201 results on '"Buskens CJ"'
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2. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations
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Gionchetti, P, Dignass, A, Danese, S, Dias, FJM, Rogler, G, Lakatos, PL, Adamina, M, Ardizzone, S, Buskens, CJ, Sebastian, S, Laureti, S, Sampietro, GM, Vucelic, B, van der Woude, C.J., Barreiro-de Acosta, M, Maaser, C, Portela, F, Vavricka, S R, Gomollon, F, Ecco, Gastroenterology & Hepatology, Gionchetti, Paolo, Dignass, Axel, Danese, Silvio, Magro Dias, Fernando José, Rogler, Gerhard, Lakatos, Péter Laszlo, Adamina, Michel, Ardizzone, Sandro, Buskens, Christianne J, Sebastian, Shaji, Laureti, Silvio, Sampietro, Gianluca M, Vucelic, Bori, van der Woude, C Janneke, Barreiro-de Acosta, Manuel, Maaser, Christian, Portela, Francisco, Vavricka, Stephan R, Gomollón, Fernando, University of Zurich, Gionchetti, P, Dignass, A, Danese, S, Dias, Fjm, Rogler, G, Lakatos, Pl, Adamina, M, Ardizzone, S, Buskens, Cj, Sebastian, S, Laureti, S, Sampietro, Gm, Vucelic, B, van der Woude, Cj, Barreiro-de Acosta, M, Maaser, C, Portela, F, Vavricka, Sr, Gomollon, F, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Surgery
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Budesonide ,Crohn’s disease ,medicine.medical_specialty ,Evidence-based practice ,budesonide ,immunosuppressant ,610 Medicine & health ,Disease ,Biologics ,Investigations ,Management of Crohn's disease ,Gastroenterology ,Anti-integrins ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,thiopurine ,Diagnosis ,medicine ,2715 Gastroenterology ,Colitis ,Intensive care medicine ,Anti-TNFs ,Immunosuppressant ,Crohn's disease ,Thiopurine ,Thiopurine methyltransferase ,biology ,investigation ,treatment ,business.industry ,steroid ,General Medicine ,anti-TNF ,medicine.disease ,Treatment ,diagnosi ,10219 Clinic for Gastroenterology and Hepatology ,anti-integrin ,030220 oncology & carcinogenesis ,biology.protein ,Steroids ,030211 gastroenterology & hepatology ,business ,biologic ,medicine.drug - Abstract
This paper is the second in a series of two publications relating to the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn’s disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al. JCC 2016].
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- 2017
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3. Risk factors for proximal disease extension and colectomy in left‐sided ulcerative colitis
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Sahami, S, primary, Konté, K, additional, Buskens, CJ, additional, Tanis, PJ, additional, Löwenberg, M, additional, Ponsioen, CJ, additional, Brink, GR, additional, Bemelman, WA, additional, and D’Haens, GR, additional
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- 2017
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4. Erratum to: Multicentre randomized controlled trial comparing ferric(III) carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients
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Borstlap, WAA, Buskens, CJ, Tytgat, KMAJ, Tuynman, JB, Consten, ECJ, Tolboom, RC, Heuff, G., van Geloven, AAW, van Wagensveld, BA, Wientjes, CACA, Gerhards, MF, de Castro, SMM, Jansen, J., van der Ven, AWH, van der Zaag, E., Omloo, JM, van Westreenen, HL, Winter, DC, Kennelly, RP, Dijkgraaf, MGW, Tanis, PJ, and Bemelman, WA
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Surgery ,General Medicine - Published
- 2015
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5. Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis: a multicentre, parallel-group, randomised, open-label trial
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Vennix, S, Musters, Gd, Mulder, Im, Swank, Ha, Consten, Ec, Belgers, Eh, van Geloven AA, Gerhards, Mf, Govaert, Mj, van Grevenstein WM, Hoofwijk, Ag, Kruyt, Pm, Nienhuijs, Sw, Boermeester, Ma, Vermeulen, J, van Dieren, S, Lange, Jf, Bemelman, Wa, Collaborators (138) Hop WC, Ladies trial colloborators., Opmeer, Bc, Reitsma, Jb, Scholte, Ra, Waltmann, Ew, Legemate, Da, Bartelsman, Jf, Meijer, Dw, de Brouwer, M, van Dalen, J, Durbridge, M, Geerdink, M, Ilbrink, Gj, Mehmedovic, S, Middelhoek, P, Boom, Mj, van der Bilt JD, van Olden GD, Stam, Ma, Verweij, Ms, Busch, Or, Buskens, Cj, El-Massoudi, Y, Kluit, Ab, van Rossem CC, Schijven, Mp, Tanis, Pj, Unlu, C, Karsten, Tm, de Nes LC, Rijna, H, van Wagensveld BA, Koffeman, Gi, Steller, Ep, Tuynman, Jb, Bruin, Sc, van der Peet DL, Blanken-Peeters, Cf, Cense, Ha, Jutte, E, Crolla, Rm, van der Schelling GP, van Zeeland, M, de Graaf EJ, Groenendijk, Rp, Vermaas, M, Schouten, O, de Vries MR, Prins, Ha, Lips, Dj, Bosker, Rj, van der Hoeven JA, Diks, J, Plaisier, Pw, Sietses, C, Stommel, Mw, de Hingh IH, Luyer, Md, van Montfort, G, Ponten, Eh, Smulders, Jf, van Duyn EB, Klaase, Jm, Swank, Dj, Ottow, Rt, Stockmann, Hb, Vuylsteke, Jc, Belgers, Hj, Fransen, S, von Meijenfeldt EM, Sosef, Mn, Hendriks, Er, ter Horst, B, Leeuwenburgh, Mm, van Ruler, O, Vogten, Jm, Vriens, Ej, Westerterp, M, Eijsbouts, Qa, Bentohami, A, Bijlsma, Ts, de Korte, N, Nio, D, Joosten, Jj, Tollenaar, Ra, Stassen, Lp, Wiezer, Mj, Hazebroek, Ej, Smits, Ab, van Westreenen HL, Brandt, A, Nijboer, Wn, Toorenvliet, Br, Weidema, Wf, Coene, Pp, Mannaerts, Gh, den Hartog, D, de Vos RJ, Zengerink, Jf, Hulsewé, Kw, Melenhorst, J, Stoot, Jh, Steup, Wh, Huijstee, Pj, Merkus, Jw, Wever, Jj, Maring, Jk, Heisterkamp, J, Vriens, Mr, Besselink, Mg, Borel Rinkes IH, Witkamp, Aj, Slooter, Gd, Konsten, Jl, Engel, Af, Pierik, Eg, Frakking, Tg, van Geldere, D, Patijn, Ga, D'Hoore, Aj, de Buck van Overstraeten, A, Miserez, M, Terrasson, I, Wolthuis, A, Di Saverio, S, De Blasiis, Mg., Surgery, Immunology, Other departments, AII - Amsterdam institute for Infection and Immunity, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Amsterdam Public Health, Clinical Research Unit, ACS - Amsterdam Cardiovascular Sciences, 02 Surgical specialisms, Gastroenterology and Hepatology, Graduate School, and CCA -Cancer Center Amsterdam
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Male ,medicine.medical_specialty ,Colon ,Sigmoid ,Peritonitis ,Research Support ,law.invention ,Diverticulitis, Colonic ,Stoma ,Colonic ,Sigmoidectomy ,Randomized controlled trial ,law ,Colon, Sigmoid ,Journal Article ,medicine ,Clinical endpoint ,Humans ,Comparative Study ,Peritoneal Lavage ,Non-U.S. Gov't ,Laparoscopy ,Diverticulitis ,medicine.diagnostic_test ,business.industry ,Research Support, Non-U.S. Gov't ,Sigmoidoscopy ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Multicenter Study ,Treatment Outcome ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,Intestinal Perforation ,Randomized Controlled Trial ,Female ,business - Abstract
Item does not contain fulltext BACKGROUND: Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. METHODS: We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (>/=20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age [/=60 years]) using secure online computer randomisation to laparoscopic lavage, Hartmann's procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1.28, 95% CI 0.54-3.03, p=0.58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0.43). INTERPRETATION: Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. FUNDING: Netherlands Organisation for Health Research and Development.
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- 2015
6. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial
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Klaver, CEL, Musters, GD, Bemelman, WA, Punt, CJA, Verwaal, VJ, Dijkgraaf, MGW, Aalbers, AGJ (Arend), van der Bilt, JDW, Boerma, D, Bremers, AJA, Burger, Pim, Buskens, CJ, Evers, P, van Ginkel, RJ, Grevenstein, WMU, Hemmer, PHJ, de Hingh, IHJT, Lammers, LA, van Leeuwen, BL, Meijerink, WJHJ, Nienhuijs, SW, Pon, J, Radema, SA, van Ramshorst, B, Snaebjornsson, P, Tuynman, JB, te Velde, EA, Wiezer, MJ, de Wilt, JHW (Johannes), Tanis, PJ, Klaver, CEL, Musters, GD, Bemelman, WA, Punt, CJA, Verwaal, VJ, Dijkgraaf, MGW, Aalbers, AGJ (Arend), van der Bilt, JDW, Boerma, D, Bremers, AJA, Burger, Pim, Buskens, CJ, Evers, P, van Ginkel, RJ, Grevenstein, WMU, Hemmer, PHJ, de Hingh, IHJT, Lammers, LA, van Leeuwen, BL, Meijerink, WJHJ, Nienhuijs, SW, Pon, J, Radema, SA, van Ramshorst, B, Snaebjornsson, P, Tuynman, JB, te Velde, EA, Wiezer, MJ, de Wilt, JHW (Johannes), and Tanis, PJ
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Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 degrees C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 1
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- 2015
7. Local Application of Gentamicin in the Prophylaxis of Perineal Wound Infection After Abdominoperineal Resection: A Systematic Review
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Musters, GD, Burger, Pim, Buskens, CJ, Bemelman, WA, Tanis, PJ, Musters, GD, Burger, Pim, Buskens, CJ, Bemelman, WA, and Tanis, PJ
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Use of topical antibiotics to improve perineal wound healing after abdominoperineal resection (APR) is controversial. The aim of this systematic review was to determine the impact of local application of gentamicin on perineal wound healing after APR. The electronic databases Pubmed, EMBASE, and Cochrane library were searched in January 2015. Perineal wound outcome was categorized as infectious complications, non-infectious complications, and primary perineal wound healing. From a total of 582 articles, eight studies published between 1988 and 2012 were included: four randomized controlled trials (RCTs), three comparative cohort studies, and one cohort study without control group. Gentamicin was administered using sponges (n = 3), beads (n = 4), and by local injection (n = 1). There was substantial heterogeneity regarding underlying disease, definition of outcome parameters and timing of perineal wound evaluation among the included studies, which precluded meta-analysis with pooling. Regarding infectious complications, three of six evaluable studies demonstrated a positive effect of local application of gentamicin: one of four RCTs and both comparative cohort studies. Only two RCTs reported on non-infectious complications, showing no significant impact of gentamicin sponge. All three comparative cohort studies demonstrated a significantly higher percentage of primary perineal wound healing after local application of gentamicin beads, but only one out of three evaluable RCTs did show a positive effect of gentamicin sponges. Currently available evidence does not support perineal gentamicin application after APR.
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- 2015
8. Hospital volume and hospital mortality for esophagectomy
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van Lanschot, JJB, Hulscher, JBF, Buskens, CJ, Tilanus, Hugo, ten Kate, FJW, Obertop, H, Surgery, and Pathology
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- 2001
9. Neoadjuvant selective COX-2 inhibition downregulates important oncogenic pathways in patients with esophageal adenocarcinoma
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Tuynman, JB, primary, Buskens, CJ, additional, Kemper, K, additional, ten Kate, FJW, additional, Offerhaus, GJA, additional, Richel, DJ, additional, and van Lanschot, JJB, additional
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- 2006
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10. Decreased incidence of isolated tumor cells in lymph nodes after laparoscopic resection for colorectal cancer.
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van der Zaag ES, Buskens CJ, Vlug MS, Peters HM, Bouma WH, Bemelman WA, van der Zaag, E S, Buskens, C J, Vlug, M S, Peters, H M, Bouma, W H, and Bemelman, W A
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Background: Laparoscopic surgery has potential for less tumor cell spread because of the no-touch technique. We assessed the effect of the surgical approach (open versus no-touch laparoscopic) on the presence of tumor cells in sentinel lymph nodes (SN) of patients with stage I and II colorectal cancer.Methods: A single-center consecutive prospective series of patients operated on for colorectal cancer was analyzed. After conventional hematoxylin and eosin (H&E) staining, 107 patients without lymphatic metastases were included; 59 patients had open surgery, and 48 patients underwent laparoscopic resection. Patients in the laparoscopic group underwent a no-touch medial to lateral approach, whereas the conventional lateral to medial approach was applied in open surgery. A SN procedure was performed in all patients. The SNs were immunohistochemically analyzed for presence of occult tumor cells (OTC). According to the American Joint Committee on Cancer (AJCC) these tumor cells were divided into micrometastases (0.2-2 mm) or isolated tumor cells (ITC, < 0.2 mm).Results: In ten patients micrometastases were found, equally distributed between the two groups. However, ITC were more often found after open surgery (18 versus 5 patients, p = 0.03). Presence of OTC was related to depth of tumor invasion and tumor diameter > 3.5 cm. Logistic regression analysis identified lymphovascular invasion as a predictor for micrometastases [odds ratio (OR) 18.4], whereas open resection was predictive for presence of ITC (OR 3.3).Conclusions: No-touch medial to lateral laparoscopic surgery results in less isolated tumor cells in lymph nodes compared with open lateral to medial surgery in patients with stage I and II colorectal cancer. [ABSTRACT FROM AUTHOR]- Published
- 2011
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11. Treatment of Perianal Fistulas in Crohn's Disease, Seton Versus Anti-TNF Versus Surgical Closure Following Anti-TNF [PISA]: A Randomised Controlled Trial
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Apollo Pronk, Merel E. Stellingwerf, Karlien F. Bruin, Antonino Spinelli, Silvio Danese, David D. E. Zimmerman, Sebastiaan A.C. van Tuyl, Marcel G. W. Dijkgraaf, Cyriel Y. Ponsioen, Geert R. D'Haens, Jarmila D. W. van der Bilt, Karin A. T. G. M. Wasmann, Christianne J. Buskens, Krisztina B Gecse, E. Joline de Groof, Michael F. Gerhards, Willem A Bemelman, M.W. Mundt, Jeroen M. Jansen, Graduate School, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Epidemiology and Data Science, APH - Methodology, Wasmann, Katgm, de Groof, Ej, Stellingwerf, Me, D'Haens, Gr, Ponsioen, Cy, Gecse, Kb, Dijkgraaf, Mgw, Gerhards, Mf, Jansen, Jm, Pronk, A, van Tuyl, Sac, Zimmerman, Dde, Bruin, Kf, Spinelli, A, Danese, S, van der Bilt, Jdw, Mundt, Mw, Bemelman, Wa, and Buskens, Cj
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Male ,Crohn’s disease ,Fistula ,Perianal fistula ,law.invention ,Anti-TNF ,Primary outcome ,0302 clinical medicine ,Crohn Disease ,Quality of life ,Randomized controlled trial ,law ,Data monitoring committee ,Crohn's disease ,Medical treatment ,Gastroenterology ,General Medicine ,Combined Modality Therapy ,Outcome and Process Assessment, Health Care ,030220 oncology & carcinogenesis ,Early Termination of Clinical Trials ,Cohort ,Drainage ,Female ,030211 gastroenterology & hepatology ,Medical Futility ,Adult ,Reoperation ,medicine.medical_specialty ,Randomization ,03 medical and health sciences ,medicine ,Humans ,Rectal Fistula ,Trial registration ,AcademicSubjects/MED00260 ,Wound Closure Techniques ,business.industry ,General surgery ,Adalimumab ,Patient Acuity ,Consolidated Standards of Reporting Trials ,Original Articles ,medicine.disease ,Infliximab ,Surgery ,Clinical trial ,Good clinical practice ,Quality of Life ,Tumor Necrosis Factor Inhibitors ,business - Abstract
Background: Most patients with perianal Crohn's disease fistulas receive medical treatment with anti-TNF. So far, outcomes of anti-TNF have not been directly compared to chronic seton drainage or surgical closure. We hypothesized that chronic seton drainage would result in fewer re-interventions compared to anti-TNF and surgical closure. Methods: This multicentre, randomised trial was performed in 19 European centres. Patients with high perianal Crohn's fistulas with a single internal opening were randomly assigned in a 1:1:1 ratio to chronic seton drainage, long-term anti-TNF therapy, or surgical closure using a central web-based system without stratification. Patients were analysed according to the intention-to-treat principle. The primary outcome was the cumulative number of patients with fistula-related re-intervention(s) at 1.5 year. Patients refusing randomisation due to a specific treatment preference were included in a parallel prospective PISA registry cohort. Findings: Between September 14, 2013 and November 20, 2017, 44 of the 126 planned patients were randomised. The study was stopped by the data safety monitoring board because of futility. Seton treatment was associated with the highest re-intervention rate (10/15, versus 6/15 anti-TNF and 3/14 surgical closure patients, P = 0·02). No substantial differences in perianal disease activity and quality of life between the three treatment groups were observed. Interestingly, in the PISA prospective registry (n = 50), inferiority of chronic seton treatment was not observed for any outcome measure. Interpretation: The results imply that chronic seton treatment should not be recommended as the sole or superior treatment for perianal Crohn's fistulas. However, the statistical inferiority of seton treatment should be interpreted with caution, due to the crucial aspects of small numbers and as this inferiority could not be confirmed in the PISA registry data. Trial Registration Number: The trial is registered with the Dutch Trialregister.nl number NTR4137. Funding Statement: The Netherlands Organization for Health Research and Development and the Crohn and Colitis Foundation. Declaration of Interests: KAW, EJdG, MES, MGD, MFG, JMJ, AP, SAvT, DDZ, KFB, JvdB, MWM, WAB, and CJB have no conflicts of interests to declare. GRD’H has served as advisor for Abbvie, Ablynx, Allergan, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Echo Pharmaceuticals, Eli Lilly, Engene, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, Prometheus laboratories/Nestle, Progenity, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts and Vifor. CYP has served as adviser for Abbvie, Takeda, and Pliant, declares a grant from Takeda, and received speaker’s fees from Abbvie, Tillotts, and Takeda. KBG has served as speaker and/or advisor for Amgen, AbbVie, Biogen, Boehringer Ingelheim, Ferring, Hospira, MSD, Pfizer, Samsung Bioepis, Sandoz, Takeda and Tigenix. AS has served as speaker and/or advisor for Takeda. SD has served as a speaker, a consultant and an advisory board member for Abbvie, Ferring, Hospira, Johnson & Johnson, Merck, Millennium Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma, and Vifor. Ethics Approval Statement: The study was performed in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines, and is reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. The trial received central approval from the medical ethics committee at the Amsterdam UMC, location AMC, and from the corresponding committees in all participating centres.
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- 2020
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12. Improving Enhanced Recovery after Surgery (ERAS): The Effect of a Patient-Centred Mobile Application and an Activity Tracker on Patient Engagement in Colorectal Surgery.
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van der Storm SL, Jansen M, Mulder MD, Marsman HA, Consten ECJ, den Boer FC, de Boer HD, Bemelman WA, Buskens CJ, and Schijven MP
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Background: The Enhanced Recovery After Surgery (ERAS) protocol improved perioperative colorectal care. Although the protocol is firmly implemented across hospital settings, there are benefits to gain by actively involving patients in their recovery. The main objective of this study was to investigate whether compliance with selected items in the ERAS protocol could further improve by using a patient-centred mobile application., Method: This multicentre, randomised controlled trial was conducted between October 2019 and September 2022. Patients aged 18 years or older who underwent elective colorectal surgery, and in possession of a smartphone were included. The intervention group used a mobile application combined with an activity tracker to be guided and supported through the ERAS pathway. The control group received standard care and wore an activity tracker to monitor their daily activities. The primary outcome was overall compliance with selected active elements of the ERAS protocol., Results: In total, 140 participants were randomised to either the intervention (n = 72) or control group (n = 68). The use of the ERAS App demonstrated a significant improvement in overall compliance by 10%, particularly in early solid food intake by 42% and early mobilization by 27%. Postoperative or patient reported outcomes did not differ between groups., Conclusion: The smartphone application 'ERAS App' is able to improve adherence to the active elements of the ERAS protocol for colorectal surgery. This is an important step towards optimizing perioperative care for colorectal surgery patients and enabling patients to optimize being in control of their own recovery. Trial registration: ERAS APPtimize, NTR7314 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON29410)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Sebastiaan van der Storm, Malou Mulder, Hendrik Marsman, Frank den Boer, have no conflicts of interest to disclose. Marilou Jansen is the content developer of the app and Marlies Schijven is the owner of the app. Esther Consten is Proctor for Intuitive Surgical. Willem Bemelman declares that he has received scientific grants from VIFOR and has received speaker fees from Janssen, Medtronic and Galapagos. Christianne Buskens declares that she has received scientific grants from Boehringer Ingelheim and Roche and has received speaker fees from Janssen, Medtronic and Galapagos Hans de Boer is Chairman ERAS Society and Chairman Dutch ERAS Society.
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- 2024
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13. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.
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Adamina M, Minozzi S, Warusavitarne J, Buskens CJ, Chaparro M, Verstockt B, Kopylov U, Yanai H, Vavricka SR, Sigall-Boneh R, Sica GS, Reenaers C, Peros G, Papamichael K, Noor N, Moran GW, Maaser C, Luglio G, Kotze PG, Kobayashi T, Karmiris K, Kapizioni C, Iqbal N, Iacucci M, Holubar S, Hanzel J, Sabino JG, Gisbert JP, Fiorino G, Fidalgo C, Ellu P, El-Hussuna A, de Groof J, Czuber-Dochan W, Casanova MJ, Burisch J, Brown SR, Bislenghi G, Bettenworth D, Battat R, Atreya R, Allocca M, Agrawal M, Raine T, Gordon H, and Myrelid P
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- Humans, Preoperative Care methods, Preoperative Care standards, Immunosuppressive Agents therapeutic use, Crohn Disease surgery, Crohn Disease drug therapy
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This article is the second in a series of two publications on 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 prior ECCO Guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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14. Tuft cells act as regenerative stem cells in the human intestine.
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Huang L, Bernink JH, Giladi A, Krueger D, van Son GJF, Geurts MH, Busslinger G, Lin L, Begthel H, Zandvliet M, Buskens CJ, Bemelman WA, López-Iglesias C, Peters PJ, and Clevers H
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- Adult, Animals, Humans, Mice, Cell Proliferation, Cell Survival radiation effects, Epithelial Cells cytology, Epithelial Cells metabolism, Epithelial Cells radiation effects, Fetus cytology, Interleukin-13 metabolism, Interleukin-13 pharmacology, Interleukin-4 metabolism, Interleukin-4 pharmacology, Intestinal Mucosa cytology, Intestinal Mucosa radiation effects, Organoids cytology, Organoids radiation effects, Wnt Proteins metabolism, Intestines cytology, Intestines radiation effects, Regeneration radiation effects, Stem Cells cytology, Stem Cells radiation effects, Stem Cells metabolism, Tuft Cells classification, Tuft Cells cytology, Tuft Cells metabolism, Tuft Cells radiation effects
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In mice, intestinal tuft cells have been described as a long-lived, postmitotic cell type. Two distinct subsets have been identified: tuft-1 and tuft-2 (ref.
1 ). By combining analysis of primary human intestinal resection material and intestinal organoids, we identify four distinct human tuft cell states, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that tuft cell numbers rapidly increase on interleukin-4 (IL-4) and IL-13 exposure, as reported previously in mice2-4 . This occurs through proliferation of pre-existing tuft cells, rather than through increased de novo generation from stem cells. Indeed, proliferative tuft cells occur in vivo both in fetal and in adult human intestine. Single mature proliferating tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans., (© 2024. The Author(s).)- Published
- 2024
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15. Prolonged time to diagnosis of Crohn's disease in patients with perianal fistulas negatively affects long-term outcomes.
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Munster LJ, Pronk AJM, Mundt MW, Hompes R, Bemelman WA, van der Bilt JDW, and Buskens CJ
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Background and Aim: This study aims to evaluate the effect of time to Crohn's disease (CD) diagnosis on perianal fistula (PAF) outcomes in patients with a fistula as first manifesting sign., Methods: In this multicenter, retrospective study, CD patients with a PAF preceding CD diagnosis between November 2015 and June 2022 were included. The primary outcome parameter was the time to CD diagnosis and its correlation with long-term outcomes., Results: In total, 126 patients with a PAF prior to CD diagnosis were identified. Median time to CD diagnosis was 15.0 months (IQR 3.8-47.3). A total of 49 patients (38.9%) had a clinically closed fistula of which 21 patients (42.9%) achieved radiological healing. 25 patients (19.8%) underwent defunctioning, of which 9 patients (36.0%) needed proctectomy. Median time to CD diagnosis was shortest in patients with radiological healing (4.0 months, IQR 2.0-16.5) or clinical closure without radiological healing (11.0 months, IQR 3.0-47.8). In patients without fistula closure (n=51), median time to CD diagnosis was significantly longer compared to patients with fistula closure, 18.0 months vs 8.0 months (p=0.031). In patients who needed defunctioning, median time to diagnosis was more than twice as long compared to patients without defunctioning, 30.0 months vs 12.0 months (p=0.054)., Conclusion: A prolonged time to CD diagnosis in patients with a PAF as a manifesting sign is associated with worse long-term outcomes. Patients in whom radiological healing could be achieved had the shortest time to CD diagnosis, emphasizing the relevance of increased clinical awareness of underlying CD in fistula patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
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- 2024
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16. Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial.
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van der Does de Willebois EML, Bellato V, Duijvestein M, van der Bilt JDW, van Dongen K, Spinelli A, D'Haens GR, Mundt MW, Furfaro F, Danese S, Vignali A, Bemelman WA, and Buskens CJ
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- Humans, Male, Female, Adult, Middle Aged, Treatment Outcome, Anastomosis, Surgical methods, Anastomosis, Surgical adverse effects, Colectomy methods, Colectomy adverse effects, Crohn Disease surgery, Crohn Disease pathology, Mesentery surgery, Mesentery pathology, Ileum surgery, Ileum pathology, Recurrence, Colon surgery, Colon pathology, Colon diagnostic imaging
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Background: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection., Methods: This international, randomised controlled trial was done in six hospitals and tertiary care centres in the Netherlands and Italy. Eligible patients were aged 16 years or older and had Crohn's disease that was previously confirmed by endoscopy in the terminal ileum or ileocolic region (L1 or L3 disease), with an imaging update in the past 3 months (ultrasound, MRI, or CT enterography). Eligible patients were scheduled to undergo primary ileocolic resection with ileocolic anastomosis. Enrolled patients were assigned by use of simple random allocation (1:1) to either extended mesenteric resection (intervention) or conventional mesenteric sparing resection (control). The primary endpoint was endoscopic recurrence 6 months after surgery. Analyses were done in all patients with primary endpoint data, excluding those who had no anastomosis, a postoperative diagnosis other than Crohn's disease, or withdrew consent. This trial was registered with ClinicalTrials.gov, NCT04538638., Findings: Between Feb 19, 2020, and April 24, 2023, we assessed 217 patients for eligibility. 78 patients were excluded due to failure to meet the inclusion criteria or refusal to participate. 139 patients were enrolled and randomly assigned to either extended mesenteric resection (n=71) or mesenteric sparing resection (n=68). All 139 patients underwent surgery. Six patients were excluded after random assignment due to withdrawal of consent (n=2), postoperative diagnosis other than Crohn's disease (n=2) and no anastomosis performed (in case of a stoma; n=2). Two patients were lost to follow-up, and two more patients deviated from the protocol by undergoing investigations other than endoscopy 6 months after. 133 patients were included in the baseline analysis (67 in the extended resection group and 66 in the sparing resection group) of whom 57 (43%) were male. Baseline characteristics were similar between the groups, and median patient age was 36 years (IQR 25-54). 131 patients were analysed for the primary outcome. There was no difference between groups in the rate of endoscopic recurrence at 6 months after surgery (28 [42%] of 66 patients in the extended mesenteric resection group vs 28 [43%] of 65 patients in the mesenteric sparing resection group, relative risk 0·985, 95% CI 0·663-1·464; p=1·0). Five (8%) of 66 patients in the extended mesenteric resection group had anastomotic leakage within the 30 days after surgery, as did one (2%) of 65 in the mesenteric sparing group. Postoperative complications of Clavien-Dindo grade IIIa or higher were reported in seven (11%) patients in the mesenteric resection group and five (8%) in the mesenteric sparing group., Interpretation: Extended mesenteric resection was not superior to conventional resection with regard to endoscopic Crohn's disease recurrence. These data support the guideline-recommended mesenteric sparing approach., Funding: Topconsortia voor Kennis en Innovatie-Topsector Life Sciences & Health., Competing Interests: Declaration of interests MD received speaking fees from Bristol Meyers Squibb, Takeda, and Galapagos; served in an advisory board for AbbVie, Bristol Meyers Squibb, Celltrion, Galapagos, Janssen, and Takeda; and received grant or research support from Pfizer, Bristol Meyers Squibb, Galapagos, and Janssen. AS acted as a consultant or speaker for Johnson and Johnson, Striker, and Oasis. FF received consultant fees from AbbVie and MSD and has served for speaker for Janssen and Pfizer. GRD has served as an advisor or speaker for AbbVie, Alimentiv, Amgen, Biora, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Ferring, Eli Lilly, enGene, Galapagos, Glaxo Smith Kline, Immunic, Index Pharmaceuticals, Johnson and Johnson, Landos, Lument, Mitsubishi Pharma, Polpharma, Prometheus Biosciences, Prometheus Laboratories, Procise Diagnostics, Protagonist, Sandoz, Setpoint, Takeda, Tillotts, and Ventyx. SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB, Vial, and Vifor and reports lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer, and Takeda. CJB reports an unrestricted research grant from Boehringer Ingelheim, and Roche; received speaker's fees from Takeda, AbbVie, Janssen, MSD, and Tillots Pharma; and is part of the advisory board of Takeda. VB declares to have received support for attending a conference from THD. WAB has received research funding from VIFOR and is a consultant for Braun. The other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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17. External validation of the MAGNIFI-CD index in patients with complex perianal fistulising Crohn's disease.
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Beek KJ, Mulders LGM, van Rijn KL, Horsthuis K, Tielbeek JAW, Buskens CJ, D'Haens GR, Gecse KB, and Stoker J
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Background: There is an increasing need for objective treatment monitoring in perianal fistulising Crohn's disease (pfCD). Therefore, the magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD) index has been designed and internally validated on the ADMIRE-CD trial cohort. The aim of this study was to externally validate the MAGNIFI-CD index to monitor response to medical and surgical treatment regimens in pfCD., Methods: A retrospective longitudinal cohort was established of consecutive patients with complex pfCD treated with surgical and/or medical therapy and a baseline and follow-up MRI between January 2007 and May 2021. The MAGNIFI-CD index was scored by two independent, abdominal radiologists blinded for time points and clinical outcomes. Responsiveness, reliability, and test accuracy regarding clinically important improvement were assessed. Cut-offs for response and remission were selected classified on fistula drainage assessment and physician global assessment., Results: A total of 65 patients (51% female, median age 32 years) were included. A clinically relevant responsiveness of the MAGNIFI-CD was shown, with a significant decrease in clinical remitters and responders with a median MAGNIFI-CD of 18.0 [7.5-20.0] to 9.0 [0.8-16.0] (p < 0.001) and non-significant change in non-responders with a median MAGNIFI-CD of 20.0 [12.0-23.0] to 18.0 [13.0-21.0] (p = 0.22). There was an 'almost perfect' interobserver agreement (ICC = 0.87; 95% CI 0.80-0.92) for the MAGNIFI-CD index. An optimal cut-off value was defined as a decrease of 2 points for clinical response, and a MAGNIFI-CD ≤ 6 for remission at follow-up MRI., Conclusion: The MAGNIFI-CD index is a responsive and reliable MRI scoring instrument for treatment monitoring in perianal fistulising Crohn's disease., Clinical Relevance Statement: The MAGNIFI-CD index is a well-structured, responsive scoring instrument to assess fistula severity and activity that allows quantitative detection of changes in therapy response in patients with perianal fistulising Crohn's disease, thereby facilitating endpoints in clinical trials., Key Points: Well-defined cut-offs for response and remission are needed for objective treatment monitoring of perianal fistulising Crohn's disease (pfCD). Cut-off values for remission and for response at 6 months follow-up were defined. Interobserver agreement was good. The MAGNIFI-CD index is responsive and reliable for treatment monitoring and is suitable for use in clinical trials., (© 2024. The Author(s).)
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- 2024
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18. Fistulizing Perianal Disease as a First Manifestation of Crohn's Disease: A Systematic Review and Meta-Analysis.
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Munster LJ, Mönnink GLE, van Dieren S, Mundt MW, D'Haens GRAM, Bemelman WA, Buskens CJ, and van der Bilt JDW
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Background : Incidences of perianal fistulas (PAFs) as a first manifestation of Crohn's disease (CD) vary widely in the literature. Aim: To analyse the percentage of patients with a PAF preceding CD diagnosis and assess the time to diagnosis. Methods : A systematic literature search was conducted. Studies reporting on patients with a PAF preceding CD diagnosis were identified. Primary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD and their time to CD diagnosis. Secondary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD diagnosis in predefined patient subgroups, including (1) sex (men vs. women), (2) ethnicity (Asian vs. non-Asian), and (3) age (paediatric (0-18 y) and patients with elderly onset CD (>60 y) vs. adult patients (18-60 y)). Results : Seventeen studies were included (34,030 patients with CD). In the overall CD population, a PAF preceded CD in 8.6% [95%CI; 5.72; 12.71] with a weighted mean time to CD diagnosis of 45.9 (31.3) months. No studies reported details on sex differences in patients with a PAF as a manifesting sign of CD. In Asian populations, a PAF preceded CD in 17.66% [95%CI; 11.45; 26.25], which was significantly higher when compared with non-Asians (4.99% [95%CI; 3.75; 6.60], OR:3.99, p < 0.0001). In adolescents, an incidence of 9.17% [95%CI; 5.92; 13.93] was found with significantly lower incidences in paediatric patients (6.38% [95%CI; 1.84; 19.85], OR:0.53, p < 0.0001), and elderly-onset patients (3.77% [95%CI; 1.68; 8.25], OR:0.44, p = 0.0035). Conclusions : This systematic review shows that in the literature, almost 10% of patients present with a PAF as a first manifestation of CD, with a mean time to diagnosis of almost four years. These results emphasise that increased clinical awareness is needed.
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- 2024
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19. Perianal Fistulizing Crohn's Disease: Utilizing the TOpClass Classification in Clinical Practice to Provide Targeted Individualized Care.
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Hanna LN, Anandabaskaran S, Iqbal N, Geldof J, LeBlanc JF, Dige A, Lundby L, Vermeire S, D'Hoore A, Verstockt B, Bislenghi G, De Looze D, Lobaton T, Van de Putte D, Spinelli A, Carvello M, Danese S, Buskens CJ, Gecse K, Hompes R, Becker M, van der Bilt J, Bemelman W, Sebastian S, Moran G, Lightner AL, Wong SY, Colombel JF, Cohen BL, Holubar S, Ding NS, Behrenbruch C, Sahnan K, Misra R, Lung P, Hart A, and Tozer P
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Background & Aims: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice., Methods: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia., Results: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group., Conclusion: This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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20. Mesenchymal stem cell therapy for therapy refractory complex Crohn's perianal fistulas: a case series.
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Pronk AJM, Beek KJ, Wildenberg ME, Bemelman WA, Stoker J, and Buskens CJ
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- Humans, Male, Female, Adult, Middle Aged, Magnetic Resonance Imaging, Treatment Outcome, Crohn Disease therapy, Mesenchymal Stem Cell Transplantation methods, Rectal Fistula therapy
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Background: Mesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for Crohn's perianal fistulas. It has been demonstrated that a fibrotic tract on MRI with a MAGNIFI-CD score ≤ 6 is the best predictor for long-term clinical closure. Therefore, the aim of the current study was to analyse the effectiveness of MST for complex Crohn's perianal fistulas based on MRI., Methods: Consecutive patients with complex Crohn's perianal fistulas, previously failing both anti-TNF treatment and surgical closure, who had surgical closure of the internal opening with MST were included. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD ≤ 6 on MRI, read by an experienced radiologist., Results: Between December 2019 and March 2023, 30 patients (15 males) with 48 fistula tracts were included with a median follow-up of 16.5 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0-6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0-20.0) which significantly decreased to 8.0 (IQR 3.0-15.0) after treatment (p = 0.001). Clinical closure was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU, all with clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0-14.0) to 4.0 (IQR 0.0-7.3) (p = 0.001)., Conclusion: MST is a promising treatment strategy for therapy refractory Crohn's perianal fistulas, resulting in > 40% radiological remission, clinical closure in 70% and a significant improvement in quality of life. No recurrences were seen in patients with radiological remission., (© 2024. The Author(s).)
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- 2024
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21. The Clinical Relevance of an Inflamed Appendix in Crohn's Disease.
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van der Does de Willebois EML, Sari C, Mookhoek A, Joustra V, van Dieren S, D'Haens GR, Bemelman WA, and Buskens CJ
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- Humans, Female, Male, Adult, Appendicitis surgery, Appendicitis complications, Appendix pathology, Appendix surgery, Ileum surgery, Ileum pathology, Prognosis, Retrospective Studies, Young Adult, Clinical Relevance, Crohn Disease surgery, Crohn Disease complications, Crohn Disease pathology, Appendectomy methods, Recurrence
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Background and Aims: An appendectomy for appendiceal inflammation has been suggested to ameliorate the clinical course of patients with ulcerative colitis [UC]. In contrast, for Crohn's disease [CD] an inverse association has been suggested with a higher incidence of CD and worse prognosis after appendectomy. The aim of this study was to analyse the clinical relevance of an inflamed appendix in CD patients undergoing ileocaecal resection [ICR]., Methods: All consecutive patients undergoing primary ICR between 2007 and 2018 were considered for inclusion. Microscopic data of available appendiceal resection specimens [n = 99] were revised by a dedicated inflammatory bowel disease [IBD] pathologist and scored as inflamed or not inflamed. Eighteen patients had a previous appendectomy. Pathological findings were correlated with disease characteristics and recurrence rates [clinical, endoscopic, and intervention-related]., Results: In total 117 patients were included, 77 [65.8%] females, with a median age of 30 years (interquartile range [IQR] 24-43), and a median follow up of 102 months [IQR 76-114]. Of patients without previous appendectomy [n = 99], 39% had an inflamed appendix. No significant differences in disease characteristics [eg, disease location, behaviour, time to surgery] or prognosis could be demonstrated between the two groups. In contrast, previous appendectomy [n = 18] was associated with penetrating disease and numerically shorter disease duration at the time of resection. Furthermore, a trend was seen towards a stronger association with postoperative recurrence., Conclusion: The current study could not confirm a different prognosis for CD patients with and without an inflamed appendix. In contrast, in patients with a previous appendectomy, a trend was seen towards increased postoperative recurrence, which might be related to the higher incidence of penetrating disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
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- 2024
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22. Clinical statistical analysis plan for the ACCURE trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial.
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Visser E, Heuthorst L, Pathmakanthan S, Bemelman WA, D'Haens GR, Handley K, Fakis A, Pinkney TD, Buskens CJ, and Dijkgraaf MGW
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- Humans, Appendectomy, Quality of Life, Remission Induction, Neoplasm Recurrence, Local, Mesalamine, Recurrence, Disease Progression, Colitis, Ulcerative drug therapy
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Background: The primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial., Design and Methods: The ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life., Discussion: The ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients., Trial Registration: Dutch Trial Register (NTR) NTR2883 . Registered May 3, 2011. ISRCTN, ISRCTN60945764 . Registered August 12, 2019., (© 2024. The Author(s).)
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- 2024
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23. How Reliable Is Endoscopic Scoring of Postoperative Recurrence in Crohn Disease?: A Systematic Review and Meta-Analysis.
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van der Does de Willebois EML, Bellato V, Duijvestein M, van Dieren S, Danese S, Sileri P, Buskens CJ, Vignali A, and Bemelman WA
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Objective: Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications., Methods: A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (<30 included patients), pediatric studies, and letters were excluded. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool were used to assess risk of bias. Main outcome was the range of ER rates within 12 months postoperatively, defined as RS ≥ i2 and/or mRS ≥ i2b. A proportional meta-analysis was performed. The final search was performed on January 4, 2022. The study was registered at PROSPERO, CRD42022363208., Results: Seventy-six studies comprising 7751 patients were included. The weighted mean of ER rates in all included studies was 44.0% (95% confidence interval, 43.56-44.43). The overall range was 5.0% to 93.0% [interquartile range (IQR), 29.2-59.0]. The weighted means for RS and mRS were 44.0% and 41.1%, respectively. The variation in ER rates for RS and mRS were 5.0% to 93.0% (IQR, 29.0-59.5) and 19.8% to 62.9% (IQR, 37.3-46.5), respectively. Within studies reporting both RS and mRS, the weighted means for ER were 61.3% and 40.6%, respectively., Conclusions: This study demonstrates a major variation in ER rates after ICR for CD, suggesting a high likelihood of inadequate diagnosis of disease recurrence, with potentially impact on quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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24. Optimising surgical anastomosis in ileocolic resection for Crohn's disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES).
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Haanappel AEG, Bellato V, Buskens CJ, Armuzzi A, van der Bilt JDW, de Boer NKH, Danese S, van der Does de Willebois EML, Duijvestein M, van der Horst D, Pellino G, Richir MC, Selvaggi F, Spinelli A, Vignali A, Rosati R, and Bemelman WA
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- Humans, Anastomosis, Surgical methods, Colon surgery, Ileum surgery, Quality of Life, Randomized Controlled Trials as Topic, Recurrence, Adolescent, Adult, Crohn Disease surgery
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Background: The most common intestinal operation in Crohn's disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption., Methods: This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs., Discussion: The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines., Trial Registration: NCT05246917 for HAND2END and NCT05578235 for End2End ( http://www., Clinicaltrials: gov/ )., (© 2024. The Author(s).)
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- 2024
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25. Long-term outcomes after appendicectomy as experimental treatment for patients with therapy-refractory ulcerative colitis.
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Reijntjes MA, Heuthorst L, Stellingwerf ME, D'Haens GR, Bemelman WA, and Buskens CJ
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- Humans, Appendectomy, Patients, Colitis, Ulcerative surgery
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- 2024
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26. Viscoelastic properties of small bowel mesentery at MR elastography in Crohn's disease: a prospective cross-sectional exploratory study.
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van Schelt AS, Beek KJ, Wassenaar NPM, Schrauben EM, Runge JH, Gecse KB, van der Bilt JDW, Neefjes-Borst EA, Buskens CJ, Nederveen AJ, and Stoker J
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- Humans, Cross-Sectional Studies, Fibrosis, Mesentery diagnostic imaging, Prospective Studies, Male, Female, Crohn Disease diagnostic imaging, Elasticity Imaging Techniques
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Background: Creeping fat is a pathological feature of small bowel Crohn's disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD., Methods: Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients' mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann-Whitney U-test). Within CD patients, the affected and "presumably" unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland-Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters., Results: SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p < 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%., Conclusion: MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection., Trial Registration: Dutch trial register, NL9105 , registered 7 December 2020., Relevance Statement: MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn's disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection., Key Points: • MRE of the mesentery in patients with active CD is feasible. • Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis. • MRE provides biomarkers to quantify mesenteric disease activity in active CD., (© 2023. European Society of Radiology (ESR).)
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- 2023
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27. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial.
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Meima-van Praag EM, Becker MAJ, van Rijn KL, Wasmann KATGM, Stoker J, D'Haens GRAM, Ponsioen CY, Gecse KB, Dijkgraaf MGW, Spinelli A, Danese S, Bemelman WA, and Buskens CJ
- Abstract
Background: The PISA-II trial showed that short-term anti-tumour necrosis factor (anti-TNF) therapy followed by surgical closure induces radiological healing of perianal fistulas in patients with Crohn's disease more frequently than anti-TNF therapy alone after 18 months. This study aimed to compare long-term outcomes of both treatment arms., Methods: Follow-up data were collected from patients who participated in the PISA-II trial, an international patient preference randomised controlled trial. This multicentre trial was performed in nine hospitals in the Netherlands and one hospital in Italy. Patients with Crohn's disease above the age of 18 years with an active high perianal fistula and a single internal opening were asked to participate. Patients were allocated to anti-TNF therapy (intravenous infliximab, or subcutaneous adalimumab, at the discretion of the gastroenterologist) for one year, or surgical closure combined with 4-months anti-TNF therapy. Patients without a treatment preference were randomised (1:1) using random block randomisation (block sizes of six without stratification), and patients with a treatment preference were treated according to their preferred treatment arm. For the current follow-up study, data were collected until May 2022. Primary outcome was radiological healing on magnetic resonance imaging (MRI), including all participants with a MRI made less than 6 months ago at the time of data collection. Analysis was based on observed data., Findings: Between September 14, 2013, and December 7, 2019, 94 patients were enrolled in the trial. Long-term follow-up data were available in 91 patients (36/38 (95%) anti-TNF + surgical closure, 55/56 (98%) anti-TNF). A total of 14/36 (39%) patients in the surgical closure arm were randomly assigned, which was not significantly different in the anti-TNF treatment arm (16/55 (29%) randomly assigned). Median follow-up was 5.7 years (interquartile range (IQR) 5-7). Radiological healing occurred significantly more often after anti-TNF + surgical closure (15/36 = 42% versus 10/55 = 18%; P = 0.014). Clinical closure was comparable (26/36 = 72% versus 34/55 = 62%; P = 0.18) in both groups. However, clinical closure in the surgical group was achieved with less re-interventions 4/26 (= 15%) versus 18/34 (= 53%), including (redo-)surgical closure procedures. Recurrences occurred in 0/25 (0%) patients with radiological healing versus 27/76 (36%) patients with clinical closure, sometime during follow-up. Anti-TNF trough levels were higher in patients with long-term clinical closure in both groups (P = 0.031 and P = 0.014). In 6/11 (55%) patients in the anti-TNF group with available trough levels, recurrences were diagnosed within three months of a drop under 3.5ug/ml. 36 patients stopped anti-TNF, after which 0/14 (0%) patients with radiological healing developed a recurrence and 9/22 (41%) with clinical closure. Self-rated (in)continence was comparable between groups, and 79% (60/76) of patients indicated comparable/improved continence after treatment. Decision-regret analysis showed that all (30/30) anti-TNF + surgical closure patients agreed or strongly agreed that surgery was the right decision versus 78% (36/46) in the anti-TNF arm. All surgical closure patients would go for the same treatment again, whereas this was 89% (41/46) in the anti-TNF arm., Interpretation: This study confirmed that surgical closure should be considered in amenable patients with perianal fistulas and Crohn's disease as long-term outcomes were favourable, and that radiological healing should be the aim of treatment as recurrences only occurred in patients without radiological healing. In patients with complete MRI closure, anti-TNF could be safely stopped., Funding: None., Competing Interests: EMMP, MAJB, KLR, KATGMW, JS, MGWD, and AS have nothing to declare. GRH has received grants from Bristol Meiers Squibb, Pfizer and Takeda, has served as a consultant and/or received speaker's fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, Glaxo SmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts, Ventyx Biosciences. He furthermore received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Boehringer Ingelheim, Takeda and Abbvie, and participated on a Data Safety Monitoring Board or Advisory Board of Astrazeneca, Abbvie and Seres Health. CYP has received grants from Perspectum and Gilead; consulting fees from Shire, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Tillotts. KBG has received grants from Pfizer, Galapagos, Celltrion, consultancy fees from. AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda, and speaker's honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts. SD has received consulting fees from Abbvie, Alimentiv, Allergan, Amgen, AstraZaneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial and Vifor. He furthermore received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer and Takeda. WAB has received grants from Braun and Vifor, and has served as speaker for Takeda, Johnson and Johnson and Braun. CJB has an unrestricted grant from Boehringer Ingelheim and Roche. She has also received consultancy fees and/or speaker's honoraria from AbbVie, MSD, Tillotts, Janssen and Takeda., (© 2023 The Authors. Published by Elsevier Ltd.)
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- 2023
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28. Temporary diverting stoma in therapy-refractory luminal colonic Crohn's disease: an alternative to immediate colorectal resection?
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van der Holst AM, Otten AT, Praag EMM, van Renterghem ARPKM, Bourgonje AR, van Loo ES, Dijkstra G, Buskens CJ, and Stassen LPS
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- Humans, Ileostomy methods, Retrospective Studies, Cohort Studies, Crohn Disease complications, Crohn Disease surgery, Proctitis, Colorectal Neoplasms complications
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Aim: Creation of a diverting stoma in patients with Crohn's disease (CD) can counteract luminal inflammation. The clinical utility of a diverting stoma with the prospect of restoration of gastrointestinal continuity warrants further investigation. The aim of this work was to evaluate the long-term effects of creation of a diverting stoma on the disease course in patients with luminal colonic CD., Method: In this retrospective, multicentre cohort study we investigated the disease course of patients who received a diverting stoma in the biological era. Clinical characteristics, medication use and surgical course were assessed at the time of creation of the diverting stoma and during follow-up. The primary outcome was the rate of successful and lasting reestablishment of gastrointestinal continuity., Results: Thirty six patients with refractory luminal CD from four institutions underwent creation of a diverting stoma. Of the overall cohort, 20 (56%) patients had their gastrointestinal continuity reestablished after initial stoma creation and 14 (39%) who had their stoma reversed remained stoma-free during a median of 3.3 years follow-up (interquartile range 2.1-6.1 years). Absence of stoma reversal was associated with the presence of proctitis (p = 0.02). Colorectal resection after creation of a diverting stoma was performed in 28 (78%) patients, with 7 (19%) having a less extensive resection and 6 (17%) having a more extensive resection compared with the surgical plan before stoma creation., Conclusion: A diverting stoma could potentially be an alternative to immediate definitive stoma placement in specific populations consisting of patients with luminal colonic CD, especially in the absence of proctitis., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)
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- 2023
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29. Endoscopic Recurrence or Anastomotic Wound Healing Phenomenon after Ileocolic Resection for Crohn's Disease: The Challenges of Accurate Endoscopic Scoring.
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van der Does de Willebois EML, Duijvestein M, Wasmann KA, D'Haens GRAM, van der Bilt JDW, Mundt MW, Hompes R, van der Vlugt M, Buskens CJ, and Bemelman WA
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- Humans, Prospective Studies, Quality of Life, Ileum surgery, Colon surgery, Anastomosis, Surgical adverse effects, Colonoscopy, Recurrence, Retrospective Studies, Crohn Disease surgery, Crohn Disease etiology
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Background and Aims: Adequate endoscopic scoring in Crohn's disease [CD] is crucial, as it dictates the need for initiating postoperative medical therapy and is utilized as an outcome parameter in clinical trials. Here we aimed to observe anastomotic wound healing in relation to endoscopic scoring of both inverted and everted stapled lines in side-to-side anastomoses., Methods: Two prospective patient cohorts were included: ileocolic resection [ICR] for CD, and right-sided colon resection for colorectal cancer [CRC]. Videos taken during colonoscopy 6 months postoperatively were evaluated. The Simplified Endoscopic Activity Score for Crohn's Disease and modified Rutgeerts score were determined. The primary outcome was the presence of ulcerations in CD patients on both the inverted and the everted stapled lines. Secondary outcomes were the presence of anastomotic ulcerations in CRC patients and the number of cases having ulcerations exclusively at the inverted stapled line., Results: Of the 82 patients included in the CD cohort, ulcerations were present in 63/82 [76.8%] at the inverted- vs 1/71 [1.4%] at the everted stapled line. Likewise in the CRC cohort, ulcerations were present in 4/6 [67.7%] at the inverted vs 0/6 [0%] at the everted stapled line. In total, 27% of the 63 patients in the CD cohort had ulcerations exclusively on the inverted stapled line., Conclusion: Inverted stapled lines heal with ulcerations, whereas everted stapled lines heal without any ulcerations, in both CD and non-CD patients. The abnormalities at the inverted stapled line might interfere with endoscopic scoring of recurrence, with potentially an impact on patients' quality of life and on healthcare costs if postoperative treatment is initiated incorrectly., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
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- 2023
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30. Increased Proportion of Colorectal Cancer in Patients With Ulcerative Colitis Undergoing Surgery in the Netherlands.
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Heuthorst L, Harbech H, Snijder HJ, Mookhoek A, D'Haens GR, Vermeire S, D'Hoore A, Bemelman WA, and Buskens CJ
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- Humans, Netherlands epidemiology, Colectomy adverse effects, Colitis, Ulcerative epidemiology, Colitis, Ulcerative surgery, Colitis, Ulcerative complications, Colorectal Neoplasms epidemiology, Colorectal Neoplasms surgery, Colorectal Neoplasms etiology
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Introduction: The aim of the current study was to assess whether there is an indication shift for surgery in patients with ulcerative colitis (UC) from refractory disease to malignant degeneration over the past 3 decades., Methods: All patients with histologically confirmed UC who underwent a colorectal resection between 1991 and 2020 were extracted from the nationwide Dutch Pathology Registry. The primary outcome was the proportion of colorectal cancer (CRC) in the colon specimens. Outcomes were compared between 3 periods (P1: 1991-2000, P2: 2001-2010, and P3: 2011-2020)., Results: Overall, 6,094 patients with UC were included of which 4,854 underwent a (procto)colectomy and 1,240 a segmental resection. In 1,031 (16.9%) patients, CRC was demonstrated in the pathological resection specimen after a median disease duration of 11 years (IQR 3.0-19.0). The proportion of CRC increased from 11.3% in P1, to 16.1% in P2, and 22.8% in P3 ( P < 0.001). Median disease duration at the time of resection increased from 4 years in P1, to 10 years in P2, and 17 years in P3 ( P < 0.001). The proportion of patients diagnosed with advanced malignancy (pT3/T4) (P1: 61.2% vs P2: 65.2% vs P3: 62.4%, respectively, P = 0.633) and lymph node metastasis (N+) (P1: 33.0% vs P2: 41.9% vs P3: 38.2%, respectively, P = 0.113) did not change over time., Discussion: This nationwide pathology study demonstrated an increased proportion of surgery for CRC over the past 3 decades. We hypothesize that the expanding therapeutic armamentarium for UC leads to exhausting medical options and hence postponed colectomy. This, however, might be at the expense of an increased risk of CRC in the long term., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)
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- 2023
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31. Fluorescence perfusion assessment of vascular ligation during ileal pouch-anal anastomosis.
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Slooter MD, van der Does de Willebois EML, Joosten JJ, Reijntjes MA, Buskens CJ, Tanis PJ, Bemelman WA, and Hompes R
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- Humans, Male, Middle Aged, Female, Retrospective Studies, Anastomosis, Surgical, Ileum surgery, Perfusion, Postoperative Complications surgery, Proctocolectomy, Restorative methods, Colonic Pouches, Colitis, Ulcerative surgery
- Abstract
Background: Intraoperative fluorescence angiography (FA) is of potential added value during ileal pouch-anal anastomosis (IPAA), especially after vascular ligation as part of lengthening measures. In this study, time to fluorescent enhancement during FA was evaluated in patients with or without vascular ligation during IPAA., Methods: This is a retrospective cohort study of all consecutive patients that underwent FA-guided IPAA between August 2018 and December 2019 in our tertiary referral centre. Vascular ligation was defined as disruption of the ileocolic arcade or ligation of interconnecting terminal ileal branches. FA was performed before and after ileoanal anastomotic reconstruction. During FA, time to fluorescent enhancement was recorded at different sites of the pouch., Results: Thirty-eight patients [55.3% male, median age 45 years (IQR 24-51 years)] were included, of whom the majority (89.5%) underwent a modified-2-stage restorative proctocolectomy. Vascular ligation was performed in 15 patients (39.5%), and concerned central ligation of the ileocolic arcade in 3 cases, interconnecting branches in 10, and a combination in 2. For the entire cohort, time between indocyanine green (ICG) injection and first fluorescent signal in the pouch was 20 s (IQR 15-31 s) before and 25 s (IQR 20-36 s) after anal anastomotic reconstruction. Time from ICG injection to the first fluorescent signal at the inlet, anvil and blind loop of the pouch were non-significantly prolonged in patients that received vascular ligation., Conclusions: Results from this study indicate that time to fluorescence enhancement during FA might be prolonged due to arterial rerouting through the arcade or venous outflow obstruction in case of vascular ligation., (© 2022. The Author(s).)
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- 2023
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32. Classification of surgical causes of and approaches to the chronically failing ileoanal pouch.
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Meima-van Praag EM, Reijntjes MA, Hompes R, Buskens CJ, Duijvestein M, and Bemelman WA
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- Adult, Humans, Male, Middle Aged, Female, Retrospective Studies, Rectum surgery, Postoperative Complications etiology, Colonic Pouches adverse effects, Proctocolectomy, Restorative methods, Colitis, Ulcerative surgery
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Background: Although there are various surgical causes of and therapeutic approaches to the chronically failing ileoanal pouch (PF), cases are often detailed without distinguishing the exact cause and corresponding treatment. The aim of our study was to classify causes of PF and corresponding surgical treatment options, and to establish efficacy of surgical approach per cause., Methods: This retrospective study included all consecutive adult patients with chronic PF surgically treated at our tertiary hospital between July 2014 and March 2021. Patients were classified according to a proposed sub-classification for surgical related chronic PF. Results were reported accordingly., Results: A total of 59 procedures were completed in 50 patients (64% male, median age 45 years [IQR 34.5-54.3]) for chronic PF. Most patients had refractory ulcerative colitis as indication for their restorative proctocolectomy (68%). All patients could be categorized according to the sub-classification. Reasons for chronic PF were septic complications (n = 25), pouch body complications (n = 12), outlet problems (n = 11), cuff problems (n = 8), retained rectum (n = 2), and inlet problems (n = 1). For these indications, 17 pouches were excised, 10 pouch reconstructions were performed, and 32 pouch revision procedures were performed. The various procedures had different complication rates. Technical success rates of redo surgery for the different causes varied from 0 to 100%, with a 75% success rate for septic causes., Conclusions: Our sub-classification for chronic PF and corresponding treatments is suitable for all included patients. Outcomes varied between causes and subsequent management. Chronic PF was predominantly caused by septic complications with redo surgery achieving a 75% technical success rate., (© 2022. The Author(s).)
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- 2023
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33. Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.
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Talboom K, Borstlap WAA, Roodbeen SX, Bruns ERJ, Buskens CJ, Hompes R, Tytgat KMAJ, Tuynman JB, Consten ECJ, Heuff G, Kuiper T, van Geloven AAW, Veldhuis GJ, van der Hoeven JAB, Gerhards MF, Sietses C, Spinelli A, van de Ven AWH, van der Zaag ES, Westerterp M, van Westreenen HL, Dijkgraaf ML, Juffermans NP, and Bemelman WA
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- Adult, Male, Humans, Female, Iron, Hemoglobins, Dietary Supplements, Anemia, Iron-Deficiency etiology, Anemia, Iron-Deficiency complications, Colorectal Neoplasms complications, Colorectal Neoplasms drug therapy, Colorectal Neoplasms surgery
- Abstract
Background: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia., Methods: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment., Findings: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202)., Interpretation: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation., Funding: Vifor Pharma., Competing Interests: Declaration of interests WAB received funding from Vifor Pharma for this trial. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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34. Long-term outcomes after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis for ulcerative colitis.
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Reijntjes MA, de Jong DC, Bartels S, Wessels EM, Bocharewicz EK, Hompes R, Buskens CJ, d'Haens GR, Duijvestein M, and Bemelman WA
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- Male, Humans, Adult, Middle Aged, Retrospective Studies, Quality of Life, Anastomosis, Surgical adverse effects, Postoperative Complications etiology, Treatment Outcome, Colitis, Ulcerative surgery, Proctocolectomy, Restorative methods, Rectal Neoplasms surgery, Colonic Pouches adverse effects
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Background: During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME., Methods: This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score., Results: Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03)., Conclusions: Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC., (© 2022. The Author(s).)
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- 2023
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35. Platelet-Rich stroma from Crohn's disease patients for treatment of perianal fistula shows a higher myeloid cell profile compared to non-IBD controls.
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Arkenbosch JHC, Becker MAJ, Buskens CJ, Witjes C, de Vries AC, van der Woude CJ, Fuhler G, Wildenberg ME, and van Ruler O
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- Male, Female, Humans, Adipose Tissue, Myeloid Cells, Crohn Disease, Rectal Fistula therapy
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Background: New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls., Methods: Consecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis., Results: Twenty-three patients (37.8 [IQR 30.7-45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.62*10
5 cells/mL versus non-IBD 12.20 ± 3.39*105 ). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples., Conclusions: The composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn's disease does not appear to alter the immunological composition of adipose-derived products., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.J. Buskens has served on the advisory board for Johnson&Johnson energy devices; and has received consultancy fees and/or speaker’s honoraria from AbbVie, Boehringer Ingelheim, Janssen and Takeda, outside the submitted work. Annemarie C. de Vries has served on the advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, Galapagos; and has received unrestricted research grants from Takeda, Janssen, Pfizer, outside the submitted work. C. Janneke van der Woude received grants and or fee for advisory boards and presentations from Pfizer, Abbvie, Celltrion, Falk Benelux, Takeda, Janssen, and Ferring, outside the submitted work. M.E. Wildenberg received research grants from Boehringer Ingelheim, Roche and GSK, outside the submitted work. Oddeke van Ruler has served as invited speaker for Janssen-Cilag; and has received a research grant from Takeda, outside the submitted work. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2023
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36. Editorial: routine use of intestinal ultrasound in ulcerative colitis-are we missing the appendix? Authors' reply.
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Reijntjes MA, de Voogd FAE, Buskens CJ, and Gecse KB
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- Humans, Intestines, Ultrasonography, Colitis, Ulcerative diagnostic imaging, Appendix
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- 2023
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37. Intestinal ultrasound detects an increased diameter and submucosal layer thickness in the appendix of patients with ulcerative colitis compared to healthy controls - a prospective cohort study.
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Reijntjes MA, de Voogd FAE, Bemelman WA, Hompes R, d'Haens G, Buskens CJ, and Gecse KB
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- Humans, Prospective Studies, Colitis, Ulcerative diagnostic imaging, Ultrasonography
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Background: Increasing evidence suggests that appendicectomy as alternative treatment for ulcerative colitis (UC), especially in patients with histopathological appendiceal inflammation. Intestinal ultrasound (IUS) is a non-invasive diagnostic modality to characterise appendiceal inflammation., Aims: To assess appendiceal IUS characteristics in UC patients and compare findings to healthy controls (HC)., Methods: In this prospective study, appendiceal IUS was performed in consecutive UC patients with active (A; n = 35) or quiescent (Q; n = 30) disease and in HC (n = 30). Transverse appendiceal diameter (TAD) and additional IUS parameters (bowel wall thickness, submucosal layer thickness and colour Doppler signal) were assessed., Results: The appendix was visualised in 41/65 UC patients (63.1%; A vs. Q: 23/35 vs. 18/30, p = 0.67) and 18/30 (60%) HC. UC patients had a higher TAD (A: 5.5 mm, Q: 5.0 mm, HC: 4.3 mm; A-HC p < 0.01; Q-HC p = 0.01, A-Q p = ns) and submucosal layer thickness (A: 1.0 mm, Q: 1.0 mm, HC: 0.7 mm; A-HC p < 0.01, Q-HC: p = 0.01, A-Q: p = ns) when compared to HC. A TAD ≥6 mm corresponding to an ultrasonographic suspicion of acute appendicitis was mainly reported in A-UC patients (A: 43%; Q: 6%; HC: 0%, p = 0.01) and occurred irrespective of disease extent. However, none of the patients had a clinical suspicion of acute appendicitis., Conclusion: A TAD ≥6 mm was predominantly seen in A-UC. TAD was higher in UC patients compared to HC irrespective of disease activity and was characterised by an increased submucosal layer thickness. IUS therefore has the potential to identify UC patients with appendiceal inflammation., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
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- 2023
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38. Incidence and causes of failure in various anatomical pouch designs 20 years after surgical primary ileal-pouch anal anastomosis construction.
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Reijntjes MA, Bocharewicz EK, Hompes R, Buskens CJ, and Bemelman WA
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- Humans, Retrospective Studies, Ileostomy adverse effects, Anastomosis, Surgical adverse effects, Anastomosis, Surgical methods, Postoperative Complications etiology, Postoperative Complications surgery, Colitis, Ulcerative surgery, Proctocolectomy, Restorative adverse effects, Proctocolectomy, Restorative methods, Colonic Pouches adverse effects
- Abstract
Purpose: Since the introduction of ileo-pouch anal anastomosis (IPAA) surgery, various pouch designs have been applied. Recently, there has been renewed interest in creating larger pouch designs to reduce defecation frequency after pouch surgery. The aim of this study was to assess chronic pouch failure (PF) rates and causes in alternative S or septated (SP) pouches when compared to J pouches and B- shaped adaptations., Methods: This retrospective cohort study included patients that underwent primary IPAA construction surgery from 1978-2000. Pouch designs were subdivided in J and B (J/B), and larger pouches (S/SP). PF included need for a pouch excision, redo pouch procedure, revisional pouch surgery, or permanent ileostomy surgery. Outcomes of this study were incidence and causes for PF per pouch design group., Results: Out of 200 patients who underwent IPAA surgery, 19 had an S/SP design and 181 had a J/B design. After a follow-up of 27.0 (IQR 23.3 - 29.0) years, 45/200 (22.5%) patients who underwent IPAA surgery between 1975-2000 developed PF. Some 78.9% of patients with an S/SP pouch developed PF, compared to 16.7% of patients with a J/B pouch (p < 0.01). Mechanical outlet issues occurred more often in S/SP pouches when compared to J/B (42.1% vs. 1.1%, p < 0.01), and were predominantly caused by septal- or pouch wall intussusception and efferent loop kinking (S-pouch)., Conclusion: Despite an inevitable proportion of bias, the current study revealed that S/SP pouches were characterized by an increased PF incidence due to emptying problems after long-term follow-up when compared to J/B pouches. Constructing an S pouch or large septated reservoir at index surgery should therefore be questioned because of a shorter longevity., (© 2022. The Author(s).)
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- 2022
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39. A BET Protein Inhibitor Targeting Mononuclear Myeloid Cells Affects Specific Inflammatory Mediators and Pathways in Crohn's Disease.
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Elfiky AMI, Hageman IL, Becker MAJ, Verhoeff J, Li Yim AYF, Joustra VW, Mulders L, Fung I, Rioja I, Prinjha RK, Smithers NN, Furze RC, Mander PK, Bell MJ, Buskens CJ, D'Haens GR, Wildenberg ME, and de Jonge WJ
- Subjects
- Carboxylic Ester Hydrolases, Humans, Inflammation Mediators, Interleukin-6, Myeloid Cells metabolism, NF-kappa B, Proto-Oncogene Proteins c-akt, RNA, Tumor Necrosis Factor-alpha, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Crohn Disease drug therapy, Crohn Disease metabolism
- Abstract
Background: Myeloid cells are critical determinants of the sustained inflammation in Crohn's Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities. In the current study, we make use of a BET inhibitor containing an esterase sensitive motif (ESM-iBET), which is cleaved by carboxylesterase-1 (CES1), a highly expressed esterase in mononuclear myeloid cells., Methods: We profiled CES1 protein expression in the intestinal biopsies, peripheral blood, and CD fistula tract (fCD) cells of CD patients using mass cytometry. The anti-inflammatory effect of ESM-iBET or its control (iBET) were evaluated in healthy donor CD14
+ monocytes and fCD cells, using cytometric beads assay or RNA-sequencing., Results: CES1 was specifically expressed in monocyte, macrophage, and dendritic cell populations in the intestinal tissue, peripheral blood, and fCD cells of CD patients. ESM-iBET inhibited IL1β, IL6, and TNFα secretion from healthy donor CD14+ monocytes and fCD immune cells, with 10- to 26-fold more potency over iBET in isolated CD14+ monocytes. Transcriptomic analysis revealed that ESM-iBET inhibited multiple inflammatory pathways, including TNF, JAK-STAT, NF-kB, NOD2, and AKT signaling, with superior potency over iBET., Conclusions: We demonstrate specific CES1 expression in mononuclear myeloid cell subsets in peripheral blood and inflamed tissues of CD patients. We report that low dose ESM-iBET accumulates in CES1-expressing cells and exerts robust anti-inflammatory effects, which could be beneficial in refractory CD patients.- Published
- 2022
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40. Analyzing and Discussing Human Factors Affecting Surgical Patient Safety Using Innovative Technology: Creating a Safer Operating Culture.
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van Dalen ASHM, Jung JJ, Nieveen van Dijkum EJM, Buskens CJ, Grantcharov TP, Bemelman WA, and Schijven MP
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- Cross-Sectional Studies, Humans, Medical Errors prevention & control, Operating Rooms, Patient Care Team, Patient Safety, Safety Management
- Abstract
Introduction: Surgical errors often occur because of human factor-related issues. A medical data recorder (MDR) may be used to analyze human factors in the operating room. The aims of this study were to assess intraoperative safety threats and resilience support events by using an MDR and to identify frequently discussed safety and quality improvement issues during structured postoperative multidisciplinary debriefings using the MDR outcome report., Methods: In a cross-sectional study, 35 standard laparoscopic procedures were performed and recorded using the MDR. Outcome data were analyzed using the automated Systems Engineering Initiative for Patient Safety model. The video-assisted MDR outcome report reflects on safety threat and resilience support events (categories: person, tasks, tools and technology, psychical and external environment, and organization). Surgeries were debriefed by the entire team using this report. Qualitative data analysis was used to evaluate the debriefings., Results: A mean (SD) of 52.5 (15.0) relevant events were identified per surgery. Both resilience support and safety threat events were most often related to the interaction between persons (272 of 360 versus 279 of 400). During the debriefings, communication failures (also category person) were the main topic of discussion., Conclusions: Patient safety threats identified by the MDR and discussed by the operating room team were most frequently related to communication, teamwork, and situational awareness. To create an even safer operating culture, educational and quality improvement initiatives should aim at training the entire operating team, as it contributes to a shared mental model of relevant safety issues., Competing Interests: Dr Grantcharov holds intellectual property ownership of Surgical Safety Technologies Inc, is the founder of the OR Black Box, and is supported by research grants from Medtronic Canada, Ethicon Canada, Baxter Canada, Olympus Canada, Takeda Canada, and Intuitive Canada. Dr Jung receives consulting fee from Surgical Safety Technologies Inc. Dr Schijven has no conflicts of interest but has been appointed as affiliate scientist to the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto. Drs van Dalen, Dr. Buskens, Dr. Nieveen van Dijkum, and Dr. Bemelman have no conflicts of interest or financial ties considered relevant to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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41. Role of the Mesentery in Crohn's Terminal Ileitis.
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Becker MAJ, Does de Willebois EMLV, Bemelman WA, Wildenberg ME, and Buskens CJ
- Abstract
Despite the longstanding awareness of the presence of mesenteric alterations in Crohn's disease, the functional and clinical consequences of these alterations remain a topic of debate. Guidelines advise a limited resection without resection of the adjacent mesentery to prevent short bowel syndrome and postoperative complications. However, recently mesenteric resection has been proposed as an alternative to reduce recurrence rates in Crohn's disease patients. Here, we evaluate the data available on this topic in terminal ileitis, both from a fundamental research point of view and clinical perspective., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)
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- 2022
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42. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial.
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Meima-van Praag EM, van Rijn KL, Wasmann KATGM, Snijder HJ, Stoker J, D'Haens GR, Gecse KB, Gerhards MF, Jansen JM, Dijkgraaf MGW, van der Bilt JDW, Mundt MW, Spinelli A, Danese S, Bemelman WA, and Buskens CJ
- Subjects
- Adult, Humans, Patient Preference, Quality of Life, Treatment Outcome, Tumor Necrosis Factor Inhibitors therapeutic use, Tumor Necrosis Factor-alpha, Crohn Disease complications, Crohn Disease drug therapy, Crohn Disease surgery, Rectal Fistula drug therapy, Rectal Fistula etiology, Rectal Fistula surgery
- Abstract
Background: Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone., Methods: The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion., Findings: Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment., Interpretation: Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach., Funding: Netherlands Organisation for Health Research and Development and Broad Medical Research Program., Competing Interests: Declaration of interests GRD'H reports grants from Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, Pfizer, Johnson & Johnson, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, and Progenity; consulting fees from AbbVie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, GlaxoSmithKline, Gossamerbio, Pfizer, Immunic, Johnson & Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, Protagonist; and speaker's honoraria from AbbVie, Merck Sharp & Dohme, Tillotts, Janssen, Takeda, Pfizer, and Bristol Myers Squibb. GRD'H participated on a Data Safety Monitoring Board or Advisory Board for Galapagos, Astrazeneca, and AbbVie. KBG reports grants from Pfizer, Galapagos, and Celltrion; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, and Takeda; consulting fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, and Takeda; and speaker's honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, Takeda, and Tillotts. SD reports consulting fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZaneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor. WAB has served as speaker for Takeda, Johnson & Johnson, and Braun; and reports research grants from Braun and Vifor. CJB has an unrestricted grant from Boehringer Ingelheim and Roche; reports consultancy fees or speaker's honoraria from AbbVie, Merck Sharp & Dohme, Tillotts, Janssen, and Takeda. All other authors declared no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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43. Clinical relevance of endoscopic peri-appendiceal red patch in ulcerative colitis patients.
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Reijntjes MA, Heuthorst L, Gecse K, Mookhoek A, Bemelman WA, and Buskens CJ
- Abstract
Background: Increasing evidence is suggesting appendectomy as an alternative treatment for ulcerative colitis (UC), especially in case of histological appendiceal inflammation. Therefore, preoperative identification of appendiceal inflammation could be beneficial. This study aimed to assess the prevalence of peri-appendiceal red patch (PARP) on colonoscopy. In addition, prognostic relevance of PARP for disease course and its predictive value for histological appendiceal inflammation in patients undergoing appendectomy was assessed., Methods: UC patients undergoing colonoscopy in 2014/2015 were included to determine PARP-prevalence in a cross-sectional study. Findings were correlated to patient and disease characteristics, upscaling of treatment and colectomy rates after cross-sectional colonoscopy. In patients undergoing appendiceal resection, histopathological inflammation was assessed using the Robarts Histopathology Index (RHI)., Results: In total, 249 patients were included of which 17.7% (44/249) had a PARP. Patients with PARP were significantly younger with a shorter disease course. The majority of patients with PARP (61.4%) was in endoscopic remission. Patients with PARP required more upscaling of medical therapy (81.8% vs . 58.0%, p < 0.01), and more PARP patients underwent colectomy (13.6% vs . 4.9%, p = 0.04). Patients with PARP had a higher median RHI in resection specimens (14 vs . 7, p < 0.01)., Conclusion: PARP was present during colonoscopy regardless disease activity and was predominantly found in UC patients with younger age and shorter disease duration. PARP patients had a more severe course of UC, and in case of appendectomy, more severe histopathological appendiceal inflammation. Appendectomy as an experimental therapy for UC has been suggested to be predominantly effective in UC patients with appendiceal inflammation. This study demonstrates that presence of a PARP on colonoscopy predicts appendiceal inflammation. After consensus has been reached on the therapeutic effect of appendectomy, assessing PARP presence during colonoscopy could therefore contribute to identifying patients most likely to respond., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)
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- 2022
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44. Fibrosis and MAGNIFI-CD Activity Index at Magnetic Resonance Imaging to Predict Treatment Outcome in Perianal Fistulizing Crohn's Disease Patients.
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van Rijn KL, Meima-van Praag EM, Bossuyt PM, D'Haens GR, Gecse KB, Horsthuis K, Snijder HJ, Tielbeek JAW, Buskens CJ, and Stoker J
- Subjects
- Adult, Female, Fibrosis, Humans, Magnetic Resonance Imaging, Retrospective Studies, Treatment Outcome, Tumor Necrosis Factor Inhibitors, Tumor Necrosis Factor-alpha, Crohn Disease complications, Crohn Disease diagnostic imaging, Crohn Disease drug therapy, Cutaneous Fistula, Rectal Fistula diagnostic imaging, Rectal Fistula etiology, Rectal Fistula therapy
- Abstract
Background and Aims: Characteristic magnetic resonance imaging [MRI] features associated with long-term perianal fistula closure are still being discussed. This study evaluated the predictive value of degree of fibrosis and disease activity (MAGNIFI-CD index) at MRI for long-term clinical closure of Crohn's perianal fistulas., Methods: Crohn's disease [CD] patients treated with surgical closure following anti-tumour necrosis factor [anti-TNF] induction or anti-TNF alone for high perianal fistulas as part of a patient preference randomized controlled trial [PISA-II] between 2013 and 2020 with a post-treatment MRI and long-term clinical follow-up data were retrospectively included. Two radiologists scored the degree of fibrosis and MAGNIFI-CD index at pre- and post-treatment MRI. The accuracy of post-treatment MRI findings in predicting long-term clinical closure [12 months after the MRI] was evaluated using receiver operating characteristics [ROC] analysis., Results: Fifty patients were included: 31 female, median age 33 years (interquartile range [IQR] 26-45). Fourteen patients showed a 100% fibrotic fistula at post-treatment MRI, all of which had long-term clinical closure. Median MAGNIFI-CD index at post-treatment MRI was 0 [IQR 0-5] in 25 patients with long-term clinical closure and 16 [IQR 10-20] in 25 patients without. ROC analysis showed an area under the curve of 0.90 (95% confidence interval [CI] 0.82-0.99) for degree of fibrosis and 0.95 [95% CI 0.89-1.00] for the MAGNIFI-CD index, with a Youden cut-off point of 6 [91% specificity, 87% sensitivity]., Conclusions: Degree of fibrosis and MAGNIFI-CD index at post-treatment MRI are accurate in predicting long-term clinical closure and seem valuable in follow-up of perianal CD. A completely fibrotic tract at MRI is a robust indicator for long-term fistula closure., Eudract: 2013-002932-25 and 2018-002064-15., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
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- 2022
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45. Author response to: Mesenteric SParIng versus extensive mesentereCtomY in primary ileocolic resection for ileocaecal Crohn's disease (SPICY): study protocol for randomized controlled trial.
- Author
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Van der Does de Willebois EML and Buskens CJ
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- 2022
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46. Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease: Results of the HOT-TOPIC trial after 1-year follow-up.
- Author
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Lansdorp CA, Buskens CJ, Gecse KB, Löwenberg M, Stoker J, Bemelman WA, D'Haens GRAM, and van Hulst RA
- Subjects
- Adult, Female, Follow-Up Studies, Humans, Treatment Outcome, Crohn Disease complications, Crohn Disease diagnosis, Crohn Disease therapy, Hyperbaric Oxygenation, Rectal Fistula diagnosis, Rectal Fistula etiology, Rectal Fistula therapy
- Abstract
Background: Previously published short-term results (week 16) of this trial showed a significant improvement in clinical, radiologic and biochemical outcomes in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen therapy., Objective: To assess the long-term (week 60) efficacy, safety and feasibility of hyperbaric oxygen therapy in perianal fistula in Crohn's disease., Methods: Crohn's disease patients with high perianal fistula(s) failing conventional treatment >6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received 40 hyperbaric oxygen sessions and outcomes were assessed at week 16 and week 60., Results: Twenty patients were included (median age 34 years). At week 16, median scores of the perianal disease activity index and modified Van Assche index (co-primary outcomes) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, p < 0.001) and 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, p = 0.004), respectively. At week 60, the respective scores remained significantly lower than baseline: 4 (95% CI 3-7, p < 0.001) and 7.7 (95% CI 5.2-10.2, p = 0.003). Perianal disease activity index score of 4 or less (representing inactive perianal disease) was observed in 13 patients at week 16 and 12 patients at week 60. Using fistula drainage assessment, 12 and 13 patients showed a clinical response at week 16 and 60, respectively, and clinical remission was achieved in four patients for both time points. At week 16, a statistically significant biochemical improvement (C-reactive protein and faecal calprotectin levels) was found, but this effect was no longer significant at week 60., Conclusions: The clinical and radiologic improvement of perianal fistula in Crohn's disease, that was found at week 16 after treatment with hyperbaric oxygen therapy, is maintained at 1-year follow-up., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)
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- 2022
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47. The "Phillips" Ileostomy Correction Technique for Prolapsed Stoma.
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Bellato V, Tanis PJ, Hompes R, Buskens CJ, Sica GS, and Bemelman WA
- Subjects
- Adult, Female, Humans, Intestinal Diseases surgery, Male, Middle Aged, Prolapse, Risk Factors, Treatment Outcome, Crohn Disease surgery, Ileostomy adverse effects, Ileostomy methods, Postoperative Complications diagnosis, Postoperative Complications etiology, Postoperative Complications surgery, Proctocolectomy, Restorative adverse effects, Proctocolectomy, Restorative methods, Reoperation methods, Surgical Stomas adverse effects
- Abstract
Introduction: Stoma prolapse is a common complication associated with ostomy creation, causing leakage, obstruction, and sometimes incarceration. Sometimes ileostomy prolapse cannot be treated with resection and alternative methods must be applied. We propose a new surgical revisional technique for ileostomy prolapse., Technique: Under general anesthesia, the prolapsed stoma is dissected and freed from the fascia and skin. The bowel is everted to create a nipple of 2-3 cm and subsequently fixed with a 3-row linear stapler, creating a "Phillips ileostomy." The ileostomy is then sutured to the skin with 3-0 full thickness stitches., Results: In our center, 3 patients were treated in a day surgery setting, and no complication occurred. One patient reported a prolapse recurrence after 6 months and was successfully treated with the same technique with no recurrence at 1 year., Conclusions: The 3-row stapler fixation of prolapsed ileostomy is simple to perform, preserves the bowel, and can be performed in the day surgery setting., (Copyright © The ASCRS 2022.)
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- 2022
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48. High prevalence of ulcerative appendicitis in patients with ulcerative colitis.
- Author
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Heuthorst L, Mookhoek A, Wildenberg ME, D'Haens GR, Bemelman WA, and Buskens CJ
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- Adult, Appendicitis pathology, Appendicitis surgery, Female, Humans, Male, Middle Aged, Prevalence, Remission Induction, Appendectomy, Appendicitis complications, Colitis, Ulcerative complications
- Abstract
Background: Previous studies have indicated that the appendix may be a priming site of ulcerative colitis (UC). Appendectomy is inversely associated with the development of UC, and is suggested to have a beneficial effect on the disease course in patients with refractory disease., Objective: The aim of the current study was to assess histological features of appendices from patients with UC and their clinical relevance., Methods: Patients with UC in remission and active UC (therapy refractory) that underwent appendectomy between 2012 and 2019 were included. Histological features of UC appendices were compared to those of patients with acute appendicitis and colon carcinoma. The Robarts Histopathology Index (RHI) was used to assess appendiceal inflammation. In patients with active UC, histological and clinical characteristics were compared between patients with and without endoscopic response following appendectomy., Results: In total, 140 appendix specimens were assessed (n = 35 UC remission, n = 35 active UC, n = 35 acute appendicitis, n = 35 colon carcinoma). Histological features of appendices from UC patients looked like UC rather than acute appendicitis. The presence of active appendiceal inflammation was comparable between patients in remission versus active disease (53.7% vs. 46.3%, p = 0.45) and limited versus extensive disease (58.5% vs. 41.5%, p = 0.50). Endoscopic response (Mayo 0-1) following appendectomy, assessed in 28 therapy refractory patients, was more frequently seen in patients with higher RHI scores (RHI > 6: 81.8% vs. RHI ≤ 6: 9.1%, p = 0.03) and limited disease (proctitis/left sided 63.6% vs. pancolitis 36.4%, p = 0.02)., Conclusion: The presence of active appendiceal inflammation is common in UC and does not correlate with colonic disease activity. More than 50% of UC patients in remission showed active histological disease in the appendix. Favorable response to appendectomy for refractory UC was seen in cases with ulcerative appendicitis. These findings might support the role of the appendix as a pivotal organ in UC., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)
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- 2021
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49. CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn's disease.
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Krabbendam L, Heesters BA, Kradolfer CMA, Haverkate NJE, Becker MAJ, Buskens CJ, Bemelman WA, Bernink JH, and Spits H
- Subjects
- Antigens, Differentiation, T-Lymphocyte genetics, Cells, Cultured, Crohn Disease genetics, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunity, Innate genetics, Immunity, Innate physiology, Inflammation immunology, Inflammation metabolism, Lymphocytes immunology, Perforin genetics, Real-Time Polymerase Chain Reaction, Antigens, Differentiation, T-Lymphocyte metabolism, Crohn Disease immunology, Crohn Disease metabolism, Interleukin-7 Receptor alpha Subunit metabolism, Lymphocytes metabolism, NK Cell Lectin-Like Receptor Subfamily D metabolism, Perforin metabolism
- Abstract
Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-β strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn's disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn's disease patients and may play a role in the pathology of the disease., (© 2021. The Author(s).)
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- 2021
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50. The importance of rectal contrast in CT assessment to detect anastomotic leakage after colorectal surgery.
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Marres CCM, Engelmann EWM, Buskens CJ, Haak HE, Bemelman WA, and van de Ven AWH
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- Anastomosis, Surgical adverse effects, Anastomotic Leak diagnostic imaging, Anastomotic Leak etiology, Humans, Rectum diagnostic imaging, Rectum surgery, Tomography, X-Ray Computed, Colorectal Surgery, Rectal Neoplasms
- Abstract
Aim: Computed tomography (CT) is currently the diagnostic tool most often used to detect anastomotic leakage (AL) after colorectal surgery. The aim of this study was to investigate the value of rectal contrast., Method: All patients who underwent colorectal surgery with a primary anastomosis between 2009 and 2018 were identified from a prospectively maintained database. Patients who underwent postoperative CT scanning in suspicion of AL were included. The clinical and radiological outcomes of patients with and without rectal contrast were compared., Results: A total of 1183 patient records were reviewed; 225 patients underwent CT-abdomen in suspicion of AL. Of these patients, 175 (77.8%) received rectal contrast. Sensitivity and specificity in this group were 78% and 94%, respectively. The positive predictive value (PPV) was 0.78 and the negative predictive value (NPV) was 0.94. In the group without rectal contrast (n = 50), sensitivity was 47%, specificity 88%, PPV 0.66 and NPV 0.76. In patients who received rectal contrast, contrast reached the anastomosis in 81.7% compared with 26.0% in patients who were given only oral contrast (p < 0.001). The sensitivity increased to 93% in the group of patients with contrast at the anastomosis, the specificity to 97%, the PPV to 0.88 and the NPV to 0.98. No adverse events were observed after the use of rectal contrast., Conclusion: The use of rectal contrast led to a significant increase in the predictive value of CT scanning for AL, especially when it reached the anastomosis. This suggests that rectal contrast is a safe and useful adjunct to CT-abdomen in the detection of AL., (© 2021 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)
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- 2021
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