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Wedlake L.J.,Royal Marsden NHS Foundation Trust | Shaw C.,Royal Marsden NHS Foundation Trust | Whelan K.,Kings College London | Andreyev H.J.N.,GI Unit
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Radiotherapy-induced damage to noncancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option for the prevention and management of symptoms. Aim To synthesise the evidence for the use of elemental formula low- or modified-fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the gastrointestinal tract during pelvic radiotherapy. Methods Four electronic databases were searched. Randomised controlled trials (RCT), controlled trials (CT) and case series in adult patients receiving radiotherapy for pelvic cancers employing nutritional interventions to reduce gastrointestinal toxicity were included. Methodological quality was assessed using a bespoke tool. Results Twenty-two original studies (2446 patients) were identified. Study quality was highly variable with only 37% scoring ≥10 points (maximum 17: bespoke scale). Few studies assessed compliance with the intervention. End-points varied and included symptom scales (IBDQ, CTC, Bristol Stool and RTOG). Evidence from RCTs was weak for elemental, low- or modified-fat, fibre and low-lactose interventions with 1/4, 3/4, 1/2, 0/1 trials respectively reporting favourable outcomes. Evidence for probiotics as prophylactic interventions was more promising (4/5 favourable), but dose, strains and methodologies varied. Conclusions There is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula may be appropriate in severe toxicity. Probiotics offer promise, but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients. The methodological quality of nutritional intervention studies needs to be improved. © 2013 John Wiley & Sons Ltd.

Jain V.K.,GI Unit | Turner N.C.,Breast Unit | Turner N.C.,Institute of Cancer Research
Breast Cancer Research | Year: 2012

Activation of the fibroblast growth factor receptor pathway is a common event in many cancer types. Here we review the role of fibroblast growth factor receptor signalling in breast cancer, from SNPs in FGFR2 that influence breast cancer risk and SNPs in FGFR4 that associate with breast cancer prognosis, and potential therapeutic targets such as receptor amplification and aberrant autocrine and paracrine ligand expression. We discuss the multiple therapeutic strategies in preclinical and clinical development and the current and future challenges to successfully targeting this pathway in cancer. © 2012 BioMed Central Ltd.

Hearnshaw S.A.,NHS Blood and Transplant | Logan R.F.A.,University of Nottingham | Palmer K.R.,GI Unit | Card T.R.,University of Nottingham | And 2 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2010

Background Acute upper gastrointestinal bleeding (AUGIB) accounts for 14% of RBC units transfused in the UK. In exsanguinating AUGIB the value of RBC transfusion is self evident, but in less severe bleeding its value is less obvious. Aim To examine the relationship between early RBC transfusion, re-bleeding and mortality following AUGIB, which is one of the most common indications for red blood cell (RBC) transfusion. Method Data were collected on 4441 AUGIB patients presenting to UK hospitals. The relationship between early RBC transfusion, re-bleeding and death was examined using logistic regression. Results 44% were transfused RBCs within 12 hours of admission. In patients transfused with an initial haemoglobin of <8 g/dl, re-bleeding occurred in 23% and mortality was 13% compared with a re-bleeding rate of 15%, and mortality of 13% in those not transfused. In patients transfused with haemoglobin >8 g/dl, re-bleeding occurred in 24% and mortality was 11% compared with a re-bleeding rate of 6.7%, and mortality of 4.3% in those not transfused. After adjusting for Rockall score and initial haemoglobin, early transfusion was associated with a two-fold increased risk of re-bleeding (Odds ratio 2.26, 95% CI 1.76-2.90) and a 28% increase in mortality (Odds ratio 1.28, 95% CI 0.94-1.74). Conclusions Early RBC transfusion in AUGIB was associated with a two-fold increased risk of re-bleeding and an increase in mortality, although the latter was not statistically significant. Although these findings could be due to residual confounding, they indicate that a randomized comparison of restrictive and liberal transfusion policies in AUGIB is urgently required. © 2010 Blackwell Publishing Ltd.

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.

Andreyev H.J.N.,GI Unit | Wotherspoon A.,GI Unit | Denham J.W.,Calvary Materials Newcastle Hospital | Hauer-Jensen M.,University of Arkansas for Medical Sciences
Scandinavian Journal of Gastroenterology | Year: 2011

Background: Cancer therapies increasingly achieve cure, but result in chronic moderate or severe gastrointestinal side effects in millions of patients worldwide. Paradoxically, modern therapies threaten to increase the burden of chronic gastrointestinal toxicity, not reduce it. Aim. To define pelvic radiation disease. Methods. A reinterpretation of published data. Results. The lack of interest in patients with pelvic radiation disease is startling. Symptoms after radiotherapy are only a manifestation of new onset gastrointestinal physiological deficits induced by the radiotherapy. With proper diagnosis and treatment of these deficit(s), the symptoms are curable. Science suggests that much radiotherapy-induced gastrointestinal morbidity is preventable. Once the true nature of radiation injury is understood, straightforward solutions emerge and inaccurate dogmas can be discarded. Imprecise language is a fundamental barrier to progress in complex disorders. Conclusions. Radiation-induced gastrointestinal toxicity is bedeviled by inappropriate terminology, causing confusion, and myth which legitimizes inappropriate clinical behavior. We must address honestly the uncomfortable reality that doctors, sometimes do harm. Not to do so in an era where survivorship is a reality, will deny millions often with severe symptoms from "pelvic radiation disease", the care which will help them. © 2011 Informa Healthcare.

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