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.

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.

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.

Extension of ulcerative colitis.

BACKGROUND/AIMS: It is known that ulcerative proctitis might show extension, but in practice, patients with proctitis are not considered as important with regard to regular follow-up and treatment. The aim of this study was to evaluate the extension of ulcerative colitis cases limited to the rectum and compare them with the patients with rectosigmoid and left colonic ulcerative colitis for their features, risk factors influencing the extension and natural course of the disease. METHODS: The study involved 193 (62 rectal, 49 rectosigmoid and 82 left-sided) ulcerative colitis patients. RESULTS: Fourteen percent of the patients showed extension to at least one proximal segment in 3.9±2.9 (range: 0.8-12) years. The extension was found as 16.1% in proctitis, 12.2% in rectosigmoiditis and 13.4% in left-sided colitis groups. Extension was found 2.79-fold (95% confidence interval: 1.1-7.1) higher in patients with chronic active disease. Further, the patients with amoebic attacks, those under steroid treatment and those without treatment showed higher risk for extension. CONCLUSIONS: Patients with proctitis, like the patients presenting with more extensive colitis, should be offered regular treatment and follow-up.

Continuous active state of coagulation system in patients with nonthrombotic inflammatory bowel disease.

This study was planned for searching possible changes of the total coagulation and fibrinolysis system in inflammatory bowel disease (IBD) in order to obtain some clues for explaining the relation between IBD and hypercoagulability. A total of 24 patients with ulcerative colitis, 12 patients with Crohn disease, and 20 healthy controls were studied. Platelets; prothrombin time (PT); partial thromboplastin time (PTT); fibrinogen; D-dimer; fibrinogen degradation products; protein C; protein S; antithrombin; thrombin time; von Willebrand factor; coagulation factors V, VII, VIII, IX, XI, and XIII; plasminogen; antiplasmin; tissue plasminogen activator; plasminogen activator inhibitor 1; and prothrombin fragments 1 + 2 were studied. Most of the procoagulants (platelets, fibrinogen, von Willebrand factor, coagulation factor IX, and plasminogen activator inhibitor 1) were found increased together with decreases in some anticoagulants (protein S and antithrombin) in IBD. Also the activation markers of coagulation (D-dimer, fibrinogen degradation products, and prothrombin fragments 1 + 2) were all increased. The parameters of the total coagulation-fibrinolysis system were increased in IBD, regardless of the form and the activity of the disease.

Colovesical fistula as a complication of colonic diverticulosis: diagnosis with virtual colonoscopy.

A 65-year-old female patient admitted to our clinic with complaints of abdominal pain and watery diarrhea. She was diagnosed with colovesical fistula based on virtual colonoscopy findings. Since endoscopic and other radiological diagnostic tools were not able to establish a definite diagnosis, we found this case suitable for presentation.

Peripheral arthritis in the course of inflammatory bowel diseases.

BACKGROUND: Musculoskeletal disorders are well-defined extra-intestinal manifestations of inflammatory bowel diseases (IBD). There is little data regarding the frequencies of IBD and extra-intestinal manifestations from Central and East Europe and Middle Eastern countries. AIMS: To determine the prevalence of peripheral arthritis in IBD and to document the relationship to other extra-intestinal manifestations. METHODS: Enrolled in the study were 357 patients who were diagnosed with IBD from December 2002 through January 2008. All of the patients underwent a detailed whole-body examination by a gastroenterologist and rheumatologist. RESULTS: IBD-related peripheral arthritis (IBDPA) was found in 66 (18.5%) of the 357 patients (28.3% Crohn's disease, 13.5% ulcerative colitis; p=0.001 χ=11.62). IBDPA was more frequent in female patients (60.6 vs. 39.4%, p=0.000, χ=11.12). In eight (12.1%) cases, IBDPA occurred before the onset of IBD. Acute self-limiting episodes, recurrences of the attacks, and persistent symptoms of arthritis were present in 40 (60.6%), 26 (39.3%), and 29 (45.7%) patients, respectively. Arthritis was symmetrical in 33 (50%) cases. Knees (65.2%) and ankles (62.1%) were the most commonly affected joints. Erythema nodosum and pyoderma gangrenosum were more common among patients with IBDPA than patients without it (p=0.001, χ=10.49, and p=0.000 χ=25.77, respectively). CONCLUSIONS: IBDPA is a frequent extra-intestinal complication of IBD. Those of female gender and the presence of Crohn's disease, erythema nodosum and pyoderma gangrenosum have a higher risk to develop IBDPA.

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.

Natural anticoagulant protein levels in Turkish patients with inflammatory bowel disease.

Thromboembolism is an important cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate common thrombophilic markers in patients with IBD and to search for a relation between these predisposing factors and activity of disease. Seventy-four patients with ulcerative colitis, 22 patients with Crohn's disease and 20 healthy volunteers were enrolled into the study. Plasma levels of protein C, protein S, antithrombin III and activated protein C resistance were determined in patients with IBD and healthy controls. Mean values of protein C, protein S and antithrombin III were significantly lower in patients with ulcerative colitis and Crohn's disease compared with the healthy control group. Patients with active ulcerative colitis had lower protein C, protein S and antithrombin III level than patients in remission (P < 0.001, P < 0.001, P < 0.001). Levels of protein C, S and antithrombin III were also decreased in patients with active Crohn's disease compared with those in remission (P < 0.05, P < 0.001, P < 0.05). Differences in all natural anticoagulant levels between patients in remission and healthy individuals in both ulcerative colitis and Crohn's disease groups were not statistically significant (P > 0.05). No significant difference was observed in activated protein C resistance (APCR) between patients with active disease, those in remission and the control group (P > 0.05). Abnormalities in natural anticoagulants are common in patients with IBD during active disease.

Plasma transforming growth factor-beta1 level in inflammatory bowel disease.

BACKGROUND/AIMS: The aim of this study was to evaluate plasma transforming growth factor-B1 concentration in patients with inflammatory bowel disease at different stages of disease activation and to compare these values with those of healthy controls. METHODS: A total of 70 patients (31 women) evaluated in the Inflammatory Bowel Disease Clinics of TUrkiye YUksek Ihtisas Hospital, Gastroenterology Department, and 20 healthy controls (10 women) were enrolled in the study. Serum samples were obtained from 40 patients with ulcerative colitis (female/male: 18/22, mean age: 41.5+/-12), 30 patients with Crohn's disease (female/male: 17/13, mean age: 36.9+/-1.9) and 20 healthy controls (female/ male: 10/10, mean age: 32.1+/-1.7). The control group included normal blood donors without gastrointestinal complaints or a familial history of inflammatory bowel disease. Clinical activity in Chron's disease was measured by Crohn disease activity index and in ulcerative colitis patients by Rachmilewitz endoscopic index. Chron's disease patients with a Chron's disease activity index >150 and ulcerative colitis patients with a Rachmilewitz index > or =4 were accepted to have active disease. Determination of transforming growth factor-B1 level was performed with the enzyme- linked immunosorbent assay. RESULTS: Serum transforming growth factor-B1 levels were measured as: Chron's disease 1133.3+/-766.5 pg/ml, ulcerative colitis 1362.5+/-880.6 pg/ml and control group 1230.0+/-572.7 pg/ml. There were no significant differences between the three groups. In patients with active disease in ulcerative colitis, transforming growth factor-B1 level was measured as 1952.5+/-543.7, while this value was 772.5+/-750.5 in patientsin remission in ulcerative colitis. There was a significant difference between patients with active ulcerative colitis and remission ulcerative colitis. CONCLUSIONS: In inflammatory bowel disease, transforming growth factor-B1 can be used as a marker for differential diagnosis of active ulcerative colitis patients and remission ulcerative colitis patients. Nevertheless, more studies with larger patient groups are necessary.

Presence and diagnosis of amebic infestation in Turkish patients with active ulcerative colitis.

BACKGROUND: It is difficult to definitively diagnose acute amebiasis, particularly when this condition is superimposed on inflammatory bowel disease. Our goals in this study were to determine the prevalence of amebiasis in individuals with active ulcerative colitis, and to identify clinical and laboratory parameters that are of value for diagnosing amebiasis in this patient group. METHODS: The subjects were 111 patients (76 women, 35 men) with confirmed active ulcerative colitis who attended our hospital's Inflammatory Bowel Disease Outpatient Clinic between May 2002 and March 2006. In each case, a detailed medical history was collected, blood samples were tested for inflammatory markers, and stool samples were evaluated for presence of amebae using an Enzyme-Linked Immunosorbent Assay (ELISA) for detection of Entamoeba histolytica antigen. The clinical and laboratory variables for the ELISA-positive and ELISA-negative groups were compared. RESULTS: Amebiasis was detected in 35 (31.5%) of the subjects. Patient age, disease duration, endoscopic activity index, serum C-reactive protein level, and white blood cell count were not useful for diagnosing amebiasis in this patient group. CONCLUSIONS: Given the high rate of amebiasis observed in our patients with active ulcerative colitis, we recommend that, in Turkey any individual with ulcerative colitis who presents with symptoms of disease activation should be tested for ameba using antigen detection kits. A high index of suspicion is especially important in any region where E. histolytica is endemic.

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.