Publications
289 results found
van der Ploeg VA, Maeda Y, Faiz OD, et al., 2016, Standardising assessment and documentation of pouchoscopy, 11th Congress of European Crohn's and Colitis Organisation, Publisher: Oxford University Press (OUP), Pages: S146-S146, ISSN: 1876-4479
Lynch PM, Morris JS, Wen S, et al., 2016, A proposed staging system and stage-specific interventions for familial adenomatous polyposis., Gastrointestinal Endoscopy, Vol: 84, Pages: 115-125.e4, ISSN: 0016-5107
BACKGROUND AND AIMS: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. RESULTS: The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.
IJspeert JE, Rana SA, Atkinson NS, et al., 2015, Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis, Gut, Vol: 66, Pages: 278-284, ISSN: 1468-3288
OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.
Aziz O, Albeyatti A, Clark S, et al., 2015, When do Anastomotic Leaks Occur After Laparoscopic Total Colectomy and Ileo-rectal Anastomosis? A Case-Controlled Study in Patients with Familial Adenomatous Polyposis, International Surgical Congress of the Association of Surgeons of Great Britain and Ireland, Publisher: Wiley, Pages: 169-169, ISSN: 1365-2168
Landy J, Walker AW, Li JV, et al., 2015, Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis, Scientific Reports, Vol: 5, ISSN: 2045-2322
Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a “healthier” pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.
Lee GH, Hawkins J, Hyer W, et al., 2015, Ileal pouch anal anastomosis in pediatric familial adenomatous polyposis: A 24-year review of operative technique and patient outcomes.
Askari A, Nachiappan S, Murphy J, et al., 2015, Patients in England with inflammatory bowel disease (IBD) who develop colorectal cancer (CRC) have shortened survival when compared with patients with sporadic CRC, 2nd Digestive Disorders Federation Conference, Publisher: BMJ Publishing Group, Pages: A327-A328, ISSN: 0017-5749
Askari A, Nachiappan S, Murphy J, et al., 2015, Colorectal cancer (CRC) patients with inflammatory bowel disease (IBD) are at increased risk of poor outcomes post surgery in england, 2nd Digestive Disorders Federation Conference, Publisher: BMJ Publishing Group, Pages: A326-A326, ISSN: 0017-5749
Aziz O, Albeyatti A, Derias M, et al., 2015, A CASE-CONTROLLED STUDY DEMONSTRATING THAT CHANGES ASSOCIATED WITH RECTAL ANASTOMOTIC LEAKAGE ARE DETECTABLE WITHIN 48 HOURS OF SURGERY, 2nd Digestive-Disorders-Federation Conference, Publisher: BMJ PUBLISHING GROUP, Pages: A152-A152, ISSN: 0017-5749
Lynch PM, Burke CA, Phillips R, et al., 2015, An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis., Gut, Vol: 65, Pages: 286-295
BACKGROUND AND AIM: Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. METHODS: The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. RESULTS: 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). CONCLUSIONS: CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number N01-CN95040.
Lee GH, Malietzis G, Askari A, et al., 2015, Is right-sided colon cancer different to left-sided colorectal cancer? - A systematic review, EJSO, Vol: 41, Pages: 300-308, ISSN: 0748-7983
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- Citations: 271
Uppara M, Adaba F, Askari A, et al., 2015, A systematic review and meta-analysis of the diagnostic accuracy of pyruvate kinase M2 isoenzymatic assay in diagnosing colorectal cancer, World Journal of Surgical Oncology, Vol: 13, ISSN: 1477-7819
Background: Screening programmes exist in many countries for colorectal cancer. In recent years, there has been adrive for a non-invasive screening marker of higher sensitivity and specificity. Stool-based pyruvate kinase isoenzymeM2 (M2-PK) is one such biomarker under investigation. The aim of this systematic review and meta-analysis is todetermine the diagnostic accuracy, sensitivity and specificity of M2-PK as a screening tool in colorectal cancer.Methods: A literature search of Ovid Medline, EMBASE and Google Scholar was carried out. The search strategy wasrestricted to human subjects and studies published in English. Data on sensitivity and specificity were extracted andpooled. Statistical analysis was conducted using summary receiver operating characteristic (SROC) curve methodology.Results: A total of eight studies were suitable for data synthesis and analysis. Our analysis showed a pooled sensitivityand specificity for M2-PK to be 79% (CI 73%–83%) and 80% (CI 73%–86%), respectively. The accuracy of M2-PK was 0.85(0.82–0.88).Conclusion: Faecal M2-PK assay has a relatively good sensitivity and specificity and high accuracy for screeningcolorectal cancer.
Cheng THT, Gorman M, Martin L, et al., 2015, Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 23, Pages: 260-263, ISSN: 1018-4813
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- Citations: 12
Davis H, Irshad S, Bansal M, et al., 2015, Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche, Nature Medicine, Vol: 21, Pages: 62-70, ISSN: 1546-170X
Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.
Landy J, Al-Hassi HO, Ronde E, et al., 2014, Innate Immune Factors in the Development and Maintenance of Pouchitis, INFLAMMATORY BOWEL DISEASES, Vol: 20, Pages: 1942-1949, ISSN: 1078-0998
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- Citations: 10
Lee GH, Payne SJ, Melville A, et al., 2014, Genetic testing in inherited polyposis syndromes - how and why?, COLORECTAL DISEASE, Vol: 16, Pages: 595-602, ISSN: 1462-8910
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- Citations: 3
White I, Jenkins JT, Coomber R, et al., 2014, Outcomes of laparoscopic and open restorative proctocolectomy., Br J Surg, Vol: 101, Pages: 1160-1165
BACKGROUND: The literature on laparoscopic restorative proctectomy (RP) and proctocolectomy (RPC) is limited. This study compared clinical outcomes of laparoscopic RP and RPC with those of conventional open surgery at one centre. METHODS: Data were analysed from consecutive patients undergoing RPC and RP between November 2006 and November 2011. A standard laparoscopic technique was developed during the first 2 years, performed by two laparoscopic surgeons, with selection of patients who had not previously undergone open colectomy. Study endpoints included postoperative length of stay, 30-day morbidity, readmission, reoperation, pouch function and failure. RESULTS: A total of 207 patients were included; open surgery was performed in 131 (63·3 per cent) and a laparoscopic procedure in 76 (36·7 per cent). There were no significant differences in patient demographics. The conversion rate was 9 per cent (7 of 76). The median (i.q.r.) duration of operation was shorter for open than for laparoscopic procedures: 208 (178-255) versus 285 (255-325) min respectively (P < 0·001). Laparoscopic RPC had a shorter length of stay: median (i.q.r.) 6 (4-8) versus 8 (7-12) days (P < 0·001). The rate of minor complications was lower in the laparoscopic group (33 versus 50·4 per cent; odds ratio (OR) 0·48, 95 per cent confidence interval 0·27 to 0·87).There were no significant differences in total complications (51 per cent after laparoscopy versus 61·5 per cent after open surgery; OR 0·66, 0·37 to 1·17), anastomotic leakage, major morbidity, 30-day readmission, reoperation and stoma closure rates. Pouch failure (including permanent stoma) occurred in 14 (7·7 per cent) of 181 patients. Three patients died, all in the open surgery group. CONCLUSION: Laparoscopic RPC is feasible with some short-term advantages.
Lee G, Malietzis G, Bernardo D, et al., 2014, Activation and homing profile of dendritic cells in human colorectal cancer - effect of tumour derived factors or leaky lymph nodes?, EUROPEAN JOURNAL OF CANCER, Vol: 50, Pages: S217-S217, ISSN: 0959-8049
Lee G, Malietzis G, Bernardo D, et al., 2014, Circulating dendritic cells are gut homing in colorectal cancers - A role in diagnosis and prognosis in colorectal cancer?, EUROPEAN JOURNAL OF CANCER, Vol: 50, Pages: S217-S217, ISSN: 0959-8049
Lee G, Latchford A, Phillips R, et al., 2014, PTU-007 Development Of A Smartphone App To Aid The Clinical Management Of Polyposis Syndromes., Gut, Vol: 63 Suppl 1
Smartphone "apps" are becoming increasingly used by health care professionals (HCPs) as a quick and easy guide for delivering evidence-based medicine. "Apps" are particularly effective in providing guidelines accessible from a smartphone with contents that can be updated frequently. The Polyposis Registry at our institution has spearheaded the formulation of guidelines for the management of inherited polyposis syndromes. We set out to develop these into "app" form.
La Nauze R, Suzuki N, Saunders B, et al., 2014, The endoscopist's guide to serrated polyposis., Colorectal Dis, Vol: 16, Pages: 417-425
AIM: Serrated polyposis is a condition of the colon characterized by multiple serrated polyps. This review aims to provide a practical guide to the day-to-day management of serrated polyposis, including diagnosis, endoscopic identification of serrated polyps, surveillance, the role of endoscopic and surgical management and the screening of family members. METHOD: The literature was searched using PubMed and MEDLINE databases for the terms "serrated polyp", "serrated polyposis" and "hyperplastic polyposis". English-language abstracts were read and the full article was retrieved if relevant to the review. Expert opinion from the authors was also sought. RESULTS: Advances in our knowledge of the molecular pathways involved in serrated polyposis and an improved clinical picture of the disease from retrospective studies have led to better understanding of its pathogenesis and natural history. However, there are still areas not answered by the literature, and hence empirical management or expert opinion has to be followed. CONCLUSION: Improvements in our understanding of serrated polyposis, together with improvements in endoscopic equipment and technique, have enabled the endoscopist to be at the forefront of managing this condition from diagnosis to endoscopic surveillance and control of the polyps.
Rameshshanker R, Gupta A, O'Rourke A, et al., 2014, SHOULD MR ENTEROGRAPHY BE THE PREFERRED SURVEILLANCE MODALITY COMPARED TO SMALL BOWEL CAPSULE ENDOSCOPY IN PEUTZ-JEGHER'S SYNDROME?, GUT, Vol: 63, Pages: A55-A55, ISSN: 0017-5749
Monahan KJ, Clark SK, British Society of Gastroenterology BSG Cancer Group, 2014, A national survey of hereditary colorectal cancer services in the UK., Frontline Gastroenterol, Vol: 5, Pages: 130-134, ISSN: 2041-4137
OBJECTIVES: The British Society of Gastroenterology (BSG) Cancer Group designed a survey to determine how we might understand and improve the service for patients at elevated risk of hereditary colorectal cancer (CRC). DESIGN AND SETTING: United Kingdom (UK) gastroenterologists, colorectal surgeons, and oncologists were invited by email to complete a 10 point questionnaire. This was cascaded to 1,793 members of the Royal College of Radiologists (RCR), Association of Cancer Physicians (ACP), the Association of Coloproctology of Great Britain and Ireland (ACPGBI), as well as BSG members. RESULTS: Three hundred and eighty-two members responded to the survey, an overall response rate of 21.3%. Although 69% of respondents felt there was an adequate service for these higher risk patients, 64% believed that another clinician was undertaking this work. There was no apparent formal patient pathway in 52% of centres, and only 33% of centres maintain a registry of these patients. Tumour block testing for Lynch Syndrome is not usual practice. Many appeared to be unaware of the BSG/ACPGBI UK guidelines for the management of these patients. CONCLUSIONS: There is wide variability in local management and in subsequent clinical pathways for hereditary CRC patients. There is a perception that they are being managed by 'another', unspecified clinician. National guidelines are not adhered to. We therefore recommend improved education, well defined pathways and cyclical audit in order to improve care of patients with hereditary CRC risk.
Brigic A, Cahill RA, Bassett P, et al., 2014, A prospective case controlled study of the short-term outcome following hemicolectomy for benign compared with malignant colonic polyps, COLORECTAL DISEASE, Vol: 16, Pages: 179-185, ISSN: 1462-8910
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- Citations: 6
Lee GH, Askari A, Malietzis G, et al., 2014, The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review, CURRENT CANCER DRUG TARGETS, Vol: 14, Pages: 610-620, ISSN: 1568-0096
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- Citations: 17
Brigic A, Southgate A, Sibbons PD, et al., 2013, Full-thickness laparoendoscopic stapled excision of colonic lesion in a porcine ex vivo model, ENDOSCOPY, Vol: 45, Pages: E167-E168, ISSN: 0013-726X
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- Citations: 2
Brigic A, Southgate A, Sibbons P, et al., 2013, Full-thickness laparoendoscopic colonic excision in an experimental model, BRITISH JOURNAL OF SURGERY, Vol: 100, Pages: 1649-1654, ISSN: 0007-1323
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- Citations: 14
Mallappa S, Samarasinghe M, Gabe S, et al., 2013, Hyperaldosteronism and abnormal glucose tolerance following colectomy in patients with familial adenomatous polyposis (FAP) - A pilot study., Int J Surg, Vol: 11
Brigic A, Symons NRA, Faiz O, et al., 2013, A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 27, Pages: 3520-3529, ISSN: 0930-2794
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- Citations: 19
Lee G, Malietzis G, Yssin N, et al., 2013, Increased activation and migration potential of dendritic cell in patients with colorectal cancer - the implication and future of cancer immunotherapy, European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO, Publisher: ELSEVIER SCI LTD, Pages: S498-S499, ISSN: 0959-8049
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