Leadership training to improve adenoma detection rate in screening colonoscopy: A randomised trial

Objective Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared t

Evidence for substrate assisted catalysis in <i>N</i>-acetylphosphoglucosamine mutase

11 pags, 4 figs, 2 tabs . -- Supplementary data is available at the Publisher's web pageN-acetylphosphoglucosamine mutase (AGM1) is a key component of the hexosamine biosynthetic pathway that produces UDP-GlcNAc, an essential precursor for a wide range of glycans in eukaryotes. AGM belongs to the α-D-phosphohexomutase metalloenzyme superfamily and catalyzes the interconversion of N-acetylglucosamine-6-phosphate (GlcNAc-6P) to N-acetylglucosamine-1-phosphate (GlcNAc-1P) through N-acetylglucosa-mine-1,6-bisphosphate (GlcNAc-1,6-bisP) as the catalytic intermediate. Although there is an understanding of the phosphoserine-dependent catalytic mechanism at enzymatic and structural level, the identity of the requisite catalytic base in AGM1/phosphoglucomu-tases is as yet unknown. Here, we present crystal structures of a Michaelis complex of AGM1 with GlcNAc-6P and Mg, and a complex of the inactive Ser69Ala mutant together with glucose-1,6-bisphosphate (Glc-1,6-bisP) that represents key snapshots along the reaction co-ordinate. Together with mutagenesis, these structures reveal that the phosphate group of the hexose-1,6-bisP intermediate may act as the catalytic base.This work was funded by the MRC Programme Grant M004139

Endoscopic management of Lynch syndrome and of familial risk of colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Main Recommendations ESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures. Strong recommendation, low quality evidence, level of agreement 100 %. ESGE recommends starting colonoscopy surveillance at the age of 25 years for MLH1 and MSH2 mutation carriers and at the age of 35 years for MSH6 and PMS2 mutation carriers. Strong recommendation, moderate quality evidence, level of agreement 100 %. ESGE recommends the routine use of high-definition endoscopy systems in individuals with Lynch syndrome. Strong recommendation, high quality evidence, level of agreement 100 %. ESGE suggests the use of chromoendoscopy may be of benefit in individuals with Lynch syndrome undergoing colonoscopy; however routine use must be balanced against costs, training, and practical considerations. Weak recommendation, moderate quality evidence, level of agreement 89 %. ESGE recommends definition of familial risk of colorectal cancer as the presence of at least two first-degree relatives with colorectal cancer or at least one first-degree relative with colorectal cancer before the age of 50 years. Strong recommendation, moderate quality evidence, level of agreement 92 %. ESGE recommends colonoscopy surveillance in first-degree relatives of colorectal cancer patients in families that fulfill the definition of familial risk of colorectal cancer. Strong recommendation, moderate quality evidence, level of agreement 100 %.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Personalized endoscopic surveillance and intervention protocols for patients with familial adenomatous polyposis: the European FAP Consortium strategy

Background and study aims: Patients with familial adenomatous polyposis (FAP) undergo colectomy and lifelong endoscopic surveillance to prevent colorectal, duodenal and gastric cancer. Endoscopy has advanced significantly in recent years, including both detection technology as well as treatment options. For the lower gastrointestinal tract, current guidelines do not provide clear recommendations for surveillance intervals. Furthermore, the Spigelman staging system for duodenal polyposis has its limitations. We present a newly developed personalized endoscopic surveillance strategy for the lower and upper gastrointestinal tract, aiming to improve the care for patients with FAP. We aim to inform centers caring for FAP patients and encourage the discussion on optimizing endoscopic surveillance and treatment in this high-risk population. Methods: The European FAP Consortium, consisting of endoscopists with expertise in FAP, collaboratively developed new surveillance protocols. The proposed strategy was consensus-based and a result of several consortium meetings, discussing current evidence and limitations of existing systems. This strategy provides clear indications for endoscopic polypectomy in the rectum, pouch, duodenum and stomach and defines new criteria for surveillance intervals. This strategy will be evaluated in a 5-year prospective study in nine FAP expert centers in Europe. Results: We present a newly developed personalized endoscopic surveillance and endoscopic treatment strategy for patients with FAP aiming to prevent cancer, optimize endoscopic resources and limit the number of surgical interventions. Following this new strategy, prospectively collected data in a large cohort of patients will inform us on the efficacy and safety of the proposed approaches.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Przygotowanie jelita do kolonoskopii: Zalecenia Europejskiego Towarzystwa Endoskopii Przewodu Pokarmowego

 CEL: Niniejsze zalecania są oficjalnym stanowiskiem Europejskiego Towarzystwa Endoskopii Przewodu Pokarmowego (ESGE, European Society of Gastrointestinal Endoscopy) na temat wyboru sposobu przygotowania jelita do kolonoskopii.METODY: Zalecania opracowano na podstawie przeglądu literatury ukierunkowanego na dowody dotyczące przygotowania jelita do kolonoskopii. Siła zaleceń i jakość dowodów, na których je oparto zostały określone przy użyciu systemu GRADE (Grading of Recommendations Assessment, Development and Evaluation).WYNIKI: Najważniejsze zalecenia są następujące:1. ESGE zaleca w dniu poprzedzającym kolonoskopię dietę ubogoresztkową (słabe zalecenie, dowody umiarkowanej jakości);2. ESGE zaleca w rutynowym przygotowaniu do kolonoskopii 4 litry roztworu glikolu polietylenowego (PEG) w dwóch dawkach podzielonych lub, w przypadku kolonoskopii wykonywanej po południu, w jednorazowej dawce porannej. Alternatywą, szczególnie w przygotowaniu do kolonoskopii w warunkach ambulatoryjnych, może być podanie 2 l PEG z kwasem askorbinowym lub pikosiarczanu sodu z cytrynianem magnezu w dwóch dawkach podzielonych lub, w przypadku kolonoskopii wykonywanej po południu, w jednorazowej dawce porannej (silne zalecenie, dowody wysokiej jakości). Odstęp pomiędzy ostatnią dawką preparatu do przygotowania a kolonoskopią nie powinien przekraczać 4 godzin;3. ESGE radzi ze względów bezpieczeństwa nie używać rutynowo do przygotowania do kolonoskopii preparatów fosforanu sodu (silne zalecenie, dowody niskiej jakości).

Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years

Objective The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years. Design Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change. Results We retrieved data on 143.7million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively. Conclusion CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered

Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

ESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and endoscopic performance measures. Strong recommendation, moderate quality of evidence, level of agreement 90\u200a%.ESGE recommends performing esophagogastroduodenoscopy, small-bowel examination, and/or colonoscopy earlier than the planned surveillance procedure if a patient is symptomatic. Strong recommendation, low quality of evidence, level of agreement 100\u200a%

Contribuição de constituintes de solo à capacidade de troca de cátions obtida por diferentes métodos de extração Contribution of soil constituents to the cation exchange capacity as determined by different extraction methods

A capacidade de troca de cátions (CTC) é uma propriedade físico-química intrínseca aos constituintes minerais e orgânicos do solo. Apesar do uso de diferentes extratores e procedimentos, a CTC é normalmente expressa considerando apenas o controle ou não do pH na solução extratora. O objetivo deste trabalho foi discutir o significado da contribuição da matéria orgânica do solo prepresentada pelo carbono orgânico total (COT) e da argila à capacidade de troca de cátions de um Argissolo quando diferentes métodos estão envolvidos na determinação desse parâmetro. Para isso, utilizaram-se 75 amostras de um Argissolo Vermelho-Amarelo distrófico abrúptico da área do Departamento de Solos da Universidade Federal de Santa Maria, representando, em triplicata, cinco profundidades e cinco sistemas de uso e manejo de solo. A CTC efetiva (CTC E) foi estimada pelo cloreto de hexamina cobalto (CTC E Cohex) e pela soma de cátions Al3+, Ca2+, Mg2+ e K+ (CTC E SB + AlKCl), os três primeiros extraídos por KCl e o último por Mehlich-1; a CTC em pH 7,0 (CTC7) foi estimada por acetato de amônio (CTC7 Metson) e pela soma de cátions Ca2+, Mg2+ e K+ e H + Al estimado pelo índice SMP (CTC7 SB + H + AlSMP). Os valores de CTC obtidos pelos diferentes métodos se relacionam entre si, com coeficientes de correlação linear simples acima de 0,93. Os valores de CTC7 Metson são subestimados quando comparados com o método CTC7 (SB + H + AlSMP). Nesse sentido, as contribuições da argila e do COT à CTC7 foram, respectivamente, menores para a CTC7 Metson, 19 e 256 cmol c kg-1, que para a CTC7 (SB + H + AlSMP), 23 e 399 cmol c kg-1. A contribuição dos constituintes de solo depende, então, do cátion extrator e da capacidade de extração dos métodos empregados.<br>The cation exchange capacity (CEC) is a physicochemical property dependent on mineral and organic soil constituents. Despite the use of different procedures and extractors the CEC is normally expressed considering only the pH control or not of the extracted solution. This study aims to discuss the significance of the contribution of organic carbon and clay to the CEC of an Acrisol, using different determination methods. For this purpose, 75 samples of an abruptic Red-Yellow Acrisol from the Universidade Federal de Santa Maria campus were used, representing five layers and five land use and management systems, in triplicate. The CEC E was estimated by cobalt hexamine trichloride (CEC E Cohex) and by the sum of cations Al3+ , Ca2+, Mg2+, and K+ (CEC E SB+AlKCl), the first three extracted by KCl and the last by Mehlich-1; the CEC7 was estimated by ammonium acetate (CEC7 Metson) and the sum of bases Ca2+ , Mg2+and K+ and H+Al was estimated by the SMP index (CEC7 SB+H+AlSMP). The CEC values obtained with the different methods are correlated, with coefficients of determination over 0.93. The CEC7 Metson values are subestimated when compared with those by CEC7 (SB+H+AlSMP). The contribution of clay and organic carbon to CEC7 was, respectively, 23 and 399 cmol c kg-1 for CEC7 (SB+H+AlSMP) and 19 and 256 cmol c kg-1 for CEC7 Metson. The contribution of the soil constituents depends on the extracting cation and the performance of the extraction methods employed

Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2019

1:  ESGE suggests that high definition endoscopy, and dye or virtual chromoendoscopy, as well as add-on devices, can be used in average risk patients to increase the endoscopist's adenoma detection rate. However, their routine use must be balanced against costs and practical considerations.Weak recommendation, high quality evidence. 2:  ESGE recommends the routine use of high definition systems in individuals with Lynch syndrome.Strong recommendation, high quality evidence. 3:  ESGE recommends the routine use, with targeted biopsies, of dye-based pancolonic chromoendoscopy or virtual chromoendoscopy for neoplasia surveillance in patients with long-standing colitis.Strong recommendation, moderate quality evidence. 4:  ESGE suggests that virtual chromoendoscopy and dye-based chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps and can replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained, as defined in the ESGE curriculum, and audited.Weak recommendation, high quality evidence. 5:  ESGE recommends the use of high definition white-light endoscopy in combination with (virtual) chromoendoscopy to predict the presence and depth of any submucosal invasion in nonpedunculated colorectal polyps prior to any treatment. Strong recommendation, moderate quality evidence. 6:  ESGE recommends the use of virtual or dye-based chromoendoscopy in addition to white-light endoscopy for the detection of residual neoplasia at a piecemeal polypectomy scar site. Strong recommendation, moderate quality evidence. 7:  ESGE suggests the possible incorporation of computer-aided diagnosis (detection and characterization of lesions) to colonoscopy, if acceptable and reproducible accuracy for colorectal neoplasia is demonstrated in high quality multicenter in vivo clinical studies. Possible significant risks with implementation, specifically endoscopist deskilling and over-reliance on artificial intelligence, unrepresentative training datasets, and hacking, need to be considered. Weak recommendation, low quality evidence