control of disease activity through medical therapy and effective colonoscopic surveillance programmes.

Value of fractional exhaled nitric oxide (FE NO) for the diagnosis of pulmonary involvement due to inflammatory bowel disease.

BACKGROUND: Pulmonary involvement due to inflammatory bowel disease (IBD) is frequent when evaluating a patient with IBD and pulmonary involvement remains complicated. Most of the patients are asymptomatic and the methods used are mostly invasive or expensive procedures. The aim of this prospective study is to evaluate the value of the fractional exhaled nitric oxide (FE(NO)) level for the diagnosis of pulmonary involvement due to IBD and to investigate any correlation between FE(NO) level and disease activity. METHODS: Thirty-three nonsmoker patients with IBD (25 ulcerative colitis [UC] and 8 Crohn's Disease [CD]) who were free of corticosteroid treatment and 25 healthy subjects as a control group were enrolled in this study. All patients with IBD were investigated for pulmonary involvement with medical history, physical examination, chest roentgenogram, oxygen saturation, blood eosinophil levels, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and FE(NO) level. RESULTS: Pulmonary involvement was established in 15 patients (45.5%) with IBD. The FE(NO) level was higher in patients with pulmonary involvement than without pulmonary involvement and healthy controls independent from the pulmonary symptoms, eosinophil count, duration of disease, activity of disease, and surgery history (FE(NO): 32 +/- 20; 24 +/- 8; 14 +/- 8 ppb, respectively) (P < 0.05). In addition, diffusion capacity (DLCO) was found to be significantly lower in patients with CD compared with UC (P < 0.05). CONCLUSIONS: This study showed that an increased FE(NO) level may be used for identifying patients with IBD who need further pulmonary evaluation.

Clinical features of ulcerative colitis and Crohn's disease in Turkey.

BACKGROUND AND AIMS: This study is aimed at determining the clinical and socio-demographic characteristics of Turkish patients with inflammatory bowel disease who have been treated in a tertiary referral center. PATIENTS AND METHODS: The study was conducted between 1993 and 2007 at Ankara Yuksek Ihtisas Hospital, Inflammatory Bowel Disease Clinics. The clinical and epidemiologic data from this clinic were gathered and analysed. RESULTS: During the study period, 702 patients were identified as having inflammatory bowel disease; among these, 507 with ulcerative colitis (72.2%) and 195 with Crohn's disease (27.8%). The mean age at diagnosis was 46.2 years in ulcerative colitis and 40 years in Crohn's disease (p < 0.001). The male to female ratio was 1.2 for ulcerative colitis and 1.6 for Crohn's disease (p = 0.12). Of the patients who were primarily diagnosed with ulcerative colitis 16.8% had their diagnoses changed to Crohn's disease after the follow-up period. CONCLUSIONS: Peak age of onset for both Crohn's disease and ulcerative colitis were similar to other countries. A slight male predominance of Crohn's disease and ulcerative colitis were found for Turkish patients. Though it takes longer to diagnose, Crohn's disease may have a milder course in Turkish patients.

Conscious sedation during endoscopic retrograde cholangiopancreatography: midazolam or midazolam plus meperidine?

BACKGROUND AND OBJECTIVE: No consensus exists for the safest and most effective agent and for optimal drug doses for sedation during endoscopic retrograde cholangiopancreatography (ERCP). We aimed to compare the efficacy of midazolam with that of midazolam+meperidine, which provided comfort for the patient during ERCP. MATERIALS AND METHODS: The patients were randomized to sedation with midazolam only (2.87+/-0.67 mg) (n=48, median age 55.54+/-14.66, 21 women, 27 men) or midazolam (1.82+/-0.71 mg) with meperidine (42.81+/-14.61 mg) (n= 48, median age 55.48+/-2.57, 20 women, 28 men). Procedure-related parameters and the efficacy of sedation as assessed by the endoscopist and the patients were compared. RESULTS: Prior endoscopic history, preprocedure anxiety scores, age, sex, baseline vital signs and type of interventions were similar in both groups. Sedation level, duration of procedure and recovery time were comparable in both groups. Sedation quality assessment scale was significantly higher in the midazolam with meperidine group. Degree of pain sensed during the procedure was significantly lower in the midazolam with meperidine group. Midazolam with meperidine group had better patient satisfaction. Twenty-four hours after the procedure, the degree of amnesia between both sedation groups was similar. The number of patients unwilling to repeat the procedure was distinctly higher in midazolam group. Development of hypoxia and arrythmia in the midazolam and midazolam with meperidine groups were comparable. Two patients in the midazolam group developed paradoxical agitation. CONCLUSIONS: Conscious sedation for ERCP can be successfully and safely achieved by using either only midazolam or a low dose of midazolam with meperidine. Adding of meperidine to midazolam resulted in better patient and endoscopist comfort.

Two cases of pericarditis associated with inflammatory bowel disease.

Extraintestinal manifestations are common complications of inflammatory bowel disease (IBD) whereas the association of cardiac disease with IBD is rarely reported. Cardiac manifestations may be diagnosed before, concomitantly or after the diagnosis of the specific type of inflammatory bowel disease. Pericarditis and myocarditis are potentially serious complications. This extraintestinal manifestation developed in one patient concomitantly with onset of intestinal disease. One patient had ulcerative colitis (UC), while other had Crohn's disease (CD). Indomethacin was effective in one and the other patient required prednisone in addition. Chest symptoms in patients with inflammatory bowel disease should be evaluated to exclude myopericardial disease.

Mucosal mast cells in irritable bowel syndrome and inflammatory bowel disease.

Even though exciting progresses have been until now, further studies are necessary to clearly understand the significance of MMC. Mast cells are thought to participate in the pathogenesis of inflammatory bowel disease and irritable bowel syndrome. However, their role in the pathogenesis remains unsettled. The specific aims of this study were to (1) examine mucosal mast cell counts in the cecum in patient with IBS, and IBD (2) compare MMC between the disease groups. We showed increased MMC count in IBS.

Intralesional steroid injection in benign esophageal strictures resistant to bougie dilation.

OBJECTIVE: Some benign esophageal strictures are highly resistant to bougie dilation. The aim of this study was to determine whether intralesional steroid injection had additional benefit to Savary-Gilliard's bougie dilation therapy (SGBD). METHODS: Twenty-one patients were treated with a bougie dilator. The patients were randomized into control and study groups. There were 11 patients in the control group (7 males, 4 females; mean age 45.09 +/- 24.64 years) and 10 patients in the study group (4 males, 6 females; mean age 49.40 +/- 16.49 years). The patients in the control group underwent only SGBD, but patients in the study group received an additional intralesional steroid injection (8 mg triamcinolone acetate into each quadrant). The number of dilations was divided by the follow-up period (in months) to determine the periodic dilatation index. RESULTS: There was no difference in age, sex, etiology, localization and recurrence of lesions, treatment outcome, complications and the number of dilations between the study and control groups. In the study group, the mean periodic dilatation index was 0.712 (range 0.097-2.75) and 0.289 (range 0-1) before and after injections, respectively (P = 0.03). Additionally, the mean number of dilations was 5.3 (range 2-11) and 1.6 (range 0-5) before and after injections, respectively (P = 0.03). The mean symptom-free interval was 24 +/- 12.75 months in the study group and 5.18 +/- 5.06 months in the control group (P < 0.001). The total periodic dilatation index was 0.193 +/- 0.123 in the study group, while it was 0.597 +/- 0.583 in the control group (P < 0.05). CONCLUSIONS: It can be concluded that intralesional steroid injections increase efficacy of bougie dilation and decrease the requirement for repetition of bougie dilatation.

Esophageal variceal ligation for acute variceal bleeding: results of three years' follow-up.

BACKGROUND/AIMS: Endoscopic variceal ligation is widely accepted as the optimum endoscopic treatment for esophageal variceal hemorrhage. However, the rebleeding course and long-term outcome of patients with esophageal variceal hemorrhage after ligation have been poorly defined. Therefore, we conducted a long-term follow-up study to delineate the outcome of ligation. METHODS: Twenty-one liver cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were treated by endoscopic variceal ligation. These patients received regular follow-up and detailed clinical assessment of at least 24 months. RESULTS: Twenty-one eligible patients were followed up for a mean of 44.45 months (range 33.5-64 months). The mean number of sessions required to obtain eradication was 3.57+/-1.99 (range 1-8). Esophageal varices could be obliterated within 11.57+/-6.8 weeks (range 3-30). The percentage of variceal recurrence during follow-up was 57.14% (12/21) after endoscopic variceal ligation. Recurrence were observed in a mean of 34 months (median 29 months). Rebleeding from esophageal varices appeared in four patients (19.04%). The appearance rates of portal hypertensive gastropathy and fundal gastric varices after varice obliteration were found to be 45.45% (5/11) and 25% (3/12), respectively. CONCLUSIONS: Based on the results of long-term follow-up of endoscopic variceal ligation, although the percentage of variceal recurrence was high, endoscopic ligation achieved variceal obliteration faster and in fewer treatment sessions. Furthermore, endoscopic variceal ligation had a lower rate of rebleeding and of development of fundal gastric varices, but high portal hypertensive gastropathy.