St Mark's Hospital

Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.

Over the last 10-15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.

Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes after receiving a single intravenous dose of the drug, all six volunteers had a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after infusion, they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation. Severe and unexpected depletion of lymphocytes and monocytes occurred within 24 hours after infusion. All six patients were transferred to the care of the authors at an intensive care unit at a public hospital, where they received intensive cardiopulmonary support (including dialysis), high-dose methylprednisolone, and an anti-interleukin-2 receptor antagonist antibody. Prolonged cardiovascular shock and acute respiratory distress syndrome developed in two patients, who required intensive organ support for 8 and 16 days. Despite evidence of the multiple cytokine-release syndrome, all six patients survived. Documentation of the clinical course occurring over the 30 days after infusion offers insight into the systemic inflammatory response syndrome in the absence of contaminating pathogens, endotoxin, or underlying disease.

Infection, ischaemia, physical damage, or specific immunologic sensitivity should be excluded as far as possible before a diagnosis of non-specific inflammatory bowel disease is made. Non-specific inflammations can be subdivided on the basis of macroscopic and microscopic anatomical criteria. Macroscopic structural abnormalities can be recognized by clinical examination, endoscopy, radiology, and inspection of an operation specimen. These complementary methods of data collection combine with microscopic examinations of tissue to separate disorders that differ in prognosis and possible response to treatment. Anatomic classifications do not necessarily imply differences in aetiology and may change with advances in knowledge.

This is the third European Crohn’s and Colitis Organisation [ECCO] consensus guideline that addresses ulcerative colitis [UC]. It has been drafted by 28 ECCO members from 14 European countries. It is derived from and updates the previous ECCO consensus advice on UC.1–3 All the authors recognise and are grateful to previous ECCO members who contributed to creating the previous consensus guidelines1–6 on which some of the text is based. Attention is also drawn to other ECCO consensus guidelines which have contributed to this endeavour, on extra-intestinal manifestations [EIMs],7 malignancy,8 imaging,9 small bowel endoscopy,10 opportunistic infections [OIs],11 surgery,12 endoscopy,13 pathology,14 anaemia,15 reproduction and pregnancy,16 and paediatric UC.17 The guideline has been condensed into two papers, the first detailing definitions, classification, diagnosis, imaging, pathology, and management of special situations [EIMs, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders of UC]; and the second describing current therapeutic management [treatment of active disease and maintenance of medically induced remission]. The strategy to define consensus was similar to that previously described in other ECCO consensus guidelines [available at www.ecco-ibd.eu]. Briefly, an open call for participants was made, with participants selected by the Guidelines’ Committee of ECCO [known as GuiCom] on the basis of their publication record and a personal statement. Working parties were established to review the consensus statements published in 2012,1–3 after which a recommendation was issued on whether they required revision based upon advances in the published literature. There was agreement that extensive review of histopathology, endoscopy, OI, anaemia, EIMs, surgery, and pregnancy was not required, as these subjects are reviewed in other recent ECCO guidelines7,11–16; rather, abbreviated text and selected statements from these guidelines specific to UC are provided. Paediatric UC is dealt with in a separate ECCO initiative17 which is currently being updated. Provisional ECCO statements and supporting text were written following a comprehensive literature review, then refined following two voting rounds which included national representative participation by ECCO’s 35 member countries. The level of evidence was graded according to the Oxford Centre for Evidence-Based Medicine [www.cebm.net]. The ECCO statements were finalised by the authors at a meeting in Barcelona in October 2015 and represent consensus with agreement of at least 80% of participants. Consensus statements are intended to be read in context with their qualifying comments and not in isolation. The supporting text was then finalised under the direction of each working group leader [FM, FC, AD, PG, FR], including an updated literature search to October 2016 of the most relevant [eight] journals, before being integrated by a consensus leader [MH]. This consensus guideline is pictorially represented within the freely available ECCO e-Guide [http://www.e-guide.ecco-ibd.eu/]. UC is a lifelong disease arising from an interaction between genetic and environmental factors, observed predominantly in developed countries. Its precise aetiology is unknown, and therefore curative medical therapy is not yet available. Within Europe there is an east-west and north-south gradient, but the incidence appears to have increased in southern and eastern countries during recent years.18–20 Patients may live with a considerable symptom burden and high risk of disability21 despite medical treatment.22 Clinicians must advise and treat patients on the basis of currently available information. Despite robust evidence from rigorously conducted randomised trials, the strict and somewhat necessarily restrictive inclusion and exclusion criteria in trial design may limit translation of such evidence to ‘real-world’ patients. Ulcerative colitis [UC] is a chronic inflammatory condition that causes continuous mucosal inflammation of the colon, usually without granulomas on biopsy. It affects the rectum and to a variable extent the colon in a continuous fashion, and is characterised by a relapsing and remitting course.23 Inflammatory bowel disease unclassified [IBDU] is the term best suited for a minority of cases in which a definitive distinction between UC, Crohn’s disease, or other causes of colitis cannot be made after taking into account the history, endoscopic appearance, histopathology of multiple mucosal biopsies, and appropriate radiology.23,24 Indeterminate colitis is a term reserved for pathologists to describe a colectomy specimen with overlapping features of UC and Crohn’s disease.24,25 Detailed information on definitions can be found in Supplementary material, available as Supplementary data at ECCO-JCC online.1,23,24,26–39 Distribution of UC [adapted from Silverberg et al.23]. Disease activity in UC [adapted from Truelove & Witts32]. Montréal classification of disease activity in UC [adapted from Silverberg et and et Disease extent whether therapy and and of It is by the extent at as and extensive colitis of inflammation the management and the of for a therapy in the of or is usually the for and therapy with is appropriate for extensive of colitis the risk of of or cancer and the and the of Patients with extensive colitis have the risk of with have a risk similar to the Patients with colitis an their risk that of patients with extensive colitis as disease patients with and extensive colitis are to have patients with not such It be that the extent at may the extent of disease as with and are to the extent of information and risk for of or colitis may in of patients with Disease and of of disease have not been imaging, and endoscopic including histopathology, on management is as and at of a inflammatory of disease It be to the of active colitis by and before which may causes of that active disease such as mucosal Crohn’s disease, or bowel and patients with active disease including to Patients with an appropriate also have to a from of patients are in at during a a of a relapsing after of Disease activity in the first after to an increased of of active a an was between the to first and the of a the the was patients a for the maintenance of in patients with at patients from to at and from to at in the of described the in patients in the first following of UC between and the most recent the of patients an during the first after was a or within the first but and an activity at least during the first is also UC, a chronic inflammatory was in and were in of patients with an inflammatory after of with who without such an were in with and mucosal The of bowel inflammation is also a risk for in patients with extensive Detailed information on the of can be found in Supplementary material, available as Supplementary data at ECCO-JCC and and are of have been with of The is not as in UC as is in Crohn’s disease for the of disease in colitis have been established for and patients a to following for colitis with to a is for and have been but has been to be to The most are and other such as and have also at has for and of disease a with endoscopic and to can be as a for in patients with inflammatory bowel disease of was with an increased risk of It must be that of these is specific for UC, they represent active with disease there is of The consensus group that the best to define is a of with and mucosal at classification of ulcerative colitis according to at is of as disease has a according to the of is as the for and of patients with UC to have disease and and with All current available for UC have an in with The risk of in patients with UC the of is an in patients with UC, as the risk for The of genetic or is not for the classification of ulcerative colitis Detailed information on can be found in Supplementary material, available as Supplementary data at ECCO-JCC of ulcerative colitis are upon extent and of disease and and and are bowel and colitis UC in and the may be made at small in incidence has been in some after the of UC appears to The inflammation in the rectum and in a and to a variable extent of the colon, or mucosal The extent of inflammation may or but after disease the of inflammation to the extent of previous in the of The that UC continuous inflammation been by of a in and of patients with active UC the of mucosal disease, and may according to disease in for extensive UC from most cases of Patients with active disease also of and patients with usually with and may in UC, or the of Crohn’s The of UC is usually are for or before medical advice is with a in with including and EIMs, in or and may the in of cases and can in of of ulcerative colitis or Crohn’s disease the risk for ulcerative colitis for before and the risk and of UC may to ulcerative colitis of patients with UC have an increased risk of the The risk of UC is in but is also in and of UC as as in of patients with Crohn’s disease in a and the of but may not the of the have a risk of the disease, which is extensive and to with who have or but the data are and during or are to a risk of UC in The of is to that of but not to the of is after the of UC, the on the of disease is and is to may the evidence from and a trial that with is medical the of and and extra-intestinal with and of inflammatory bowel disease or and previous be The of UC is in the context of or of colitis be and be and and for and and may be may be in patients with or disease on on the extent and of of patients with or activity is usually from on Patients with a may and bowel for of ulcerative colitis not It is established by imaging, and endoscopic including be with review after an may be The of UC is characterised by of and of continuous in of the as a by The that of patients a in The of of is usually during the first and may be characterised as continuous UC without or the recent the of patients with UC in from at the of to after of It is to the diagnosis, and of disease, as these and disease It is to the to to a diagnosis, but mucosal active UC as the of of the may to Crohn’s disease or be during the first and and The be including be and be diagnosis, have a inflammatory and and a for is an of of chronic inflammation may be in or The may as a of the chronic inflammatory or chronic active disease, and which the of an UC, and with the of with patients with an is with an and have been as to the for colectomy in after a of extensive colitis an increased risk of is specific to UC from or other causes of be to and for may be according to the medical history, for the of for or other or with are required at and may be required to disease is in patients with colitis This for and is a and has been with and ECCO guidelines with disease be in the of or of can in UC, not in patients with may not disease can or It be in patients who The for relevant in patients with colitis has not been but most of in the inclusion with on histopathology not necessarily but multiple are usually including information on can be reviewed in the ECCO Consensus on and in a recent The most are and are in to of patients with UC and in of patients with Crohn’s the current of these their for the of UC and for therapeutic is not such as and have been as of inflammation in appears to be the most the of in patients for in the of disease with endoscopic and in the of and to with the to between of a in the of UC a to inflammation and to be a to a of patients by and has been described in with a or inflammation in the rectum is to to inflammation in the is to as a and may be observed in patients with the of and or a in of the small bowel in to an is The of patients with inflammation to be similar to with of the as a is in to of patients with inflammation has been with a and a risk of after pouch a recent a similar in patients with an of inflammation with with a in of disease and of or inflammation from the into is and is observed in to of patients with extensive may in patients without which the that that from a of into the Patients with to be to a of which may an increased risk of colon in not to be with pouch of the small bowel be in cases of to UC from Crohn’s bowel by or or endoscopy, as reviewed in the ECCO consensus on in Crohn’s and small bowel in is not is the of an to Crohn’s disease in to an is for endoscopic disease activity in ulcerative colitis are available. The of a endoscopic is to of ulcerative colitis patients and to a for inflammatory bowel disease to is for patients criteria for to which may to increased and The classification of UC was by Truelove and in This classification is to be the for of in of to and the of patients with colitis have inflammatory or and with a for and of be to and to the extent of disease and for features that to The extent of disease with the of in a of the extent of disease was in and in The of mucosal by or two of small bowel is with a to the of colitis and may be required is as a on with high in which histopathology be with a within before is in patients with colitis is not in in patients on criteria for colitis with mucosal on the of these and of which can be by is of is appropriate at for or ulcerative colitis or colectomy Despite the of disease in risk of and of the of after has been a mucosal after of was with a risk of in of the patients with mucosal with of without of patients who endoscopic as a of inflammation at and on during of in to of patients that to endoscopic in patients with UC, who were the disease and endoscopic after and and then at the third were to patients with or between and in the of and colectomy were of mucosal was the with and a disease patients with UC with and in that with endoscopic as with to after patients in The most endoscopic of ulcerative colitis is with of inflammation and ulcerative colitis is by mucosal and at the and in a and The between and is usually and may within in in the endoscopic of disease activity is and have been to the of endoscopic and are within the for UC, which is for trial The Ulcerative Colitis of the and the of and each with or of This is the first endoscopic of in The is the of in the of the colon at the of the a of to the of a a was made to the of the a to a of that the of the from to for ulcerative for The endoscopic features of inflammation are and at least of the active colitis is characterised by a of to the of the and 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to and may be in and with There and updates of the ECCO guideline on and is in UC, found in of for of et criteria for on the level of patients without or evidence of active disease, is an appropriate the of a to may be with the of or evidence of the criteria for of chronic disease are and the level is between and a of and of chronic disease is The most of in UC are of chronic disease, and a of or anaemia, and are but also be is by the as a in to a of in and in All UC patients be for anaemia, and this a and be with and is with and The level of with and is by the of and in et is in ulcerative colitis patients is Detailed information on and can be found in Supplementary material, available as Supplementary data at ECCO-JCC is the second most in UC, in of can be as and of with ulcerative colitis is based on of inflammation and exclusion of other specific of classification for has been but not is and affects in an This is and and is with disease is a and which affects small is of UC and can 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under for can be or UC patients are not but may have as a of their medical in et is an risk for and in the risk of in a of for All for the of OI, and the of at a may an increased risk of This risk is of the and of but may be by the of OI, have not been to the risk of All ulcerative colitis patients be for at patients with also be is in patients with ulcerative colitis of is in inflammatory bowel disease, by the disease and by the be after of the may be required to of be in patients at risk and for at least after has patients who are with high to of the of in to of with therapy in ulcerative colitis be but therapy is not is the increased risk of UC patients be to is not a for in et UC patients also be for the be by not a with or is but they can the of in on or can be found in Supplementary material, available as Supplementary data at ECCO-JCC information on and can be found in Supplementary material, available as Supplementary data at ECCO-JCC of in patients with is increased and is in 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for cancer The most risk for are an increased risk of to and disease may be of previous inflammatory and have also been found to be a risk of is with an increased the risk

BACKGROUND: Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. METHODS: In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study--PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle)--samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study--GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study)--samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. RESULTS: In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). CONCLUSIONS: Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.).

BACKGROUND: Lacerations of the anal sphincter or injury to sphincter innervation during childbirth are major causes of fecal incontinence, but the incidence and importance of occult sphincter damage during routine vaginal delivery are unknown. We sought to determine the incidence of damage to the anal sphincter and the relation of injury to symptoms, anorectal physiologic function, and the mode of delivery. METHODS: We studied 202 consecutive women six weeks before delivery, 150 of them six weeks after delivery, and 32 with abnormal findings six months after delivery. Symptoms of anal incontinence and fecal urgency were assessed, and anal endosonography, manometry, perineometry, and measurement of the terminal motor latency of the pudendal nerves were performed. RESULTS: Ten of the 79 primiparous women (13 percent) and 11 of the 48 multiparous women (23 percent) who delivered vaginally had anal incontinence or fecal urgency when studied six weeks after delivery. Twenty-eight of the 79 primiparous women (35 percent) had a sphincter defect on endosonography at six weeks; the defect persisted in all 22 women studied at six months. Of the 48 multiparous women, 19 (40 percent) had a sphincter defect before delivery and 21 (44 percent) afterward. None of the 23 women who underwent cesarean section had a new sphincter defect after delivery. Eight of the 10 women who underwent forceps delivery had sphincter defects, but none of the 5 women who underwent vacuum extractions had such defects. Internal-sphincter defects were associated with a significantly lower mean (+/- SD) resting anal pressure (61 +/- 11 vs. 48 +/- 10 mm Hg, P < 0.001) six weeks post partum, and external-sphincter defects were associated with a significantly lower squeeze pressure (increase above resting pressure, 70 +/- 38 vs. 44 +/- 13 mm Hg; P < 0.001). There was a strong association (P < 0.001) between sphincter defects and the development of bowel symptoms. CONCLUSIONS: Occult sphincter defects are common after vaginal delivery, especially forceps delivery, and are often associated with disturbance of bowel function.

BACKGROUND: Existing scales for assessing faecal incontinence have not been validated against clinical assessment, or with regard to reproducibility. They also fail to take into account faecal urgency, and the use of antidiarrhoeal medications. AIMS: To establish the validity, and sensitivity to change, of existing scales and a newly designed incontinence scale. METHODS: (1) Twenty three patients (21 females, median age 57 years) were prospectively evaluated by two independent clinical observers, using three established scales (Pescatori, Wexner, American Medical Systems), a newly devised scale which also includes details about urgency and antidiarrhoeal drugs, and by a 28 day diary. (2) A further 10 female patients were assessed by the same scales before and after surgery for faecal incontinence. RESULTS: (1) Assessments by two independent clinicians correlated well. All four scales and a diary card correlated highly and significantly with the clinical impression, with the new scale reaching the highest correlation (r=0.79, p<0.001). (2) All except one score changed significantly in response to surgical treatment; the new scale showed the greatest change, at the highest level of significance (p=0.004), and correlated best with the clinicians' assessment of change (r=0.94, p<0.001). CONCLUSIONS: Existing scales for the assessment of faecal incontinence correlate well with careful clinical impression of severity, and serve as useful and reproducible measures for comparison of patients and treatments. A newly devised scale has shown high clinical validity and utility.

Crohn’s disease [CD] is a chronic inflammatory bowel disease [IBD] that can result in progressive bowel damage and disability.1 CD can affect individuals of any age, from children to the elderly,2,3 and may cause significant morbidity and impact on quality of life. Up to one-third of patients present with complicated behaviour [strictures, fistula, or abscesses] at diagnosis.4 Most patients over time will develop a complication, with roughly 50% of patients requiring surgery within 10 years of diagnosis.5–7 As the precise aetiology of CD remains unknown, a curative therapy is not yet available.8 Several agents are available for the medical treatment of CD. Medical agents include mesalazine [5-ASA], locally active steroids [such as budesonide], systemic steroids, thiopurines such as azathioprine [AZA] and mercaptopurine [MP], methotrexate [MTX], and biologic therapies (such as anti-tumour necrosis factor [TNF], anti-integrins, and anti-interleukin [IL] 12/23]. The European Crohn’s and Colitis Organisation [ECCO] produces and regularly updates several guidelines aimed at providing evidence-based guidance on critical aspects of IBD care to all health care professionals who manage patients with IBD. To provide high-quality evidence-based recommendations on medical treatment in CD, ECCO decided to develop these guidelines by adopting the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] approach.9 GRADE is a systematic process for developing guidelines which addresses how to frame the health care questions, summarise the evidence, formulate the recommendations, and grade their strength and the quality of the associated evidence. GRADE increases transparency at all levels of this process and makes explicit the three considerations that lead to a particular recommendation: the quality of the evidence, the balance of benefits and harms, and the patients’ values and preferences. Therefore ECCO reviewed the available high-quality evidence on the medical management of CD and developed evidence-based recommendations on the medical treatment of adult patients with CD. These guidelines do not cover specific situations, such as postoperative management of adult patients with CD, which was already covered in the latest ECCO Guidelines on Crohn’s disease.10 Based on the GRADE workflow, the Guidelines Committee of ECCO [GuiCom] selected a panel of 48 experts supported by a team of methodologists and librarians. Selection was based on IBD expertise, scientific background, and knowledge of the GRADE methodology. All panellists received adequate training in GRADE before starting the process. Additionally, four patients with CD representing the European Federation of Crohn’s and Colitis Associations [EFCCA] were invited to participate in all face-to-face meetings and to provide their experiences and state their preferences. Three domains for medical treatment of CD were identified: 1] induction therapy; 2] maintenance therapy; 3] therapy of fistulising perianal disease. All panellists were assigned to one of three working groups coordinated by one to two working group leaders under the supervision of two Guideline coordinators. The panellists first formulated a series of specific questions using the PICO format [Population, Intervention, Comparator, Outcomes] which were deemed to be clinically important for the medical treatment of CD. The outcomes of all PICO questions were subsequently graded as ‘not important’, ‘important’, or ‘critical’ during a face-to-face kick-off meeting in Vienna, using a Delphi consensus process. A team of professional librarians performed a comprehensive literature search on EMBASE, PubMed/Medline, and Cochrane Central databases using specific search strings for each PICO question [Supplementary Files 1, 2, and 3, available as Supplementary data at ECCO-JCC online]. Two independent working group members [one assigned to the PICO and another one from the same group as a second reviewer] assessed the relevance of each abstract to PICO and included or excluded all the relevant papers for the final data extraction and analysis. Subsequently, the working group members assigned to each PICO question systematically reviewed and summarised the evidence on every outcome, to compile a Summary of Findings [SoF] table for each question. The GRADE method follows a hierarchical approach to synthesise evidence; recent high-quality systematic reviews and meta-analyses of clinical trials were preferentially used to create the recommendations. When these were not available, individual randomised clinical trials [RCTs] followed by observational studies were reviewed; results of individual studies were pooled using random-effects meta-analysis as appropriate and when needed. To define disease activity and severity [mild-to-moderate and moderate-to-severe], we accepted the definitions used by the investigators of the studies selected as an evidence basis for our work. The quality of evidence was classified into the following four categories in accordance with the GRADE approach: ‘high’ [meaning that further research is unlikely to change our in the research may change our in the research to change our in the and [meaning that any of is each PICO the quality of evidence was to the quality of evidence outcomes graded as The strength of each was graded as [meaning the of an the or or as [meaning the balance is the quality of evidence, values or and the outcomes were not in the clinical this was in the To the recommendations, we from the systematic reviews or our group of methodologists performed the All recommendations were to by the panel the ECCO for each with and from a of ECCO members who to the were not selected to be of the The final of all was panel members during a final consensus meeting in and to a final recommendations were at of the panellists with the and associated strength The of the and and the of the were reviewed by two Guideline Committee members and by the ECCO who the final of these The literature search the relevant definitions of and a of the and the the evidence can be in the Supplementary available as Supplementary data at ECCO-JCC As CD is a therapy to in the and in the The that chronic and results in to a recent in medical treatment and disease is that and may patients to their and therapy are to high-quality evidence is not available to this affect the of medical These include disease disease activity and to and of perianal or fistulising the individual for and the individual and the and of each be As is a clinical and is of to disease and therapy at based on and approach will provide the with the to therapy the of of the disease and which is to be to disease to the management of CD a series of health care maintenance be to be and be and appropriate guidance or for and be as in ECCO or the of for induction of of Crohn’s disease performed a meta-analysis of that the of or with in patients with active CD [Supplementary 1, available as Supplementary data at ECCO-JCC online]. The of from to patients with disease with or disease were was significant for induction of clinical [Supplementary 1, available as Supplementary data at ECCO-JCC online]. A recent Cochrane significant and to be in our as was significant in to when with [Supplementary 2, available as Supplementary data at ECCO-JCC online]. the trials of was over for clinical [Supplementary 3, available as Supplementary data at ECCO-JCC online]. significant in to was in trials that [Supplementary available as Supplementary data at ECCO-JCC online]. meta-analysis a significant on clinical the that at of another meta-analysis was to any such A pooled of three trials of a of a in the Crohn’s with the in and was not clinically Two trials with for induction of clinical A pooled a of [Supplementary available as Supplementary data at ECCO-JCC online]. was not by any significant in for [Supplementary available as Supplementary data at ECCO-JCC online]. in trials that the of was to patients with The of or for the treatment of CD not in using for the induction of clinical in patients with active Crohn’s disease to the A Cochrane systematic and included three that at a of with [Supplementary 2, available as Supplementary data at ECCO-JCC online]. Two of these clinical as in or at at was in all three was to for clinical and clinical in patients with active CD in the to the As with steroids which are associated with systemic activity and systemic and and a was to be in the reviewed A Cochrane systematic and meta-analysis from reviewed two that at a of with mesalazine to a mesalazine in patients with active CD [Supplementary 3, available as Supplementary data at ECCO-JCC online]. All trials clinical in or and clinical at was not to mesalazine for clinical in patients with active CD in the [Supplementary available as Supplementary data at ECCO-JCC online]. clinical was in patients in patients mesalazine [Supplementary available as Supplementary data at ECCO-JCC online]. The of was with and in groups [Supplementary and available as Supplementary data at ECCO-JCC online]. studies the of treatment on CD. and to clinical or with the of these the European on the of to or Therefore a was not on to CD, for the treatment of patients with Crohn’s we the of systemic for the induction of clinical and Two on the of systemic or with for the treatment of active available as Supplementary data at ECCO-JCC online]. was at a of 48 and on a basis to and of from to with a of is at over an from these studies in a Cochrane systematic patients on induction of clinical was in patients as with were to be as in clinical in the two studies patients on the of patients from the of systemic was available from one patients with The of was in patients with included of and in patients with and in was for the outcomes to which a quality of evidence the of thiopurines as for the induction of of Crohn’s disease Several studies on the of thiopurines with for induction of and in [Supplementary available as Supplementary data at ECCO-JCC online]. trials the of thiopurines for induction of clinical in with or patients were The active was in four of these and the active was in the The trials were in of of active and of for of the trials for the of The pooled was performed on an basis and for induction of thiopurines and in the active with in the group Three trials on clinical not with of disease these of of disease were of the patients as with of clinical The of clinical was was and to data and the quality of evidence was for this [Supplementary available as Supplementary data at ECCO-JCC online]. one on during The pooled of any was not and thiopurines were in two of of developed The quality of evidence was deemed to a of and on a quality of The groups was at for and for of the trials on at the of the induction data were available that for a pooled trials in of such as or in thiopurines as with a of at and at and for the thiopurines and a of in the group and a significant in in and one relevant was this patients with active CD were randomised to of or for with a of at that was over a [Supplementary available as Supplementary data at ECCO-JCC online]. a of patients with were in clinical The of treatment for and was in with this is by and such as the of studies were that for the induction of of CD. was in the the of for CD and the decided to Three and studies the of and thiopurines for induction of in [Supplementary available as Supplementary data at ECCO-JCC online]. These studies used and of Two studies used at of and and one used at All patients were and received systemic steroids at of the individual studies or the pooled a significant in the to [Supplementary available as Supplementary data at ECCO-JCC online]. the of is with the data are and the quality of evidence is for can be Based on the evidence, on a for the of for clinical in patients with CD not be may be as an for patients with disease when be The to therapy in patients a be the of and to in patients with Crohn’s disease who not to therapy are and therapies for the treatment of CD include and is not in the European for CD, is available in and is a at a of at 2, and during induction and every is a at a of and followed by every is a at a of at 2, and followed by every on agents and from several meta-analyses of their for induction of clinical and clinical [Supplementary available as Supplementary data at ECCO-JCC in patients who not adequate or were to data were available for the induction two studies a the evidence was to on clinical were and data on were by to the of patients included in the meta-analysis on outcomes and and and quality of are was in of The of on and in a that with and were to for induction of The of of biologic agents is a of that patients with fistulising perianal complicated from the of to a of or of agents be the first in disease these results are based on from clinical the of and thiopurines over to clinical and one the of therapy of with as with for the induction of clinical in patients to therapies [Supplementary available as Supplementary data at ECCO-JCC online]. this therapy was not to for clinical therapy was associated with at this was at the of was in to associated with therapy the of used in this was the used in CD patients of therapy with a when starting to in patients with Crohn’s who an to therapy The and Crohn’s the of with over in patients to who to to steroids or [Supplementary available as Supplementary data at ECCO-JCC online]. therapy in of clinical at as with therapy was to result in at this was in for were of in therapy A in clinical is patients who or an to thiopurines and in therapy is in such maintenance in with the benefits in of A of of the of therapy starting therapy in this be in the of evidence, an approach be for induction of in patients with Crohn’s disease with to therapy to therapy high-quality is an that to the by the and CD, induction be using a of systematic and meta-analysis pooled the results from in which was with for induction of in patients with active available as Supplementary data at ECCO-JCC online]. patients with or induction of clinical and induction of clinical at were and a meta-analysis was an of clinical of [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence was The of clinical was [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence was CD patients that of patients at as with of The quality of evidence was on or The pooled of any was not and [Supplementary available as Supplementary data at ECCO-JCC online]. the pooled of any was not and [Supplementary available as Supplementary data at ECCO-JCC the quality of evidence was The of to be for induction of and in patients with Crohn’s disease with to therapy to therapy is a that by the in is at a of at 2, and for and every who do not at can from an at Three randomised trials patients with or on induction of clinical induction of clinical and in adult patients with active available as Supplementary data at ECCO-JCC online]. in these studies were followed for to 10 was in patients with [Supplementary available as Supplementary data at ECCO-JCC online]. clinical was in patients with [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence for these outcomes was of with were not with [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence for this was to from the of or for the treatment of active Crohn’s disease in patients who therapy systematic and meta-analysis performed an of and for induction of in patients with active CD who were or to a of patients with or on induction of clinical and clinical [Supplementary available as Supplementary data at ECCO-JCC online]. The pooled of clinical and clinical were not and the quality of evidence was for a of patients with or on or The pooled of any was not and the pooled of any was not and the quality of evidence was surgery be as an in is for the induction of in patients with CD, as a and of at or a or a Crohn’s of with and is a knowledge on how to CD in of the the and or in patients with disease. Therefore the is to the who the individual and of systemic steroids are in in CD, are by important Additionally, of not disease Therefore we that the of or to steroids the of 10 or within of starting steroids, a within of steroids, or the for a of in all a are not in thiopurines a of and are for in CD patients are with steroids at the of patients with a of steroids and in at and is associated with a of this may be medical and surgery are not or are associated with individual patients with CD as a or with or to therapy we the of These include agents [such as and or All these agents are in and CD The on and and the induction of in the of with thiopurines is for of therapy over was in the performed to The the of or the of and over or in with this be and in The for the of Crohn’s that the of with in patients at of as with a was associated with of and for surgery in patients with A that is associated with to clinical the and of therapy to be a in in the therapy not to be associated with at in the a that therapy is associated with for and as with Therefore the is to the who and to be as specific such as the at for or and at for specific such as patients who or are is evidence on the and in patients with or as a first assessed the and of these agents when used in therapy as with to be in the in was in patients with in patients with CD with disease or to at one surgery be as an the of a for induction of and for using of clinical the or of therapy not on on the disease severity impact of disease in the individual the and for the inflammatory of and disease appropriate studies that the of over a on the of and and that for disease be studies were by this as important research the of for maintenance of in patients with Crohn’s disease for the maintenance of of CD [Supplementary available as Supplementary data at ECCO-JCC online]. significant [Supplementary available as Supplementary data at ECCO-JCC online]. trials that assessed and were from to with trials a of were significant in the of patients an or to or The data were and this [Supplementary available as Supplementary data at ECCO-JCC online]. are for the maintenance of in patients with Crohn’s disease The of maintenance treatment with or to patients with CD who are in one [Supplementary available as Supplementary data at ECCO-JCC online]. meta-analysis included data from trials and A of patients with to were included and followed for to was to in disease activity in was to for the maintenance of in patients outcomes were in four trials and a of patients followed for to The of during maintenance treatment with thiopurines was with The of in patients with thiopurines was and were the the of therapy in patients with Crohn’s disease for that the of thiopurines disease Two studies the of of the for of Crohn’s disease in and the trials [Supplementary available as Supplementary data at ECCO-JCC online]. The excluded from our table was not or the adult patients with a recent of CD were randomised to or to were to active disease in this The results were not significant for any of the critical outcomes of clinical not the two groups patients with and were in The of as and were in patients in the group and in the group methotrexate for the maintenance of in patients with Crohn’s disease on the of are from one patients were of or of for [Supplementary available as Supplementary data at ECCO-JCC online]. with active CD, who to of treatment with were assigned to at a of or for for CD were the of patients who in was in the group in the group 50% of the patients in the group by the of the were in in the group as with the group over the observational [one and the a and patients in the group in the of the was one treatment of these of severity to treatment or from the The of was in patients with Crohn’s disease who with maintenance treatment using the same treatment is Two systematic reviews the of maintenance treatment with and to patients with CD who disease with the same [Supplementary available as Supplementary data at ECCO-JCC online]. trials and were pooled in the meta-analysis from one was on two on and two on A of patients were included and followed for to of the studies included and one included all was as a The of with was The following values were with with and with A significant the three are pooled data available on of all as a performed in the of a Cochrane the for for and were and with is as with for the maintenance of in CD the and of do not the of that may in and observational for clinical in patients with Crohn’s disease who with at every was to in clinical in patients with CD who with [Supplementary available as Supplementary data at ECCO-JCC online]. patients every and patients every were in clinical as with patients and was at clinical and a of with data are to the the of to clinical in patients with Crohn’s disease who with outcomes for the maintenance of with in CD patients [Supplementary available as Supplementary data at ECCO-JCC to in the induction were to every or or a of the patients were in clinical as with of A that at clinical was by of patients every and by of patients every as with in the The treatment every and was and was treatment every and Therefore was every or was in of patients of patients The pooled of any was not patients who were and are data on as this was assessed in a of patients at was significant in patients in the group as with patients in the treatment were during the of were and with significant in the and was an of in the maintenance groups patients in and data are to the are randomised trials or with agents for the maintenance of clinical in patients with CD who or with the same A included trials used the to define clinical with The a time of All were the the the quality of evidence was specific was the in the maintenance Based on is evidence to to or in patients who to induction treatment with any or is a to that and to trials that for the of who from a biologic over the Crohn’s disease patients in clinical under is evidence to for or the of to clinical outcomes as to care from two with a of patients with CD were used to this [Supplementary available as Supplementary data at ECCO-JCC online]. These two of over clinically based for any of our critical clinical [one clinical [one [one [one or [one the a of IBD patients with to maintenance therapy were randomised to or groups were or to a and of the that in patients in clinical a or was in and of in clinical or at were and based the group who received during the patients with CD, with an induction therapy with and were randomised to the following three based on clinical and levels of with of or of or based on clinical The was to a was in clinical with from to in the three in in in studies important in their which the strength of our The outcomes in studies were clinical important such as and to be The in Crohn’s that is on and and that during the induction may outcomes and treatment the that with adequate of patients are Crohn’s disease patients who to an is evidence to for or the of to clinical outcomes to the of in patients on therapy with active to the of of and to clinical was with on clinical in one in a of patients with CD with were randomised to every or based on and levels using the was in clinical the group and the group [Supplementary available as Supplementary data at ECCO-JCC online]. studies a adequate and clinical outcomes from clinical to Based on these observational recent clinical guidelines and a group of experts supported the of the quality of evidence from observational a of patients with active IBD with who and clinical were for and at a of was in of patients in the as with in the clinical was in and in the group another a of the using a of was to a at was this group and a group in which were of was significant in clinical the approach was in the evidence not an a and clinical outcomes a of thiopurines in Crohn’s disease patients in on maintenance as the of is when the treatment is our meta-analysis to the two of in CD patients in on maintenance therapy [Supplementary available as Supplementary data at ECCO-JCC online]. from four trials were included received from to before randomised to or or to or All studies a time of to results that the of clinical is [Supplementary available as Supplementary data at ECCO-JCC online]. meta-analysis for was the data a with of the results were not significant [Supplementary available as Supplementary data at ECCO-JCC online]. for the be performed the data from the To the evidence for the of clinical is in of of as when the treatment was the of was not and from studies that patients treatment for are and this an important research from observational studies and for the of and in patients to treatment with The time and the of patients included in the studies of the meta-analysis are to and that may in the reviewed the literature to the approach of using thiopurines an literature we not evidence the two treatment one was of thiopurines was with thiopurines in the of therapy in patients with IBD. The was as was not to data from and CD specific was patients with Crohn’s disease who with the of and we with A Cochrane based on two the same patients who therapy with or [Supplementary available as Supplementary data at ECCO-JCC online]. The same the of for therapy or These results are to an of in the therapy studies included and studies are to the A of when agents are with the and were as 10 in one meta-analysis of patients included in the patients with Crohn’s disease who with the of and we with the basis of a meta-analysis of studies on by the data included were the and groups to be to the relevant PICO question. The result of this not any in maintenance of clinical therapy and [Supplementary and Supplementary available as Supplementary data at ECCO-JCC online]. this meta-analysis was to of in the studies with a are quality data available for clinical in the which is an that follows the of patients in the on the of were in patients with or at years of The meta-analysis by which was not any in with and therapy [Supplementary available as Supplementary data at ECCO-JCC online]. is evidence to or of therapy in Crohn’s disease patients the to therapy be and and be with the randomised

UNLABELLED: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. MAIN RECOMMENDATIONS: 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett's esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).

BACKGROUND AND AIMS: Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis. PATIENTS AND METHODS: In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses. RESULTS: The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different. CONCLUSIONS: The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.

Abstract Background This review aims to present a consensus for optimal perioperative care in colonic surgery and to provide graded recommendations for items for an evidenced‐based enhanced perioperative protocol. Methods Studies were selected with particular attention paid to meta‐analyses, randomised controlled trials and large prospective cohorts. For each item of the perioperative treatment pathway, available English‐language literature was examined, reviewed and graded. A consensus recommendation was reached after critical appraisal of the literature by the group. Results For most of the protocol items, recommendations are based on good‐quality trials or meta‐analyses of good‐quality trials (quality of evidence and recommendations according to the GRADE system). Conclusions Based on the evidence available for each item of the multimodal perioperative care pathway, the Enhanced Recovery After Surgery (ERAS) Society, International Association for Surgical Metabolism and Nutrition (IASMEN) and European Society for Clinical Nutrition and Metabolism (ESPEN) present a comprehensive evidence‐based consensus review of perioperative care for colonic surgery.

BACKGROUND: Ten to 15% of patients with pouchitis experience refractory or recurrent disease. The aim of this study was to evaluate the effectiveness of a single daily high dose probiotic preparation (VSL#3) in maintaining antibiotic induced remission, and quality of life (QOL), for one year in such patients. METHODS: Patients with pouchitis at least twice in the previous year or requiring continuous antibiotics, associated with a pouchitis disease activity index (PDAI) > or =7 (0 = perfect; 18 = worst), in whom remission was induced by four weeks of combined metronidazole and ciprofloxacin, were randomised to receive VSL#3 6 g or placebo once daily for one year or until relapse. Symptomatic, endoscopic, and histological evaluations were made before, and two and 12 months after randomisation or at the time of relapse. Remission was defined as a clinical PDAI < or =2 and endoscopic PDAI < or =1. Relapse was defined as an increased clinical PDAI score > or =2 and increased endoscopic PDAI score > or =3. QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Thirty six patients were randomised: 20 to VSL#3 and 16 to placebo. Remission was maintained at one year in 17 patients (85%) on VSL#3 and in one patient (6%) on placebo (p<0.0001). The IBDQ score remained high in the VSL#3 group (p = 0.3) but deteriorated in the placebo group (p = 0.0005). CONCLUSION: The once daily high dose probiotic VSL#3 is effective in maintaining antibiotic introduced remission for at least a year in patients with recurrent or refractory pouchitis. This is associated with a high level of quality of life.

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for lower gastrointestinal endoscopy. We recommend that endoscopy services across Europe adopt the following seven key performance measures for lower gastrointestinal endoscopy for measurement and evaluation in daily practice at a center and endoscopist level: <b>1</b> Rate of adequate bowel preparation (minimum standard 90 %); <b>2</b> Cecal intubation rate (minimum standard 90 %); <b>3</b> Adenoma detection rate (minimum standard 25 %); <b>4 </b>Appropriate polypectomy technique (minimum standard 80 %); <b>5</b> Complication rate (minimum standard not set); <b>6</b> Patient experience (minimum standard not set); <b>7</b> Appropriate post-polypectomy surveillance recommendations (minimum standard not set). Other identified performance measures have been listed as less relevant based on an assessment of their importance, scientific acceptability, feasibility, usability, and comparison to competing measures.

BACKGROUND: Germ-line mutations in the base-excision-repair gene MYH have been associated with recessive inheritance of multiple colorectal adenomas. Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:C-->T:A) in the APC gene. METHODS: We screened for germ-line MYH mutations in 152 patients with multiple (3 to 100) colorectal adenomas and 107 APC-mutation-negative probands with classic familial adenomatous polyposis (>100 adenomas). Subgroups were analyzed for changes in the related genes MTH1 and OGG1. Adenomas were tested for somatic APC mutations. RESULTS: Six patients with multiple adenomas and eight patients with polyposis had biallelic germline MYH variants. Missense and protein-truncating mutations were found, and the spectrums of mutations were very similar in the two groups of patients. In the tumors of carriers of biallelic mutations, all somatic APC mutations were G:C-->T:A transversions. In the group with multiple adenomas, about one third of patients with more than 15 adenomas had biallelic MYH mutations. In the polyposis group, no patient with biallelic MYH mutations had severe disease (>1000 adenomas), but three had extracolonic disease. No clearly pathogenic MTH1 or OGG1 mutations were identified. CONCLUSIONS: Germ-line MYH mutations predispose persons to a recessive phenotype, multiple adenomas, or polyposis coli. For patients with about 15 or more colorectal adenomas--especially if no germ-line APC mutation has been identified and the family history is compatible with recessive inheritance--genetic testing of MYH is indicated for diagnosis and calculation of the level of risk in relatives. Clinical care of patients with biallelic MYH mutations should be similar to that of patients with classic or attenuated familial adenomatous polyposis.

BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.