Sutton, United Kingdom
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Feagan B.G.,University of Western Ontario | Lemann M.,GI Unit | Befrits R.,Karolinska University Hospital | Connell W.,St Vincents Health | And 11 more authors.
Inflammatory Bowel Diseases | Year: 2012

Background: Symptom relief is the traditional treatment goal in Crohn's disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second-line treatments for severe, active CD. Certolizumab pegol is approved only in the U.S. and Switzerland as second-line treatment for moderate-to-severe, active CD. Data from trials of infliximab suggest that high-risk patients and patients with active inflammation (CRP elevation and/or ileocolonic ulcers) may benefit from earlier use of this drug. Methods: A Delphi survey was used to obtain consensus on issues surrounding bowel preservation and use of TNF antagonists. At the time of this survey, infliximab was the only TNF antagonist approved for the treatment of CD in Europe, Canada, and Australia. An expert panel of 12 gastroenterologists with substantial clinical experience using infliximab in clinical practice and trials in these areas participated. Results: The experts agreed that bowel preservation and mucosal healing are relevant and achievable goals, and form a rationale for using TNF antagonists in CD patients. Control of inflammation and induction of mucosal healing were considered essential for bowel preservation. Consensus areas: 1) mucosal healing is predictive of improved long-term disease course and increases the likelihood of steroid-free remission; 2) infliximab induces sustained mucosal healing, promotes bowel preservation, and reduces hospitalizations and surgeries; 3) benefits of infliximab in relation to mucosal healing, bowel preservation, and clinical remission increase when therapy is initiated earlier. Conclusions: Treatment with TNF antagonists helps preserve the bowel in CD patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.


Corleto V.D.,University of Rome La Sapienza | Corleto V.D.,Research Center etro | Pagnini C.,University of Rome La Sapienza | Pagnini C.,Research Center etro | And 9 more authors.
Digestive and Liver Disease | Year: 2010

Background: Several studies have tried to find possible associations between genetic polymorphisms and inflammatory bowel disease prevalence and/or phenotype. Our objectives were to test the frequency and phenotypic association of two polymorphisms of the interleukin-1 pathway, IL-1β-511 and IL-1RN*2, in inflammatory bowel disease patients and controls from an Italian population, and to compare our data with previously published similar studies in Europe. Methods: We screened 290 inflammatory bowel disease patients (178 ulcerative colitis and 112 Crohn's disease) and 106 controls for IL-1β-511 and IL-1RN*2 polymorphisms by polymerase chain reaction (PCR)-based methods. The prevalence of the IL-1β-511 and IL-1RN*2 polymorphisms in European inflammatory bowel disease patients was calculated by a meta-analysis of previously published studies using the Mantel-Haenszel method. Results: No correlation between the IL-1 polymorphisms and inflammatory bowel disease prevalence was found in our study population. Crohn's disease patients with the IL-1β-511 mutation had a higher rate of complicated disease. A trend for an association between the IL-1RN*2 mutation and a higher risk for inflammatory bowel disease has been found only in studies with Northern European populations. Conclusions: The IL-1β-511 mutation can be associated with complex disease behaviour in Italian Crohn's disease patients. The IL-1RN*2 mutation may play a role in Northern European people with inflammatory bowel disease. © 2009 Editrice Gastroenterologica Italiana S.r.l.


Wedlake L.J.,Royal Marsden NHS Foundation Trust | Thomas K.,Royal Marsden NHS Foundation Trust | Lalji A.,GI Unit | Blake P.,Royal Marsden NHS Foundation Trust | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: Significant chronic symptoms following pelvic radiotherapy occur more frequently than commonly realized. Predictive factors for the development of late symptoms are poorly defined. Moderate sustained acute (cumulative) toxicity might predict severe late effects better than peak reaction. Methods and Materials: To determine prospectively whether peak or cumulative gastrointestinal (GI) acute symptoms better predict late symptoms in patients receiving pelvic radiotherapy. Symptom scores were measured weekly from the start of radiotherapy, and at 1 year using the Modified Inflammatory Bowel Disease Questionnaire - Bowel subset. The possible prognostic impact of patient-related factors was explored. Results: Three hundred and eight patients were recruited. 100 were excluded due to lack of follow-up data at one year resulting from death, too ill, stoma, relapsed, non-response or withdrawal. A further 15 were excluded for incomplete data, leaving 193 patients with evaluable data. Of these, 28 had GI, 101 urological, and 64 gynecological cancers. Patients' median age was 65 years (range, 23-82), and they were treated with median 60 Gy dose for a median of 6 weeks. Univariate analysis revealed a significant association between cumulative acute symptom scores and scores at 1 year (p < 0.001), which was dose-independent (p < 0.001). Acute peak and 1-year scores were not associated (p = 0.431). The correlation coefficient between cumulative acute symptoms and symptoms at 1 year was 0.367 and for peak acute symptoms was weaker at 0.057. Patients with an abnormal body mass index and current smokers were more likely to experience worse symptoms at 1 year. Conclusion: Cumulative acute symptoms are more predictive of late symptoms than peak acute changes in score. This association is independent of the radiotherapy dose delivered and is suggestive of a consequential late effect. © 2010 Elsevier Inc.


Wedlake L.J.,Royal Marsden NHS Foundation Trust | Silia F.,GI Unit | Benton B.,GI Unit | Lalji A.,GI Unit | And 7 more authors.
European Journal of Cancer | Year: 2012

3-Hydroxy-methylglutaryl coenzyme-A reductase inhibitors (statins) improve survival following pelvic irradiation for cancer. Large studies suggest that patients with hypertension may have reduced gastrointestinal (GI) toxicity. Animal data suggest that statins and ACE inhibitors (ACEi) may protect against normal tissue injury. Their efficacy in humans has not been reported. Aims/methods: To evaluate the impact of statins and ACEi on normal tissue toxicity during radical pelvic radiotherapy. GI symptomatology was recorded prospectively before radiotherapy, weekly during treatment and 1 year later using the Inflammatory Bowel Disease Questionnaire - Bowel (IBDQ-B) subset. Cumulative acute toxicity (IBDQ-B AUC) and worst score were determined. Dose, brand and duration of statin and/or ACEi usage were obtained from General Practitioners. Results: Of 308 patients recruited, 237 had evaluable acute drug and toxicity data and 164 had data at 1 year. Acutely, 38 patients (16%) were taking statins, 39 patients (16.5%) were taking ACEi and 18 patients (7.6%) were taking statin + ACEi. Mean changes in acute scores were 7.3 points (non-statin users), 7.3 (non-ACEi users) and 7.0 (non-statin + ACEi users) compared to 4.8 points (statin users), 5.0 points (ACEi users) and 4.9 points (statin + ACEi users). Statin use (p = 0.04) and combined statin + ACEi use (p = 0.008) were associated with reduced acute IBDQ-B AUC after controlling for baseline scores (ANOVA). At 1 year, users maintained higher IBDQ-B scores than non-users in all user subgroups. Conclusion: Use of statin or statin + ACEi medication during radical pelvic radiotherapy significantly reduces acute gastrointestinal symptoms scores and also appears to provide longer-term sustained protection. © 2012 Elsevier Ltd. All rights reserved.


Andreyev H.J.N.,GI Unit | Davidson S.E.,Christie Hospital NHS Foundation Trust | Gillespie C.,Chelsea and Westminster Hospital | Allum W.H.,GI Unit | And 2 more authors.
Gut | Year: 2012

Backgound: The number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed. Methods: A multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments. Results: Different pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent and may also require specialist input. The largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy. Their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical treatments fail. All endoscopic and surgical interventions after radiotherapy are potentially hazardous as radiotherapy may induce significant local ischaemia. The best current evidence for effective treatment of radiation-induced GI bleeding is with sucralfate enemas and hyperbaric oxygen therapy. Conclusions: All cancer units must develop simple methods to identify the many patients who need help and establish routine referral pathways to specialist gastroenterologists where patients can receive safe and effective treatment. Early contact with oncologists and/ or specialist surgeons with input from the patient's family and friends often helps the gastroenterologist to refine management strategies. Increased training in the late effects of cancer treatment is required.


Sinha R.,GI Unit | Rawat S.,Ruby Hall Clinic
Indian Journal of Radiology and Imaging | Year: 2013

Aim: To assess the impact of an extended oral preparation magnetic resonance (MR) enterography protocol on bowel distension, timing of imaging, and the quality of diagnostic images. Materials and Methods: An analysis of 52 patients who underwent divided oral preparation and 39 patients who underwent standard preparation for MR enterography examination was done. Distension was assessed by measuring the transverse diameters of the jejunum, ileum, and the ileocecal region. Diagnostic quality of the examination was assessed subjectively by two radiologists and graded as poor, diagnostic, and excellent (Grades 1-3). Correlation between bowel diameter and diagnostic quality was assessed using regression analysis. Results: The mean diameters of the jejunum, ileum, and colon in patients who underwent divided preparation were 1.90 ± 0.47, 2.14 ± 0.41, and 4.27 ± 0.96 cm, respectively, and the mean diameters in patients who underwent standard preparation were 1.46 ± 0.47, 2.02 ± 0.47, and 4.45 ± 0.90 cm, respectively. A total of 96.6% of patients on divided dose had diagnostic distension of the bowel (Grades 2 and 3). A total of 87.9% of the patients on standard dose had diagnostic distension of the bowel (Grades 2 and 3). A greater number of patients who underwent divided preparation had diagnostic quality examinations compared to those given standard preparation (96.6% vs. 87.9%). A greater number of patients who underwent divided preparation had Grade 3 quality examinations compared to those on standard preparation (75.5% vs. 68.5%). There was significant difference between diagnostic (Grades 2 and 3) and optimal grades (Grade 3) of the jejunal diameters in patients having divided or standard preparation (89.7% vs. 66.6%, P < 0.05; 40.8% vs. 25%, P < 0.05, respectively). Linear regression showed a positive correlation between increasing bowel diameter and diagnostic grade of the examination (ρ = 0.76). Conclusion: Using an extended oral preparation with divided dose resulted in the majority of patients being scanned in a single visit to the MRI suite. Dividing the oral contrast into aliquots can promote uniform distension of the entire small bowel and provide better bowel distension and improve the diagnostic quality.


Szabo H.,Instituto Clinico Humanitas IRCCS in Gastroenterology | Fiorino G.,Instituto Clinico Humanitas IRCCS in Gastroenterology | Fiorino G.,GI Unit | Spinelli A.,University of Milan | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2010

Background The current therapies for Crohn's disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients' quality-of-life. Aim To summarize the published data regarding the potential anti-fibrotic role of drugs commonly used in CD and the most effective anti-fibrotic drugs used in other diseases evaluating their potential use to treat intestinal fibrosis in CD. Methods A literature search was performed in the PubMed, Medline, Cochrane and EMBASE databases, considering in vitro, animal and human studies on fibrosis in inflammatory bowel disease and other similar chronic pathologies. Results Treatment of fibrosis in CD is limited to surgery or endoscopic dilatation, although some of the drugs currently used may have anti-fibrotic activity. In other diseases, anti-fibrotic agents are already used or are in preclinical or clinical trials. ACE inhibitors, Angiotensin Receptor Blockers, and HMG-CoA inhibitors merit further investigation in CD because of their role in preventing fibrosis in cardiovascular and renal diseases. Conclusions Anti-fibrotic drugs are under evaluation or already used in clinical practice in other chronic inflammatory diseases. In CD, there is a great need for investigation into agents that may prevent, reduce or reverse intestinal fibrosis.


PubMed | GI Unit and Royal Marsden NHS Foundation Trust
Type: Journal Article | Journal: Clinical medicine (London, England) | Year: 2016

There is no national NHS tariff to fund services for patients experiencing long-term bowel and nutritional problems after cancer treatment. In this paper, we report the clinical characteristics and outcomes of patients referred to our service and the estimated cost of a completed episode of care. Patient characteristics, symptom severity, investigations, diagnoses, number of clinic visits and referrals elsewhere were recorded in a prospective cohort study. During 2013-14, 325 patients completed assessment and treatment. The majority of original cancer diagnoses were urological (43%) and gynaecological (21%). A median of six investigations were requested. 62% were found to have three or more new diagnoses including small intestinal bacterial overgrowth (46%), vitamin D deficiency (38%), bile acid malabsorption (28%), gastritis (22%), radiation-induced bleeding (20%), vitamin B12 deficiency (17%), pelvic floor weakness (17%), colorectal polyps (13%) and pancreatic insufficiency (5%). A median of three visits were required and all commonly reported gastrointestinal symptoms improved by discharge. The mean episode of care per patient was costed at 1,563. Effective amelioration of chronic gastrointestinal toxicity after cancer treatment costs substantially less than treating the cancer in the first place and requires an NHS tariff.


PubMed | University of Genoa, Pathology Unit, University of Perugia, University of Bologna and 8 more.
Type: Journal Article | Journal: United European gastroenterology journal | Year: 2014

The statements produced by the Consensus Conference on Diverticular Disease promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease (DD) in patients with uncomplicated and complicated DD were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas.


PubMed | University of Padua, Gastroenterology SOD2, Hospital Fatebenefratelli, Columbus University and 10 more.
Type: Journal Article | Journal: Journal of Crohn's & colitis | Year: 2016

Cancer risk in inflammatory bowel disease [IBD] is still debated. In a prospective, multicentre, nested case-control study, we aimed to characterise incident cases of cancer in IBD. The role of immunomodulators vs clinical characteristics of IBD as risk factors for cancer was also investigated.From January 2012 to December 2014, each IBD patient with incident cancer was matched with two IBD patients without cancer for: IBD type, gender, and age. Risk factors were assessed by multivariate regression analysis.IBD patients considered numbered 44619: 21953 Crohns disease [CD], 22666 ulcerative colitis [UC]. Cancer occurred in 174 patients: 99 CD [CD-K], 75 UC [UC-K]. Controls included 198 CD [CD-C], 150 UC [UC-C]. Cancer incidence in IBD was 3.9/1000, higher in CD (4.5/1000 [99/21,953]) than in UC (3.3/1000 [75/22,666]; p = 0.042). Cancers involved: digestive system [36.8%], skin [13.2%], urinary tract [12.1%], lung [8.6%], breast [8%], genital tract [6.9%], thyroid [4.6%], lymphoma [3.5%], others [6.3%]. In CD, penetrating behaviour and combined thiopurines and tumour necrosis factor alpha [TNF] antagonists were risk factors for cancer overall: odds ratio [OR] (95% confidence interval [CI] 2.33 [1.01-5.47]); 1.97 [1.1-3.5]; and for extracolonic cancers 3.9 [1.56-10.1]; 2.15 [1.17-4.1], respectively. In UC, risk factors were pancolitis and disease-related surgery for cancer overall (OR: 2.52 [1.26-5.1]; 5.09 [1.73-17.1]); disease-related surgery for colorectal cancer [CRC] (OR 3.6 [1.0-12]); and extensive and left-sided vs distal UC for extracolonic cancers (OR: 2.55 [1.15-5.9]; 2.6 [1.04-6.6]), respectively.In a multicentre study, penetrating CD and extensive UC were risk factors for cancer overall. Cancer incidence was higher in CD than in UC.

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