Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn’s colitis

Patients with indeterminate colitis (IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis (UC) or Crohn’s colitis (CC) which is not offered in 15%-30% of inflammatory bowel disease (IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry (MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as being either a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis.     

Crohn’s and colitis in children and adolescents

Crohn’s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn’s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn’s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn’s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.     

Refractory ulcerative colitis accompanied with cytomegalovirus colitis and multiple liver abscesses： A case report

Various hepato-biliary complications are an increased incidence in patients with inflammatory bowel disease, and portal bacteremia is well documented in patients with ulcerative colitis (DC). However, few reports mention UC in association with liver abscesses. Recently, there are several reports describing cytomegalovirus (CMV) infection in association with disease exacerbation and steroid refractoriness in patients with UC. Here we present a case of refractory UC accompanied with multiple liver abscesses and CMV colitis. The patient, a 72-year-old male, with a five-year history of repeated admissions to our hospital for UC, presented with an exacerbation of his UC. Sigmoidoscopy performed on admission suggested that his UC was exacerbated, then he was given prednisolone and mesalazine orally, and betamethasone enemas. However, he had exacerbated symptoms. Repeat Sigmoidoscopy revealed multiple longitudinal ulcers and pseudopolyps in the rectosigmoid colon. Although immunohistochemical staining of biopsy specimens and the serum testing for antigenemia were negative on admission and after the repeat Sigmoidoscopy, they became histologically positive for CMV. Nonetheless, the patient developed spiking fevers, soon after ganciclovir was administered. Laboratory studies revealed an increased white cell count with left shift, and Enterococcus fecalis grew in blood cultures. An abdominal computed tomography (CT) scan was obtained and the diagnosis of liver abscesses associated with UC was made, based on CT results. The hepatic abscesses were successfully treated with intravenous meropenem for 6 wk, without further percutaneous drainage. To our knowledge, this is the first reported case of multiple liver abscesses that develop during UC exacerbation complicated by CMV colitis.     

Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS: Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS: Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis.     

Heparin therapy for ulcerative colitis? Effects and mechanisms

Despite intensive medical treatment with steroids and immunosuppressants, acute colitis is still associated with a colectomy rate of up to 15%. Following the observation that a patient with severe steroid-resistant colitis went into remission when treated with heparin for a deep vein thrombosis, there have been a number of reports on the use of heparin in acute ulcerative colitis. Although small and uncontrolled, these studies consistently demonstrate the beneficial effects of heparin, with surprisingly few side-effects in a disease characterized by mucosal haemorrhage. The mechanisms by which heparin may ameliorate ulcerative colitis remain unclear. A simple anticoagulant effect may be responsible, but similar effects are not seen with warfarin. As a result of their intense negative charge, the glycosaminoglycans that constitute heparin have diverse biological effects. These include potent anti-inflammatory actions, in vitro and in vivo, and the potentiation of the activity of the peptide growth factors necessary for mucosal regeneration and repair. This review summarizes the clinical reports on heparin treatment for ulcerative colitis and explores the mechanisms by which this novel form of treatment may exert its effects.     

Ischemic colitis： Clinical practice in diagnosis and treatment

Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underestimated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable. The diagnosis is based on a combination of clinical suspicion, radiographic, endoscopic and histological findings. Therapy and outcome depends on the severity of the disease. Most cases of the non-gangrenous form are transient and resolve spontaneously without complications. On the other hand, high morbidity and mortality and urgent operative intervention are the hallmarks of gangrenous ischemic colitis.     

Postoperative management of ulcerative colitis and crohn’s disease

Approximately 10% to 30% of patients with ulcerative colitis and up to 70% of patients with Crohn’s disease will undergo surgery at some point during their lifetime. Although patients with ulcerative colitis are considered "cured" by surgery, patients who have undergone an ileal pouch anal anastomosis may develop pouchitis, cuffitis, pouch irritability, or even Crohn’s disease. Various therapies have shown success, including probiotics, in the prevention of pouchitis onset or relapse. Crohn’s disease historically recurs following surgery; prophylaxis against disease recurrence has been attempted with a variety of agents, with variable success. Innovative therapies holding promise for the future treatment or prevention of these conditions are under exploration.     

Medical therapies for ulcerative colitis and crohn’s disease

This review focuses on data reported in the last year on medical treatment of Crohn’s disease and ulcerative colitis. In Crohn's disease, a broad range of cytokine-based therapies are currently being tested. Although all are very exciting, the anti-tumor-necrosis-factor (TNF) approach remains the most effective, with infliximab (a chimeric monoclonal antibody directed against TNF) being the most active agent. With repeated infusions every 8 weeks, remission is induced and can be maintained even in refractory patients with no major apparent side effects. Thalidomide, an oral agent with anti-TNF effects, shows promise in noncontrolled experience. Important new data on azathioprine/ 6-mercaptopurine (6-MP) and its metabolites are also helpful. Methotrexate can induce remissions in 6-MP-allergic or refractory Crohn's patients and has now shown efficacy as a maintenance agent. Beneficial effects are also reported for a variety of new agents: mycophenolate mofetil, tacrolimus (FK506), growth hormone, and granulocyte colony-stimulating factor (G-CSF). Important observations in ulcerative colitis (UC) over the past year include evidence of a protective effect of 5-aminosalicylic acid (5-ASA) with respect to colorectal cancer, negative results from a study for heparin monotherapy, and results from a comparison of mycophenolate mofetil versus azathioprine as maintenance therapy. Epidemiologically, the negative association between appendectomy and UC was corroborated in a meta-analysis, suggesting an immunologic role for this organ. Finally, in chronic pouchitis, probiotic therapy was found to maintain remissions very significantly.     

Primary biliary cirrhosis and ulcerative colitis： A case report and review of literature

AIM: To summarize the characteristics of patients suffered from primary biliary cirrhosis associated with ulcerative colitis. METHODS: To report a new case and review the literature. RESULTS: There were 18 cases (including our case) of primary biliary cirrhosis complicated with ulcerative colitis reported in the literature. Compared with classical primary biliary cirrhosis, the patients were more often males and younger similar. The bowel lesions were usually mild with proctitis predominated. While ulcerative colitis was diagnosed before primary biliary cirrhosis in 13 cases, the presentation of primary biliary cirrhosis was earlier than that of ulcerative colitis in our new case reported here. The prevalence of primary biliary cirrhosis among patients of ulcerative colitis was almost 30 times higher than in general population. CONCLUSION: Association of primary biliary cirrhosis with ulcerative colitis is rare. It should be considered in the differential diagnosis of hepatobiliary disease in patients with ulcerative colitis, and vice versa.     

Positioning biologic therapy for Crohn’s disease and ulcerative colitis

Over the past decade, the introduction of biologic agents such as tumor necrosis factor-α and α4 integrin leukocyte adhesion molecule inhibitors has provided new and effective treatment options for patients with inflammatory bowel disease (IBD). Recent debates have centered on where biologics should be positioned within the current treatment strategy so as to maximize efficacy while balancing risk. This review highlights the current position biologics hold relative to conventional therapies within the current “step-up” treatment strategy. It also critically appraises emerging data, testing the hypothesis that positioning biologics early in the IBD treatment algorithm (“top-down” strategy) results in superior outcomes compared with the current step-up strategy, in which biologics are used only in patients failing conventional therapies or who are steroid dependent.     

Lansoprazole-associated collagenous colitis： Diffuse mucosal cloudiness mimicking ulcerative colitis

There have only been a few reports on lansoprazole-associated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimickin gulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis.Consequently sulfasalazine 2 g/d was started. The patient＇s diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Fivemonths later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea.Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.     

Efficacy of infliximab for luminal and fistulizing Crohn’s disease and in ulcerative colitis

Opinion statement Infliximab is arguably the first major advance in therapy for inflammatory bowel disease in more than a quarter of a century. Although it is important to distinguish efficacy from effectiveness, the data from clinical practice mirror those from randomized controlled trials. Infliximab has proven efficacious for luminal manifestations of Crohn’s disease (CD) regardless of location. It also has proven efficacy in the subset of penetrating disease to the skin and perianal area, and it increases rates of steroid-free remission. These benefits are reflected in improved quality of life, with limited data showing that infliximab can decrease rates of hospitalization and CD-related surgery. Infliximab also has proven to be efficacious in patients with ulcerative colitis (UC) and has increased rates of steroid-free remission. Whether infliximab will have an impact on the risk of colorectal cancer in UC and Crohn’s colitis has yet to be determined. The combination of strong evidence from large randomized controlled trials with substantial examination of use in the practice setting has moved biologic therapy with infliximab from novel to mainstream. In this review, the data for the efficacy of infliximab in controlled trials will be discussed in the context of real world effectiveness.     

Endoscopic surveillance in Crohn's disease and ulcerative colitis: who needs what and when?

Crohn's disease and ulcerative colitis are chronic inflammatory diseases resulting from an inappropriate innate and adaptive immune response towards commensal microbiota. Patients with Crohn's disease and ulcerative colitis carry an increased risk of developing colon cancer and/or small bowel carcinoma, respectively. The colorectal cancer risks of ulcerative colitis and Crohn's disease with comparable surface area involvement and disease duration are very similar. Early disease onset, disease extent, severity of inflammation, a family history of sporadic colorectal cancer, efficacy and duration of medical therapy, coexisting primary cholangitis and mucosal dysplasia are all risk factors for colorectal cancer. Regular endoscopic surveillance is endorsed by leading professional societies and outlined in guidelines and consensus statements. The yield of endoscopic surveillance, particularly to detect dysplasia, can be improved with chromoendoscopy with methylene blue dye spray-targeted biopsies, autofluorescence plus high-resolution endoscopy, chromoendoscopy-guided confocal laser microscopy and confocal laser microscopy in combination with narrow band imaging and high-resolution endoscopy. Proper bowel preparation, complete, careful inspection of the entire colon, a minimum withdrawal time and adherence to recommended management guidelines ensure a high-quality study and improve surveillance. Dysplasia can be graded by the Vienna or Riddell classification. Colectomy is recommended for patients with flat high-grade dysplasia confirmed by an expert gastrointestinal pathologist.