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Crohn Disease: HELP
Articles by Willem A. Bemelman
Based on 33 articles published since 2009
(Why 33 articles?)
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Between 2009 and 2019, W. Bemelman wrote the following 33 articles about Crohn Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline ECCO-ESCP Consensus on Surgery for Crohn's Disease. 2018

Bemelman, Willem A / Warusavitarne, Janindra / Sampietro, Gianluca M / Serclova, Zuzana / Zmora, Oded / Luglio, Gaetano / de Buck van Overstraeten, Anthony / Burke, John P / Buskens, Christianne J / Colombo, Francesco / Dias, Jorge Amil / Eliakim, Rami / Elosua, Tomás / Gecim, I Ethem / Kolacek, Sanja / Kierkus, Jaroslaw / Kolho, Kaija-Leena / Lefevre, Jérémie H / Millan, Monica / Panis, Yves / Pinkney, Thomas / Russell, Richard K / Shwaartz, Chaya / Vaizey, Carolynne / Yassin, Nuha / D'Hoore, André. ·Department of Surgery, Academic Medical Center [AMC], Amsterdam, The Netherlands. · Department of Surgery, St. Mark's Hospital, Harrow, UK. · Department of Surgery, ASST Fatebenefratelli Sacco - Ospedale "Luigi Sacco" Polo Universitario, Milan, Italy. · Department of Surgery, NH Hospital, a.s., Horovice, Czech Republic. · Department of Surgery, Sheba Medical Center, Tel Hashomer, Israel. · Surgical Coloproctology Unit, University of Naples Federico II, Naples, Italy. · Department of Abdominal Surgery, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium. · Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland. · Pediatric Gastroenterology Unit, Hospital S. João [University Hospital], Porto, Portugal. · Department of Gastroenterology and Hepatology, Sheba Medical Center, Tel Hashomer, Israel. · Servicio de Cirugía, Complejo Asistencial Universitario de León, León, Spain. · Colorectal Unit, Ankara University Medical School, Ankara, Turkey. · University Department of Paediatrics and Referral Center for Paediatric Gastroenterology & Nutrition, Children's Hospital Zagreb, Zagreb, Croatia. · Department of Gastroenterology, Hepatology, Feeding Disorders, and Pediatrics, Children's Memorial Health Institute, Warsaw, Poland. · Paediatric Gastroenterology of the Children's Hospital, University of Helsinki, Helsinki, Finland. · Department of General and Digestive Surgery, Hôpital Saint-Antoine and University Paris VI, Paris, France. · Department of Surgery, Hospital Universitari Joan XXIII de Tarragona, Tarragona, Spain. · Department of Colorectal Surgery, Beaujon Hospital [APHP] and University Paris VII Denis-Diderot, Clichy, France. · Academic Department of Surgery, University of Birmingham, Birmingham, UK. · Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, UK. · Department of Surgery, Sheba Medical Center, Ramat Gan, Israel. · IBD Unit, University of Birmingham, Birmingham, St Mark's Hospital, London, UK. ·J Crohns Colitis · Pubmed #28498901.

ABSTRACT: -- No abstract --

2 Guideline A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease. 2014

Gecse, Krisztina B / Bemelman, Willem / Kamm, Michael A / Stoker, Jaap / Khanna, Reena / Ng, Siew C / Panés, Julián / van Assche, Gert / Liu, Zhanju / Hart, Ailsa / Levesque, Barrett G / D'Haens, Geert / Anonymous970798 / Anonymous980798. ·Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Robarts Research Institute, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · St. Vincent's Hospital and University of Melbourne, Melbourne, Australia. · Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Robarts Research Institute, London, Ontario, Canada University of Western Ontario, London, Ontario, Canada. · Department of Medicine and Therapeutics, Institute of Digestive Disease, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, Hong Kong. · Department of Gastroenterology, Hospital Clinic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. · Department of Gastroenterology, University of Leuven, Leuven, Belgium. · Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. · APRG, Imperial College, London, UK IBD Unit, St. Mark's Hospital, London, UK. · Robarts Research Institute, San Diego, CA, USA Division of Gastroenterology, University of California San Diego, La Jolla, California, USA. ·Gut · Pubmed #24951257.

ABSTRACT: OBJECTIVE: To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease (pCD), based on best available evidence. METHODS: Based on a systematic literature review, statements were formed, discussed and approved in multiple rounds by the 20 working group participants. Consensus was defined as at least 80% agreement among voters. Evidence was assessed using the modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. RESULTS: Highest diagnostic accuracy can only be established if a combination of modalities is used. Drainage of sepsis is always first line therapy before initiating immunosuppressive treatment. Mucosal healing is the goal in the presence of proctitis. Whereas antibiotics and thiopurines have a role as adjunctive treatments in pCD, anti-tumour necrosis factor (anti-TNF) is the current gold standard. The efficacy of infliximab is best documented although adalimumab and certolizumab pegol are moderately effective. Oral tacrolimus could be used in patients failing anti-TNF therapy. Definite surgical repair is only of consideration in the absence of luminal inflammation. CONCLUSIONS: Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed.

3 Review Treatment of perianal fistula in Crohn's disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis factor treatment. 2016

de Groof, E J / Sahami, S / Lucas, C / Ponsioen, C Y / Bemelman, W A / Buskens, C J. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. ·Colorectal Dis · Pubmed #26921847.

ABSTRACT: AIM: The introduction of anti-tumour necrosis factor (anti-TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively surgical treatment to one with a much larger emphasis on medical therapy. The aim of this systematic review was to provide an overview of the success rates of setons and anti-TNF for Crohn's perianal fistula. METHOD: Studies evaluating the effect of setons and anti-TNF on Crohn's perianal fistula were included. Studies assessing perianal fistula in children, rectovaginal and rectourinary fistulae were excluded. The primary end-point was the fistula closure rate. Partial closure and recurrence rates were secondary end-points. RESULTS: Ten studies on seton drainage were included (n = 305). Complete closure varied from 13.6% to 100% and recurrence from 0% to 83.3%. In 34 anti-TNF studies (n = 1449), complete closure varied from 16.7% and 93% (partial closure 8.0-91.2%) and recurrence from 8.0% to 40.9%. Four randomized controlled trials (n = 1028) comparing anti-TNF with placebo showed no significant difference in complete or partial closure in meta-analysis (risk difference 0.12, 95% CI -0.06 to 0.30 and 0.09, 95% CI -0.23 to 0.41, respectively). Subgroup analysis (n = 241) showed a significant advantage for complete fistula closure with anti-TNF in two trials with follow-up > 4 weeks (46% vs 13%, P = 0.003 and 30% vs 13%, P = 0.03). Of four included cohort studies, two revealed a significant difference in response in favour of combined treatment (P = 0.001 and P = 0.014). CONCLUSION: Closure and recurrence rates after seton drainage as well as anti-TNF vary widely. Despite a large number of studies, no conclusions can be drawn regarding the preferred strategy. However, combination therapy with (temporary) seton drainage, immunomodulators and anti-TNF may be beneficial in achieving perianal fistula closure.

4 Review Abdominal abscess in Crohn's disease: multidisciplinary management. 2014

de Groof, E Joline / Carbonnel, Frank / Buskens, Christianne J / Bemelman, Willem A. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·Dig Dis · Pubmed #25531361.

ABSTRACT: Crohn's disease (CD) is characterized by full-thickness inflammation of the bowel. For this reason, perforating complications such as intra-abdominal abscesses or fistulas are common. A concomitant intra-abdominal abscess with active CD of the small bowel is a challenging dilemma for gastroenterologists and surgeons. Since there is active and severe disease, this should be treated with immunosuppressive drugs. However, in the presence of an intra-abdominal abscess, immunosuppression can be dangerous. There are several treatment options for intra-abdominal abscesses in CD. Nowadays, the first-line treatment is antibiotic therapy with or without percutaneous drainage. Historically, patients were treated with surgical drainage. With the development of percutaneous drainage, treatment shifted to a more nonsurgical approach. Success rates for percutaneous drainage in the literature vary from 74 to 100%, and it is considered to be a relatively safe procedure. It has been reported that surgery can be avoided after successful percutaneous drainage in a variable number of patients (14-85%). If sepsis is controlled, CD medication should be started to prevent recurrence. It is important to monitor the effect upon CD lesions to avoid further perforating complications. Finally, an undrainable or small abscess can be treated with antibiotics alone, although high recurrence rates have been described with this approach. Patients with a concomitant stenosis, an enterocutaneous fistula or refractory active disease are likely to require surgery. Percutaneous drainage in combination with delayed surgery is useful to improve the patient's condition prior to surgery and is associated with less morbidity, a lower stoma rate and more limited resection. In conclusion, when feasible, percutaneous drainage and antibiotics should be the treatment of choice in patients with an intra-abdominal abscess in CD. If surgery is inevitable, this must be delayed to reduce postoperative septic complications and high stoma rates.

5 Review The surgical intervention: earlier or never? 2014

Bemelman, W A / Allez, M. ·Departments of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: w.a.bemelman@amc.uva.nl. · Department of Gastroenterology, Hôpital Saint-Louis, Paris, France. ·Best Pract Res Clin Gastroenterol · Pubmed #24913388.

ABSTRACT: Crohn's disease (CD) is a chronic and progressive disease characterized by the presence of inflammation in different segments of the digestive tract, resulting in damages of the entire wall. Untreated or treated inappropriately, this eventually might result in stricturing and/or penetrating complications. Traditionally, the first line of treatment is medical, and surgery reserved for those who failed medical therapy. Considerable progresses have been made in the surgical therapy of CD over the past two decades. Some surgical interventions such as those consisting in the resection of long segments or leading to a definitive stoma should be avoided and performed only in case of treatment failure. On the other side, well-indicated and minimal invasive surgery can be considered as an alternative to long-term medical therapy for certain indications. The decision of performing early surgery should take in account the strategy that will be applied post-operatively. Decision making in multidisciplinary teams is paramount.

6 Review Surgery for Crohn's disease: new developments. 2012

Gardenbroek, T J / Tanis, P J / Buskens, C J / Bemelman, W A. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·Dig Surg · Pubmed #22922840.

ABSTRACT: BACKGROUND/AIMS: Crohn's disease is a chronic relapsing inflammatory bowel disease requiring surgery in a large number of patients. This review describes new developments in surgical techniques for treating Crohn's disease. RESULTS: Single-incision laparoscopic surgery decreases abdominal wall trauma by reducing the number of abdominal incisions, possibly improving postoperative results in terms of pain and cosmetics. The resected specimen can be extracted through the single-incision site or the future stoma site. Another option is to use natural orifices for extraction (i.e. transcolonic/transanal), but actual benefits of these procedures have not yet been determined. In patients with extensive perianal disease or rectal involvement, transperineal completion proctectomy is often feasible, thereby avoiding relaparotomy. By using a close rectal intersphincteric resection, damage to the pelvic autonomic nerves is avoided. In addition, the risk of presacral abscess formation is reduced by leaving the mesorectal tissue behind. CONCLUSION: Minimally invasive surgery and associated techniques have become standard clinical practice in surgical treatment of patients with Crohn's disease. New developments aim at further reducing the hospital stay and morbidity, and improving the cosmetic outcomes.

7 Review Decision-making in ileocecal Crohn's disease management: surgery versus pharmacotherapy. 2010

Eshuis, Emma J / Stokkers, Pieter Cf / Bemelman, Willem A. ·Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. e.j.eshuis@amc.uva.nl ·Expert Rev Gastroenterol Hepatol · Pubmed #20350265.

ABSTRACT: Ileocecal Crohn's disease (CD) can be treated medically as well as surgically. Both treatment modalities have been improved markedly in the last two decades, making CD more manageable. However, multidisciplinary research, addressing issues such as timing of surgery or medical treatment versus surgery, is scarce. Particularly in limited ileocecal CD, ileocolic resection might be a good alternative to long-term medical therapy. This review discusses the evidence on medical and surgical treatment options for ileocecal CD. It provides an aid in decision-making by discussing a treatment algorithm that can be used until further evidence on treatment is available.

8 Review [Laparoscopic surgery for inflammatory bowel disease; an update]. 2009

Polle, S W Bas / van Koperen, Paul J / van Berge Henegouwen, Mark I / Slors, J F M Frederik / Stokkers, Pieter C F / Bemelman, Willem A. ·Academisch Medisch Centrum/Universiteit van Amsterdam, Afd. Heelkunde, Amsterdam, The Netherlands. ·Ned Tijdschr Geneeskd · Pubmed #19785860.

ABSTRACT: OBJECTIVE: To carry out a review of the literature for the short- and long-term effects of various laparoscopic operations in the inflammatory bowel diseases ulcerative colitis and Crohn's disease and to compare these operations with open surgical procedures. DESIGN: Review of the literature. METHOD: PubMed (Medline), Embase and Cochrane databases were searched for randomised clinical trials and meta-analyses on this topic, published between January 1991 and August 2008. If no level A1, A2 or A2B studies were found, we searched for the best available evidence. RESULTS: For Crohn's disease, there was level A2 evidence that, in comparison with open surgery, in experienced hands laparoscopic ileocaecal resection enhanced recovery and led to a shorter hospital stay and lower costs. Following laparoscopic surgery, subjective body image and cosmetic appearance scores were higher, when compared in the long term. In patients with ulcerative colitis, the expected benefits of laparoscopic proctocolectomy have not yet been demonstrated in a randomised study. Although there was a trend towards a reduced hospital stay (1.6 days) when laparoscopy proctocolectomy was performed, the operating time was 1.5 h longer than in conventional surgery. Body image and cosmetic appearance scores were also higher here when compared in the long term. CONCLUSION: Laparoscopic ileocaecal resection is preferable in Crohn's disease, provided that it is performed in a centre with sufficient expertise in laparoscopic surgery. In patients with ulcerative colitis, laparoscopic proctocolectomy with construction of an ileoanal pouch is indicated in young active patients who are concerned for their appearance. Given its complexity, this operation should be performed only in specialist centres.

9 Clinical Trial Evaluation of conventional, dynamic contrast enhanced and diffusion weighted MRI for quantitative Crohn's disease assessment with histopathology of surgical specimens. 2014

Tielbeek, Jeroen A W / Ziech, Manon L W / Li, Zhang / Lavini, Cristina / Bipat, Shandra / Bemelman, Willem A / Roelofs, Joris J T H / Ponsioen, Cyriel Y / Vos, Frans M / Stoker, Jaap. ·Academic Medical Center, Department of Radiology, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands, j.a.w.tielbeek@amc.uva.nl. ·Eur Radiol · Pubmed #24037299.

ABSTRACT: OBJECTIVES: To prospectively compare conventional MRI sequences, dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging (DWI) with histopathology of surgical specimens in Crohn's disease. METHODS: 3-T MR enterography was performed in consecutive Crohn's disease patients scheduled for surgery within 4 weeks. One to four sections of interest per patient were chosen for analysis. Evaluated parameters included mural thickness, T1 ratio, T2 ratio; on DCE-MRI maximum enhancement (ME), initial slope of increase (ISI), time-to-peak (TTP); and on DWI apparent diffusion coefficient (ADC). These were compared with location-matched histopathological grading of inflammation (AIS) and fibrosis (FS) using Spearman correlation, Kruskal-Wallis and Chi-squared tests. RESULTS: Twenty patients (mean age 38 years, 12 female) were included and 50 sections (35 terminal ileum, 11 ascending colon, 2 transverse colon, 2 descending colon) were matched to AIS and FS. Mural thickness, T1 ratio, T2 ratio, ME and ISI correlated significantly with AIS, with moderate correlation (r = 0.634, 0.392, 0.485, 0.509, 0.525, respectively; all P < 0.05). Mural thickness, T1 ratio, T2 ratio, ME, ISI and ADC correlated significantly with FS (all P < 0.05). CONCLUSIONS: Quantitative parameters from conventional, DCE-MRI and DWI sequences correlate with histopathological scores of surgical specimens. DCE-MRI and DWI parameters provide additional information. KEY POINTS: • Conventional MR enterography can be used to assess Crohn's disease activity. • Several MRI parameters correlate with inflammation and fibrosis scores from histopathology. • Dynamic contrast enhanced imaging and diffusion weighted imaging give additional information. • Quantitative MRI parameters can be used as biomarkers to evaluate Crohn's disease activity.

10 Article Inclusion of the Mesentery in Ileocolic Resection for Crohn's Disease is Associated with Reduced Surgical Recurrence: Editorial by Coffey et al. 2018

Buskens, Christianne J / Bemelman, Willem A. ·Department of Surgery, Academic Medical Center, University Medical Center Amsterdam, Netherlands. ·J Crohns Colitis · Pubmed #30137343.

ABSTRACT: -- No abstract --

11 Article Fibrostenotic Phenotype of Myofibroblasts in Crohn's Disease is Dependent on Tissue Stiffness and Reversed by LOX Inhibition. 2018

de Bruyn, Jessica R / van den Brink, Gijs R / Steenkamer, Jessica / Buskens, Christianne J / Bemelman, Willem A / Meisner, Sander / Muncan, Vanesa / Te Velde, Anje A / D'Haens, Geert R / Wildenberg, Manon E. ·Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. · Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·J Crohns Colitis · Pubmed #29672662.

ABSTRACT: Background and Aims: Crohn's disease is a chronic inflammatory disorder of the intestine and often leads to fibrosis, characterized by excess extracellular matrix [ECM] deposition, increased tissue stiffness, and stricture formation. Here we evaluated the contribution of myofibroblast-ECM interactions to the development of intestinal fibrosis in Crohn's disease. Methods: Matched primary human myofibroblasts were isolated from stenotic, inflamed and normal-appearing small intestine within the same Crohn's disease patient [n = 10]. Cells were analyzed by gene expression profiling, microscopy and functional assays, including matrix metalloproteinase [MMP] production and ECM contraction. Results: We demonstrated that myofibroblasts isolated from stenotic intestine differed both in phenotype and function from those isolated from purely inflammatory or normal-appearing intestine of the same patient. Stenotic myofibroblasts displayed increased expression of genes associated with ECM modulation and collagen deposition. Upon culture in a fibrotic environment, normal myofibroblasts increased expression of MMPs to counteract the mechanical force exerted by the matrix. Interestingly, stenotic myofibroblasts showed a paradoxical response with decreased expression of MMP3. In addition, stenotic myofibroblasts expressed increased levels of the collagen crosslinking enzyme lysyl oxidase [LOX] and induced significantly more ECM contraction than both normal and inflamed myofibroblasts. Importantly, LOX inhibition completely restored MMP3 activity in stenotic myofibroblasts grown in a fibrotic environment, and prevented excessive ECM contraction. Conclusions: Together these data indicate aberrancies in the myofibroblast-ECM interaction in Crohn's disease, and identify LOX inhibition as a potential anti-fibrotic agent in this condition.

12 Article Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease. 2018

de Bruyn, Jessica R / Becker, Marte A / Steenkamer, Jessica / Wildenberg, Manon E / Meijer, Sybren L / Buskens, Christianne J / Bemelman, Willem A / Löwenberg, Mark / Ponsioen, Cyriel Y / van den Brink, Gijs R / D'Haens, Geert R. ·Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. · Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. · Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·PLoS One · Pubmed #29364909.

ABSTRACT: INTRODUCTION: Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. METHODS: In a previous trial, patients with ileocecal Crohn's disease were randomized to either immediate ileocecal resection or medical treatment with Infliximab. In case of insufficient response to Infliximab, the latter underwent secondary ileocecal resection. We compared specimens from those patients undergoing immediate resection (Infliximab naïve, n = 20) to those who failed Infliximab therapy (n = 20). RESULTS: Infliximab naïve and Infliximab failure patients had similar severity of inflammation when assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D'Haens-score, median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin depositions were increased in patients previously exposed to Infliximab compared to patients naïve to Infliximab. On mRNA level, procollagen peptidase showed significantly more mucosal mRNA expression in Crohn's disease patients who failed Infliximab. Infliximab responders showed no increase of this marker after 4 weeks of successful Infliximab treatment. DISCUSSION: Failure to Infliximab therapy is associated with subclinical fibrosis in Crohn's disease.

13 Article Single port laparoscopic ileocaecal resection for Crohn's disease: a multicentre comparison with multi-port laparoscopy. 2018

Carvello, M / de Groof, E J / de Buck van Overstraeten, A / Sacchi, M / Wolthuis, A M / Buskens, C J / D'Hoore, A / Bemelman, W A / Spinelli, A. ·Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium. · Department of Biomedical Science, Humanitas University, Rozzano, Milan, Italy. ·Colorectal Dis · Pubmed #28622435.

ABSTRACT: AIM: Single port (SP) ileocaecal resection (ICR) is an established technique but there are no large studies comparing SP and multi-port (MP) laparoscopic surgery in Crohn's disease (CD). The aim of this study was to compare postoperative pain scores and analgesia requirements after SP and MP laparoscopic ICR for CD. METHOD: This was a retrospective study of patients undergoing SP or MP ICR for CD in three tertiary referral centres from February 1999 to October 2014. Baseline characteristics (age, sex, body mass index and indication for surgery) were compared. Primary end-points were postoperative pain scores, analgesia requirements and short-term postoperative outcomes. RESULTS: SP ICR (n = 101) and MP ICR (n = 156) patients were included in the study. Visual analogue scale scores were significantly lower after SP ICR on postoperative day 1 (P = 0.016) and day 2 (P = 0.04). Analgesia requirements were significantly reduced on postoperative day 2 in the SP group compared with the MP group (P = 0.007). Duration of surgery, conversion to open surgery and stoma rates were comparable between the two groups. Surgery was more complex in terms of additional procedures when MP was adopted (P = 0.001). There were no differences in postoperative complication rates, postoperative food intake, length of stay and readmissions. CONCLUSION: These data suggest that in comparison to standard laparoscopic surgery SP ICR might be less painful and patients might require less opioid analgesia.

14 Article Establishing Key Performance Indicators [KPIs] and Their Importance for the Surgical Management of Inflammatory Bowel Disease-Results From a Pan-European, Delphi Consensus Study. 2017

Morar, Pritesh S / Hollingshead, James / Bemelman, Willem / Sevdalis, Nick / Pinkney, Thomas / Wilson, Graeme / Dunlop, Malcolm / Davies, R Justin / Guy, Richard / Fearnhead, Nicola / Brown, Steven / Warusavitarne, Janindra / Edwards, Cathryn / Faiz, Omar. ·Surgical Epidemiology, Trials and Outcome Centre (SETOC), St. Mark's Hospital and Academic Institute, London, United Kingdom. · Department of Surgery and Cancer, Imperial College, London, United Kingdom. · Department of Surgery, Amsterdam Medical Centre, Amsterdam, Netherlands. · Centre for Implementation Science, King's College, London, United Kingdom. · Inflammatory Bowel Disease (IBD) subcommittee of Association of Coloproctology of Great Britain and Ireland (ACPGBI), London, United Kingdom. · Inflammatory Bowel Disease (IBD) Clinical Advisory Group (CAG), Association of Coloproctology of Great Britain and Ireland (ACPGBI), London, United Kingdom. · South Devon NHS Foundation Trust, Torbay. ·J Crohns Colitis · Pubmed #28961891.

ABSTRACT: Background and Aims: Key performance indicators [KPIs] exist across a range of areas in medicine. They help to monitor outcomes, reduce variation, and drive up standards across services. KPIs exist for inflammatory bowel disease [IBD] care, but none specifically cover inflammatory bowel disease [IBD] surgical service provision. Methods: This was a consensus-based study using a panel of expert IBD clinicians from across Europe. Items were developed and fed through a Delphi process to achieve consensus. Items were ranked on a Likert scale from 1 [not important] to 5 [very important]. Consensus was defined when the inter quartile range was ≤ 1, and items with a median score > 3 were considered for inclusion. Results: A panel of 21 experts [14 surgeons and 7 gastroenterologists] was recruited. Consensus was achieved on procedure-specific KPIs for ileocaecal and perianal surgery for Crohn's disease, [N = 10] with themes relating to morbidity [N = 7], multidisciplinary input [N = 2], and quality of life [N = 1]; and for subtotal colectomy, proctocolectomy and ileoanal pouch surgery for ulcerative colitis [N = 11], with themes relating to mortality [N = 2], morbidity [N = 8], and service provision [N = 1]. Consensus was also achieved for measures of the quality of IBD surgical service provision and quality assurance in IBD surgery. Conclusions: This study has provided measurable KPIs for the provision of surgical services in IBD. These indicators cover IBD surgery in general, the governance and structures of the surgical services, and separate indicators for specific subareas of surgery. Monitoring of IBD services with these KPIs may reduce variation across services and improve quality.

15 Article Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. 2017

Ponsioen, Cyriel Y / de Groof, E Joline / Eshuis, Emma J / Gardenbroek, Tjibbe J / Bossuyt, Patrick M M / Hart, Ailsa / Warusavitarne, Janindra / Buskens, Christianne J / van Bodegraven, Ad A / Brink, Menno A / Consten, Esther C J / van Wagensveld, Bart A / Rijk, Marno C M / Crolla, Rogier M P H / Noomen, Casper G / Houdijk, Alexander P J / Mallant, Rosalie C / Boom, Maarten / Marsman, Willem A / Stockmann, Hein B / Mol, Bregje / de Groof, A Jeroen / Stokkers, Pieter C / D'Haens, Geert R / Bemelman, Willem A / Anonymous7511303. ·Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Netherlands. · Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Netherlands; Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands. · Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands. · Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, Amsterdam, Netherlands. · Inflammatory Bowel Disease Unit, St Mark's Hospital, London, UK. · Department of Surgery, St Mark's Hospital, London, UK. · Department of Gastroenterology and Hepatology, Zuyderland Hospital, Sittard, Netherlands; VU University Medical Centre, Amsterdam, Netherlands. · Department of Gastroenterology and Hepatology, Meander Medical Centre, Amersfoort, Netherlands. · Department of Surgery, Meander Medical Centre, Amersfoort, Netherlands. · Department of Surgery, OLVG West, Amsterdam, Netherlands. · Department of Gastroenterology and Hepatology, Amphia Hospital, Breda, Netherlands. · Department of Surgery, Amphia Hospital, Breda, Netherlands. · Department of Gastroenterology and Hepatology, Medical Centre Alkmaar, Alkmaar, Netherlands. · Department of Surgery, Medical Centre Alkmaar, Alkmaar, Netherlands. · Department of Gastroenterology and Hepatology, Flevo Hospital, Almere, Netherlands. · Department of Surgery, Flevo Hospital, Almere, Netherlands. · Department of Gastroenterology, Kennemer Gasthuis, Haarlem, Netherlands. · Department of Surgery, Kennemer Gasthuis, Haarlem, Netherlands. · Department of Gastroenterology and Hepatology, OLVG West, Amsterdam, Netherlands. · Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands. Electronic address: w.a.bemelman@amc.uva.nl. ·Lancet Gastroenterol Hepatol · Pubmed #28838644.

ABSTRACT: BACKGROUND: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. METHODS: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). FINDINGS: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. INTERPRETATION: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. FUNDING: Netherlands Organisation for Health Research and Development.

16 Article Short- and medium-term outcomes following primary ileocaecal resection for Crohn's disease in two specialist centres. 2017

de Buck van Overstraeten, A / Eshuis, E J / Vermeire, S / Van Assche, G / Ferrante, M / D'Haens, G R / Ponsioen, C Y / Belmans, A / Buskens, C J / Wolthuis, A M / Bemelman, W A / D'Hoore, A. ·Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Belgium. · Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Belgium. · KU Leuven-University of Leuven and Universiteit Hasselt, I-Biostat, Leuven, Belgium. · General Surgery, Academic Medical Centre, Amsterdam, The Netherlands. ·Br J Surg · Pubmed #28745410.

ABSTRACT: BACKGROUND: Despite improvements in medical therapy, the majority of patients with Crohn's disease still require surgery. The aim of this study was to report safety, and clinical and surgical recurrence rates, including predictors of recurrence, after ileocaecal resection for Crohn's disease. METHODS: This was a cohort analysis of consecutive patients undergoing a first ileocaecal resection for Crohn's disease between 1998 and 2013 at one of two specialist centres. Anastomotic leak rate and associated risk factors were assessed. Kaplan-Meier estimates were used to describe long-term clinical and surgical recurrence. Univariable and multivariable regression analyses were performed to identify risk factors for both endpoints. RESULTS: In total, 538 patients underwent primary ileocaecal resection (40·0 per cent male; median age at surgery 31 (i.q.r. 24-42) years). Median follow-up was 6 (2-9) years. Fifteen of 507 patients (3·0 per cent) developed an anastomotic leak. An ASA fitness grade of III (odds ratio (OR) 4·34, 95 per cent c.i. 1·12 to 16·77; P = 0·033), preoperative antitumour necrosis factor therapy (OR 3·30, 1·09 to 9·99; P = 0·035) and length of resected bowel specimen (OR 1·06, 1·03 to 1·09; P < 0·001) were significant risk factors for anastomotic leak. Rates of clinical recurrence were 17·6, 45·4 and 55·0 per cent after 1, 5 and 10 years respectively. Corresponding rates of requirement for further surgery were 0·6, 6·5 and 19·1 per cent. Smoking (hazard ratio (HR) 1·67, 95 per cent c.i. 1·14 to 2·43; P = 0·008) and a positive microscopic resection margin (HR 2·16, 1·46 to 3·21; P < 0·001) were independent risk factors for clinical recurrence. Microscopic resection margin positivity was also a risk factor for further surgery (HR 2·99, 1·36 to 6·54; P = 0·006). CONCLUSION: Ileocaecal resection achieved durable medium-term remission, but smoking and resection margin positivity were risk factors for recurrence.

17 Article Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease. 2017

Doorenspleet, M E / Westera, L / Peters, C P / Hakvoort, T B M / Esveldt, R E / Vogels, E / van Kampen, A H C / Baas, F / Buskens, C / Bemelman, W A / D'Haens, G / Ponsioen, C Y / Te Velde, A A / de Vries, N / van den Brink, G R. ·Amsterdam Rheumatology and immunology Center, Academic Medical Center, Amsterdam, The Netherlands. · Laboratory for Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands. · Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. · Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherland. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·J Crohns Colitis · Pubmed #28158397.

ABSTRACT: Background and Aim: T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy. Methods: Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease. From this cohort, additional biopsies were taken after 8 weeks of remission induction therapy from eight responders and eight non-responders. Control biopsies from 11 patients without inflammatory bowel disease [IBD] were included. The TCRβ repertoire was analysed by next-generation sequencing of biopsy RNA. Results: Both in Crohn's disease patients and in non-IBD controls, a broad intestinal T-cell repertoire was found, with a considerable part consisting of expanded clones. Clones in Crohn's disease were more expanded [p = 0.008], with the largest clones representing up to as much as 58% of the total repertoire. There was a substantial overlap of the repertoire between inflamed and uninflamed tissue and between ileum and colon. Following therapy, responders showed larger changes in the T-cell repertoire than non-responders, although a considerable part of the repertoire remained unchanged in both groups. Conclusions: The intestinal T-cell repertoire distribution in Crohn's disease is different from that in the normal gut, containing profoundly expanded T-cell clones that take up a large part of the repertoire. The T-cell repertoire is fairly stable regardless of endoscopic mucosal inflammation or response to therapy.

18 Article The association between intensified medical treatment, time to surgery and ileocolic specimen length in Crohn's disease. 2017

de Groof, E J / Gardenbroek, T J / Buskens, C J / Tanis, P J / Ponsioen, C Y / D'Haens, G R A M / Bemelman, W A. ·Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands. ·Colorectal Dis · Pubmed #27883259.

ABSTRACT: AIM: During the last decade, treatment protocols have changed for patients with ileocolic Crohn's disease. Anti-tumour necrosis factor (anti-TNF) has become part of standard medical treatment, usually in a step-up approach. The aim was to analyse if improved medical treatment has resulted in more limited ileocolic resections and a longer interval between diagnosis and surgery. METHOD: Patients undergoing ileocolic resection for Crohn's disease were included (1999-2014). Patient characteristics were compared to the results of a population-based study (between 2004 and 2010) previously performed in the catchment area of the present tertiary referral centre. Time trends were analysed using the Cochrane-Armitage trend, Spearman's correlation coefficient and linear regression. RESULTS: In total, 195 patients undergoing ileocolic resection were included. Patient characteristics were not significantly different from the background cohort, confirming a representative study group. Sixty-three patients were men (32.3%, median age at surgery 30.0 years, interquartile range 23.0-40.0). Anti-TNF and immunomodulator use prior to surgery increased significantly during the study period (χ CONCLUSION: This study demonstrated that over time patients with ileocolic Crohn's disease who eventually underwent ileocolic resection have been treated more intensively medically; however, this did not result in reduced specimen size.

19 Article External validation of a prognostic model of preoperative risk factors for failure of restorative proctocolectomy. 2017

Sahami, S / Bartels, S A L / D'Hoore, A / Young Fadok, T / Tanis, P J / de Buck van Overstraeten, A / Wolthuis, A M / Buskens, C J / Bemelman, W A. ·Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, University Hospitals Leuven, Leuven, Belgium. · Department of Surgery, Mayo Clinic College of Medicine, Phoenix, Arizona, USA. ·Colorectal Dis · Pubmed #27315787.

ABSTRACT: AIM: The Cleveland Clinic has proposed a prognostic model of preoperative risk factors for failure of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis. The model incorporates four predictive variables: completion proctectomy, handsewn anastomosis, diabetes mellitus and Crohn's disease. The aim of the present study was to perform an external validation of this model in a new cohort of patients who had RPC. METHOD: Validation was performed in a multicentre cohort of 747 consecutive patients who had an RPC between 1990 and 2015 in three tertiary-care facilities, using a Kaplan-Meier survival analysis and Cox regression analysis. The performance of the model was expressed using the Harrell concordance error rate. The primary outcome measure was pouch survival with maintenance of anal function. RESULTS: During the study period, 45 (6.0%) patients experienced failure at a median interval of 31 months (interquartile range 9-82 months) from the original RPC. Multivariable analysis showed handsewn anastomosis to be the only significant independent predictor. The Harrell concordance error rate was 0.42, indicating poor performance. Anastomotic leakage and Crohn's disease of the pouch were strong postoperative predictors for pouch failure and showed a significant difference in pouch survival after 10 years (P < 0.001). CONCLUSION: The poor performance of the Cleveland Clinic prognostic model makes it unsuitable for daily clinical practice. Handsewn anastomosis was associated with pouch failure in our cohort with relatively few events. A prediction model for anastomotic leakage or Crohn's disease of the pouch may be a better solution since these variables are strongly associated with pouch failure.

20 Article European Crohn's and Colitis Organisation Topical Review on Prediction, Diagnosis and Management of Fibrostenosing Crohn's Disease. 2016

Rieder, Florian / Latella, Giovanni / Magro, Fernando / Yuksel, Elif S / Higgins, Peter D R / Di Sabatino, Antonio / de Bruyn, Jessica R / Rimola, Jordi / Brito, Jorge / Bettenworth, Dominik / van Assche, Gert / Bemelman, Willem / d'Hoore, Andre / Pellino, Gianluca / Dignass, Axel U. ·Department of Pathobiology, Lerner Research Institute, Cleveland, OH, USA Department of Gastroenterology, Hepatology & Nutrition, Lerner Research Institute, Cleveland, OH, USA riederf@ccf.org. · Department of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L'Aquila, L'Aquila, Italy. · Department of Pharmacology & Therapeutics, Department of Gastroenterology, Faculty of Medicine University of Porto, Porto, Portugal. · Department of Gastroenterology, Izmir Ataturk Teaching and Research Hospital-Katip Celebi University, Izmir, Turkey. · Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA. · First Department of Internal Medicine, St Matteo Hospital Foundation, University of Pavia, Pavia, Italy. · Academic Medical Center Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands. · Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain. · Department of Radiology, Centro Hospitalar do Algarve, Lagos, Portugal. · Department of Medicine B, University Hospital of Münster, Münster, Germany. · Division of Gastroenterology, University of Leuven, Leuven, Belgium. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Abdominal Surgery, University Hospital Gasthuisberg, Leuven, Belgium. · Department of Medicine 1, Agaplesion Markus Hospital, Frankfurt, Germany. · Department of Pathobiology, Lerner Research Institute, Cleveland, OH, USA. ·J Crohns Colitis · Pubmed #26928961.

ABSTRACT: This ECCO topical review of the European Crohn's and Colitis Organisation [ECCO] focused on prediction, diagnosis, and management of fibrostenosing Crohn's disease [CD]. The objective was to achieve evidence-supported, expert consensus that provides guidance for clinical practice.

21 Article Results of the Fifth Scientific Workshop of the ECCO [II]: Clinical Aspects of Perianal Fistulising Crohn's Disease-the Unmet Needs. 2016

Gecse, Krisztina B / Sebastian, Shaji / Hertogh, Gert de / Yassin, Nuha A / Kotze, Paulo G / Reinisch, Walter / Spinelli, Antonino / Koutroubakis, Ioannis E / Katsanos, Konstantinos H / Hart, Ailsa / van den Brink, Gijs R / Rogler, Gerhard / Bemelman, Willem A. ·First Department of Medicine, Semmelweis University, Budapest, Hungary krisztina.gecse@gmail.com. · Inflammatory Bowel Disease Unit, Hull & East Yorkshire NHS Trust, Hull, UK. · Department of Pathology, University of Leuven, Leuven, Belgium. · Department of Colorectal Surgery, St Mark's Hospital and Academic Institute, London, UK. · Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, PR, Brazil. · Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, ON, Canada. · Colorectal Surgery Unit, Humanitas Research Hospital, Humanitas University, Milan, Italy. · Department of Gastroenterology, University Hospital Heraklion, Iraklio, Greece. · Division of Gastroenterology, Department of Medicine, School of Health Sciences, Ioannina, Greece. · Inflammatory Bowel Disease Unit, St Mark's Hospital, London, UK. · Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ·J Crohns Colitis · Pubmed #26826183.

ABSTRACT: BACKGROUND AND AIMS: Perianal fistulas affect up to one-third of Crohn's patients during the course of their disease. Despite the considerable disease burden, current treatment options remain unsatisfactory. The Fifth Scientific Workshop [SWS5] of the European Crohn's and Colitis Organisation [ECCO] focused on the pathophysiology and clinical impact of fistulas in the disease course of patients with Crohn's disease [CD]. METHODS: The ECCO SWS5 Working Group on clinical aspects of perianal fistulising Crohn's disease [pCD] consisted of 13 participants, gastroenterologists, colorectal surgeons, and a histopathologist, with expertise in the field of inflammatory bowel diseases. A systematic review of literature was performed. RESULTS: Four main areas of interest were identified: natural history of pCD, morphological description of fistula tracts, outcome measures [including clinical and patient-reported outcome measures, as well as magnetic resonance imaging] and randomised controlled trials on pCD. CONCLUSIONS: The treatment of perianal fistulising Crohn's disease remains a multidisciplinary challenge. To optimise management, a reliable classification and proper trial endpoints are needed. This could lead to standardised diagnosis, treatment, and follow-up of Crohn's perianal fistulas and the execution of well-designed trials that provide clear answers. The prevalence and the natural history of pCD need further evaluation.

22 Article Multimodal treatment of perianal fistulas in Crohn's disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial. 2015

de Groof, E Joline / Buskens, Christianne J / Ponsioen, Cyriel Y / Dijkgraaf, Marcel G W / D'Haens, Geert R A M / Srivastava, Nidhi / van Acker, Gijs J D / Jansen, Jeroen M / Gerhards, Michael F / Dijkstra, Gerard / Lange, Johan F M / Witteman, Ben J M / Kruyt, Philip M / Pronk, Apollo / van Tuyl, Sebastiaan A C / Bodelier, Alexander / Crolla, Rogier M P H / West, Rachel L / Vrijland, Wietske W / Consten, Esther C J / Brink, Menno A / Tuynman, Jurriaan B / de Boer, Nanne K H / Breukink, Stephanie O / Pierik, Marieke J / Oldenburg, Bas / van der Meulen, Andrea E / Bonsing, Bert A / Spinelli, Antonino / Danese, Silvio / Sacchi, Matteo / Warusavitarne, Janindra / Hart, Ailsa / Yassin, Nuha A / Kennelly, Rory P / Cullen, Garret J / Winter, Desmond C / Hawthorne, A Barney / Torkington, Jared / Bemelman, Willem A. ·Department of Surgery, Academic Medical Center, PO Box 22660, 1100, DD, Amsterdam, The Netherlands. e.j.degroof@amc.uva.nl. · Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. e.j.degroof@amc.uva.nl. · Department of Surgery, Academic Medical Center, PO Box 22660, 1100, DD, Amsterdam, The Netherlands. c.j.buskens@amc.uva.nl. · Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.y.ponsioen@amc.uva.nl. · Clinical Research Unit, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.g.dijkgraaf@amc.uva.nl. · Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. g.dhaens@amc.uva.nl. · Department of Gastroenterology and Hepatology, Medical Center Haaglanden, Lijnbaan 32, 2512 VA Den Haag, The Netherlands. n.srivastava@mchaaglanden.nl. · Department of Surgery, Medical Center Haaglanden, Lijnbaan 32, 2512 VA Den Haag, The Netherlands. g.van.acker@mchaaglanden.nl. · Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1091 AC Amsterdam, The Netherlands. j.m.jansen@olvg.nl. · Department of Surgery, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1091 AC Amsterdam, The Netherlands. m.f.gerhards@olvg.nl. · Department of Gastroenterology and Hepatology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. g.dijkstra@int.umcg.nl. · Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. j.lange@umcg.nl. · Department of Gastroenterology and Hepatology, Hospital Gelderse Vallei, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands. WittemanB@zgv.nl. · Department of Surgery, Hospital Gelderse Vallei, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands. KruytF@zgv.nl. · Department of Surgery, Diakonessenhuis Utrecht, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands. APronk@diakhuis.nl. · Department of Gastroenterology and Hepatology, Diakonessenhuis Utrecht, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands. bvtuyl@diakhuis.nl. · Department of Gastroenterology and Hepatology, Amphia Hospital, Molengracht 21, 4818 CK Breda, The Netherlands. abodelier@amphia.nl. · Department of Surgery, Amphia Hospital, Molengracht 21, 4818 CK Breda, The Netherlands. · Department of Gastroenterology and Hepatology, St Franciscus Gasthuis, Kleiweg 500, 3045 PM Rotterdam, The Netherlands. r.west@sfg.n. · Department of Surgery, St Franciscus Gasthuis, Kleiweg 500, 3045 PM Rotterdam, The Netherlands. w.vrijland@sfg.nl. · Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ Amersfoort, The Netherlands. ecj.consten@meandermc.nl. · Department of Gastroenterology and Hepatology, Meander Medical Center, Maatweg 3, 3813 TZ Amersfoort, The Netherlands. ma.brink@meandermc.nl. · Department of Surgery, VU Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. j.tuynman@vumc.nl. · Department of Gastroenterology and Hepatology, VU Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. KHN.deBoer@vumc.nl. · Department of Surgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. s.breukink@mumc.nl. · Department of Gastroenterology and Hepatology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. m.pierik@mumc.nl. · Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. b.oldenburg@umcutrecht.nl. · Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. ae.meulen@lumc.nl. · Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. B.A.Bonsing@lumc.nl. · Department of Surgery, Humanitas Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano MI, Milan, Italy. antonino.spinelli@humanitas.it. · Department of Gastroenterology and Hepatology, Humanitas Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano MI, Milan, Italy. silvio.danese@humanitas.it. · Department of Surgery, Humanitas Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano MI, Milan, Italy. matteo.sacchi@humanitas.it. · Department of Surgery, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, London, UK. j.warusavitarne@nhs.net. · Department of Gastroenterology and Hepatology, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, London, England. ailsa.hart@nhs.net. · Department of Surgery, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, London, UK. nuhayassin@nhs.net. · Department of Surgery, St Vincent's Healthcare Group, Elm Park, Merrion Rd, Dublin 4, Ireland. rorykennelly@rcsi.ie. · Department of Gastroenterology and Hepatology, St Vincent's Healthcare Group, Elm Park, Merrion Rd, Dublin 4, Ireland. g.cullen@st-vincents.ie. · Department of Surgery, St Vincent's Healthcare Group, Elm Park, Merrion Rd, Dublin 4, Ireland. des.winter@gmail.com. · Department of Gastroenterology and Hepatology, Spire Cardiff Hospital, Glamorgan House, Croescadarn Rd, Cardiff, South Glamorgan CF23 8XL, UK. Barney.Hawthorne@wales.nhs.uk. · Department of Surgery, Spire Cardiff Hospital, Glamorgan House, Croescadarn Rd, Cardiff, South Glamorgan CF23 8XL, England. Jared.Torkington@wales.nhs.uk. · Department of Surgery, Academic Medical Center, PO Box 22660, 1100, DD, Amsterdam, The Netherlands. w.a.bemelman@amc.uva.nl. ·Trials · Pubmed #26289163.

ABSTRACT: BACKGROUND: Currently there is no guideline for the treatment of patients with Crohn's disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs. METHODS/DESIGN: This is a multicentre, randomized controlled trial. Patients with Crohn's disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs. DISCUSSION: The PISA trial is a multicentre, randomised controlled trial of patients with Crohn's disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters. TRIAL REGISTRATION: Nederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).

23 Article Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria. 2015

Bernink, Jochem H / Krabbendam, Lisette / Germar, Kristine / de Jong, Esther / Gronke, Konrad / Kofoed-Nielsen, Michael / Munneke, J Marius / Hazenberg, Mette D / Villaudy, Julien / Buskens, Christianne J / Bemelman, Willem A / Diefenbach, Andreas / Blom, Bianca / Spits, Hergen. ·Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. · Research Center Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67 D-55131 Mainz, Germany. · Department of Hematology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. · Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. · Department of Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. · Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: hergen.spits@amc.uva.nl. ·Immunity · Pubmed #26187413.

ABSTRACT: Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn's disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.

24 Article Prolonged preoperative hospital stay is a risk factor for complications after emergency colectomy for severe colitis. 2013

Bartels, S A L / Gardenbroek, T J / Bos, L / Ponsioen, C Y / D'Haens, G R A M / Tanis, P J / Buskens, C J / Bemelman, W A. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·Colorectal Dis · Pubmed #23810064.

ABSTRACT: AIM: Risk factors for postoperative complications in patients undergoing emergency colectomy for severe colitis in inflammatory bowel disease have hardly been studied. Therefore, this study aimed to define predictors of a complicated postoperative course in these patients. METHOD: A retrospective review was performed of 71 consecutive patients who underwent emergency colectomy for severe colitis between 1999 and 2012 at a tertiary referral centre. Complications were graded according to the Clavien-Dindo classification. Patients with a complication Grade II or higher were compared with those with no complications or a Grade I complication. RESULTS: Nineteen patients (26.7%) had at least one postoperative complication classified as Clavien-Dindo Grade II or higher. In the group with postoperative complications, patients had a higher age (mean 45 vs 35 years, P = 0.020) and a higher body mass index (BMI) (mean 25.9 vs 21.0 kg/m(2), P = 0.006). Length of preoperative hospital stay (median 15 vs 6 days, P = 0.032) was longer in the group with postoperative complications. During the study period, the preoperative hospital stay decreased by 0.8 days per study year (95% CI 0.2-1.5 days, P < 0.001). This did not influence the complication rate over time, however. CONCLUSION: Factors increasing the risk of complications after emergency colectomy for severe colitis were a higher age, a higher BMI and a longer preoperative hospital stay.

25 Article Ten years of infliximab for Crohn's disease: outcome in 469 patients from 2 tertiary referral centers. 2013

Eshuis, Emma J / Peters, Charlotte P / van Bodegraven, Adriaan A / Bartelsman, Joep F / Bemelman, Willem / Fockens, Paul / D'Haens, Geert R A M / Stokkers, Pieter C F / Ponsioen, Cyriel Y. ·Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. ·Inflamm Bowel Dis · Pubmed #23552767.

ABSTRACT: BACKGROUND: Aim was to assess the long-term clinical efficacy of infliximab therapy in patients with Crohn's disease treated in a cohort of 2 tertiary referral centers in the Netherlands. METHODS: All consecutive patients with Crohn's disease treated with infliximab were assessed. Endpoints were primary clinical efficacy, sustained benefit, efficacy of retreatment, surgical intervention rates, and safety. Sustained benefit was determined by Kaplan-Meier analysis. The estimated 5-year benefit was calculated. RESULTS: A total of 469 patients were included. Median follow-up length was 4.5 years (interquartile range, 2.7-6.8). Seventy patients (15%) had unsuccessful remission induction, and 316 patients received maintenance therapy. Scheduled maintenance regimen was successful in 169 of 276 (61%). Episodic maintenance therapy was successful in 19 of 40 patients (48%). Estimated 5-year sustained benefit was 55.7% (95% confidence interval, 48.8-62.6). Concomitant thiopurines were associated with improved sustained benefit. A second course of infliximab after previous discontinuation was prescribed in 131 patients with similar efficacy rates. Abdominal surgical intervention rate per 100 patient-years was significantly reduced after infliximab initiation in patients with a scheduled maintenance regime (reduction, 2.70; 95% confidence interval, -4.82 to -0.35; P = 0.018). Mortality and malignancy rates were 1.9% (0.39/100 patient-years) and 3.4% (0.70/100 patient-years), respectively. CONCLUSIONS: The present study shows an estimated 5-year sustained benefit of 55.7% in patients with Crohn's disease treated with infliximab maintenance therapy. Remission induction and maintenance were equally successful in patients starting infliximab and patients who temporarily stopped and were retreated. Long-term use of infliximab was safe and reduced the need for surgery in patients on scheduled maintenance therapy.

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