Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.     

Magnifying endoscopy is useful for tumor border diagnosis in ulcerative colitis patients

Background and aimsEndoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC.MethodsWe analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes.ResultsWe examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p > 0.99).ConclusionsME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.     

Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis

AIM To investigate of pediatric ulcerative colitis activity index(PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity(Mayo endoscopic score).METHODS We reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d(either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions(such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayoendoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed.RESULTS We identified 99 patients(53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity(62%), consideration of medication change(10%), assessment of medication efficacy(14%), and cancer screening(14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was "moderate-substantial" agreement between the two reviewers in assessing rectal Mayo scores(kappa = 0.54, 95%CI: 0.41-0.68). CONCLUSION Endoscopic disease severity(Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.     

Granulocytapheresis in the treatment of patients with active ulcerative colitis

In recent years, considering the role of inflammatory processes and the involvement of the immune system in ulcerative colitis, granulocytapheresis, a technique for removing circulating leukocytes and preventing their migration into the intestinal mucosa, has been proposed for the treatment of acute ulcerative colitis. Initially introduced for the treatment of patients who did not respond to conventional therapy only, this new therapy may become a useful and safe method to induce clinical remission in patients with acute disease. This article will review the clinical applications and issues concerning the use of granulocytapheresis in ulcerative colitis.     

Sporadic adenoma in ulcerative colitis: endoscopic resection is an adequate treatment

BACKGROUND AND AIMS: In studies with small numbers of cases, it has been shown that endoscopic resection of adenomas in ulcerative colitis represents adequate treatment. In a larger study cohort with more prolonged follow up, we assessed the reliability of this finding. METHODS: Between 1988 and 2002, 148 consecutive patients, mainly from private gastroenterologists' practices, with ulcerative colitis were diagnosed as having an adenoma. In 60 patients, histological diagnosis was established in biopsies and in 87 patients in polypectomy specimens; one patient underwent proctocolectomy following diagnosis. The outcome of these patients was analysed after a mean follow up period of 6.0 (3.63) years. RESULTS: Among 60 patients, surprisingly without endoscopic treatment, 48.3% developed ulcerative colitis associated neoplasia in the same colon segment (23.3% low grade intraepithelial neoplasia; 8.3% high grade intraepithelial neoplasia; 16.7% carcinoma). Among 87 patients undergoing polypectomy of the adenoma, follow up revealed colitis associated neoplasia in other segments of colon in 4.6% of cases. CONCLUSION: Development of adenocarcinomas in a total of 6.7% of the overall patient group, and in 2.3% of those undergoing polypectomy, indicates that biopsy based diagnosis of an adenoma in ulcerative colitis must be considered to mandate endoscopic resection of the lesion; 40% of affected patients did not receive any form of endoscopic removal of the lesion. This shows that the most recent guidelines are not followed in a considerable number of patients with ulcerative colitis in private practice in Germany. Although polypectomy of the adenoma represents adequate therapy, further regular follow up examinations are nevertheless necessary.     

Infliximab for hospitalized patients with severe ulcerative colitis

To evaluate the efficacy of infliximab in hospitalized ulcerative colitis (UC) patients refractory to intravenous corticosteroids. Treatment options for steroid-refractory UC patients are limited and include cyclosporine and colectomy. Although two recent studies (ACT I/II) demonstrate a benefit from infliximab in outpatients with moderate to severely active UC, the utility of infliximab in severe i.v. steroid-refractory UC is less clear. We report our open-label experience with infliximab in hospitalized UC patients at the University of Pittsburgh Medical Center. All hospitalized UC patients who had received infliximab were identified. Age, sex, extent of UC, duration of disease, concomitant medication, hospital course, and response to infliximab were recorded. Response to infliximab was defined as avoidance of colectomy and cessation of corticosteroids. There were 12 UC inpatients refractory to intravenous corticosteroids and subsequently treated with infliximab. Nine of the 12 patients (75%) failed to respond to infliximab and required a colectomy; median time to colectomy was 3 months. Three patients (25%) did respond to infliximab and were able to withdraw from corticosteroids. In this open-label analysis, infliximab was not effective for the majority of UC patients refractory to intravenous corticosteroids. Whether earlier use of infliximab would prevent the need for hospitalization and colectomy is uncertain.     

Surgical and medical treatment in patients with acute severe ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of the mucosa of the colorectum. The treatment of UC depends on the severity of symptoms and the extent of the disease. Acute severe colitis (ASC) occurs in 12–25% of patients with UC. Patients with ASC must be managed by a multidisciplinary team. Medically or surgically aggressive treatment is carried out with the final aim of reducing mortality. Intravenous administration of corticosteroids is the mainstay of the therapy. Medical rescue therapy based on cyclosporine or infliximab should be considered if there is no response to corticosteroids for 3 days. If there has been no response to medical rescue therapy after 4–7 days, the patient must undergo colectomy in emergency surgery. Prolonged observation is counterproductive, as over time it increases the risk of toxic megacolon and perforation, with a very high mortality rate. The best potential treatment is subtotal colectomy with ileostomy and preservation of the rectum. Emergency surgery in UC should not be seen as a last chance, but can be considered as a life‐saving procedure. Colectomies in emergency setting are characterized by high morbidity rates but the mortality is low.     

Cerebral sinus thrombosis associated with severe active ulcerative colitis

A 19-year-old man with severe active ulcerative colitis was admitted to our hospital where he was prescribed 80 mg prednisolone and underwent leukocytapheresis (LCAP). Two weeks after initiating therapy, his symptoms had not recovered. We administered cyclosporin via continuous intravenous infusion for 12 days. Although his clinical symptoms improved, he complained of severe headache. Immediate plain computed tomography (CT) and magnetic resonance imaging angiography (MRA) revealed extensive thrombosis in the superior sagittal sinus and right transverse sinus. We treated this condition with the anticoagulant agent, heparin, which prevents and can treat venous thrombosis. We report an occurrence of cerebral sinus thrombosis accompanying ulcerative colitis, where active anticoagulant therapy was useful.     

Oral cyclosporine in patients with active severe ulcerative colitis not responding to steroids.

Oral cyclosporine has been reported to be useful in inducing remission in patients with active severe ulcerative colitis who fail to respond to intensive steroid therapy. We present our experience of its use in six patients.     

Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis

BACKGROUND: The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well-established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2-(4-chlorobenzoylamino)-3[2-(1H)-quinolinon-4-yl] propionic acid}, a cytoprotective agent, has been reported to have anti-inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients. METHODS: Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti-inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa. RESULTS: At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)-1beta but not of IL-8, and an increased ratio of IL-1 receptor antagonist/IL-1beta in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side-effects were noted in any patients. CONCLUSION: Rebamipide enema therapy proved to be safe and useful in corticosteroid-refractory patients with the active distal type of UC.     

Tacrolimus induction followed by maintenance monotherapy is useful in selected patients with moderate-to-severe ulcerative colitis refractory to prior treatment

Background

Tacrolimus in refractory ulcerative colitis often serves as a bridge to long-term maintenance therapy with thiopurines. Our aim was to review efficacy and safety of tacrolimus in active ulcerative colitis resistant to conventional therapies, including anti-tumour necrosis factor.

Methods

Charts of consecutive outpatients with refractory ulcerative colitis, in whom tacrolimus was orally administered as a 12 week-induction (target trough levels 10–15 ng/mL) followed by a maintenance therapy (target trough levels 5–10 ng/mL), were retrospectively reviewed. Clinical remission and response at weeks 4, 12 and 52 as well as adverse events within 1-year therapy were reported.

Results

Twelve (40%) and six (20%) of the 30 patients included (14 males, mean age 37.1 ± 1.4 years) achieved a clinical remission and response, respectively, at week 12. Three responders to tacrolimus initiation experienced drug-related adverse events requiring discontinuation. Among the 18 remaining initial responders who tolerated tacrolimus, 8 (27%) were in clinical remission at week 52, whereas the remainder either experienced adverse events requiring drug withdrawal (n = 4) or relapsed (n = 6). Overall adverse events were recorded in 14 patients (46%), mainly finger tremor and urinary infections.

Conclusion

Oral monotherapy with tacrolimus may be a valuable long-term therapeutic option in selected patients with moderate-to-severe active refractory ulcerative colitis.     

Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission

BackgroundIt has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission.MethodsPatients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005–2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated.ResultsOne hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15–56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P = 0.048) or together with a past flare within the previous 12 months (P = 0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR = 7.5; IC95%; 1.8–29.9; P = 0.005).ConclusionsIn UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.     

Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis

BACKGROUND: Recently, granulocyte and monocyte adsorption apheresis (GCAP) has been shown to be safe and effective for active ulcerative colitis (UC). We analyzed the safety and efficacy of GCAP (G-1 Adacolumn) in patients with steroid-refractory and -dependent UC. G-1 Adacolumn is filled with cellulose acetate carriers that selectively adsorb granulocytes and monocytes/macrophages. METHODS: Forty-four patients with UC were treated with GCAP. These patients received 5 apheresis sessions over 4 weeks. Twenty patients had steroid-refractory UC (group 1) and 10 had steroid-dependent UC (group 2). Fourteen patients who did not want readministration of steroids were treated with GCAP at the time of relapse, just after discontinuation of steroid therapy (group 3). RESULTS: Of 44 patients treated with GCAP, 24 (55%) obtained remission (CAI < or = 4), 9 (20%) showed a clinical response, and 11 (25%) remained unchanged. Only 2 of 10 patients (20%) with severe steroid-refractory UC (CAI > or = 12) achieved remission, whereas 7 of 10 patients (70%) with moderate steroid-refractory UC achieved remission (p < 0.05). The dose of corticosteroids was tapered in 9 of 10 (90%) patients with steroid-dependent UC after GCAP therapy. Twelve (86%) of 14 patients in group 3 showed an improvement in symptoms and could avoid re-administration of steroids after GCAP. No severe adverse effects occurred. CONCLUSIONS: The findings of this study suggest that GCAP may be a useful alternative therapy for patients with moderate steroid-refractory or -dependent UC, although cyclosporin A or colectomy is necessary in patients with severe UC. GCAP may also be useful for avoiding re-administration of steroids at the time of relapse. Randomized, controlled clinical trials are needed to confirm these findings.