Publications by authors named "Heiko De Schepper"

25 Publications

  • Page 1 of 1

Rectocele: victim of availability bias? Results of a Belgian survey of colorectal and gynecological surgeons.

Int Urogynecol J 2022 Feb 24. Epub 2022 Feb 24.

Department of Abdominal, Pediatric and Reconstructive Surgery, Antwerp University Hospital, Drie Eikenstraat 566, 2650, Edegem, Belgium.

Introduction And Hypothesis: Women with a symptomatic rectocele may undergo different trajectories depending on the specialty consulted. This survey aims to evaluate potential differences between colorectal surgeons and gynecologists concerning the management of a rectocele.

Methods: A web-based survey was sent to abdominal surgeons (CS group) and gynecologists (G group) asking about their perceived definition, diagnostic workup, multidisciplinary discussion (MDT) and surgical treatment of rectoceles. The answers of both groups were analyzed with the chi-square test or Fisher's exact test at p < 0.050.

Results: A rectocele was defined as a prolapse of the posterior vaginal wall by 78% of the G and 41% of the CS group. All gynecologists and 49% of the CS group evaluated a rectocele clinically in dorsal decubitus, with 91% of gynecologists using a speculum and 65% using the Pelvic Organ Prolapse-Quantification (POP-Q) scoring system, compared to < 1/3 of colorectal surgeons. A digital rectal examination was performed by 90% of the CS group and 57% of the G group. A transvaginal ultrasound was only used by the G group, while anal manometry was opted for by the CS group (65%) and minimally by the G group (14%). In the G group, a posterior repair was the preferred surgical technique (78%), whereas 63% of the CS group preferred a rectopexy. Multidisciplinary discussions (MDT) were mostly organized ad hoc.

Conclusions: An availability bias is seen in different aspects of rectocele evaluation and treatment. Colorectal surgeons and gynecologists are acting based on their training and experience. Motivation for pelvic floor MDT starts with creating awareness of the availability bias.
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http://dx.doi.org/10.1007/s00192-022-05118-4DOI Listing
February 2022

High-resolution colonic manometry interobserver analysis trial.

Neurogastroenterol Motil 2022 01 29;34(1):e14285. Epub 2021 Nov 29.

Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Belgium.

Introduction: Colonic high-resolution manometry (HRM) is a novel, not widely used diagnostic method used in the final workup of chronic constipation before surgery. Since its introduction, different motor patterns have been defined. However, it remains to be established whether these patterns are easily and reproducibly identified by different investigators.

Methods: The primary aim of this study was to determine agreement for motor pattern identification with HRM. To calculate the interobserver agreement (IOA), the Fleiss's kappa statistic for multiple observers was used. Seven participants analyzed 106 one-min time frames, derived from five measurements in healthy volunteers and five in patients with chronic constipation. The time frames were chosen to show a variety and combination of motor patterns consisting of short antegrade, short retrograde, cyclic anterograde, cyclic retrograde, long antegrade, long retrograde, slow retrograde motor pattern, high-amplitude propagating motor patterns, and pancolonic pressurizations. All of the measurements were performed with a solid-state colonic HRM catheter, comprising 40 pressure sensors spaced 2.5 cm apart.

Results: A median of 10.25 h (range 6-20) were required to analyze all time frames. High-amplitude propagating contractions achieved an almost perfect level of agreement (k = 0.91). Several motor patterns achieved substantial agreement; these included the short antegrade (k = 0.63), long antegrade (k = 0.68), cyclic retrograde (k = 0.70), slow retrograde motor pattern (k = 0.80), and abdominal pressure or movement artifacts (k = 0.67). Moderate agreement was found for short retrograde (k = 0.57), cyclic anterograde (k = 0.59), long retrograde motor patterns (k = 0.59) and simultaneous pressure waves (k = 0.59).

Conclusion: For the majority of motor patterns, the overall IOA for colonic manometry was substantial or high. This high level of agreement supports the use of colonic manometry application in clinical and research settings. Harmonization has the potential to improve agreement for long anterograde motor patterns with high amplitudes and for mixed direction patterns.
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http://dx.doi.org/10.1111/nmo.14285DOI Listing
January 2022

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

Neurogastroenterol Motil 2021 09;33(9):e14238

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1111/nmo.14238DOI Listing
September 2021

Local Colonic Administration of a Serine Protease Inhibitor Improves Post-Inflammatory Visceral Hypersensitivity in Rats.

Pharmaceutics 2021 May 29;13(6). Epub 2021 May 29.

Laboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, 2610 Wilrijk, Belgium.

Dysregulation of the protease-antiprotease balance in the gastrointestinal tract has been suggested as a mechanism underlying visceral hypersensitivity in conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). We aimed to study the potential therapeutic role of an intracolonically administered serine protease inhibitor for the treatment of abdominal pain in a post-inflammatory rat model for IBS. An enema containing 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce colitis in male Sprague-Dawley rats, whereas controls received a saline solution. Colonoscopies were performed to confirm colitis and follow-up mucosal healing. In the post-inflammatory phase, the serine protease inhibitor UAMC-00050 (0.1-5 mg/kg) or its vehicle alone (5% DMSO in HO) was administered in the colon. Thirty minutes later, visceral mechanosensitivity to colorectal distensions was quantified by visceromotor responses (VMRs) and local effects on colonic compliance and inflammatory parameters were assessed. Specific proteolytic activities in fecal and colonic samples were measured using fluorogenic substrates. Pharmacokinetic parameters were evaluated using bioanalytical measurements with liquid chromatography-tandem mass spectrometry. Post-inflammatory rats had increased trypsin-like activity in colonic tissue and elevated elastase-like activity in fecal samples compared to controls. Treatment with UAMC-00050 decreased trypsin-like activity in colonic tissue of post-colitis animals. Pharmacokinetic experiments revealed that UAMC-00050 acted locally, being taken up in the bloodstream only minimally after administration. Local administration of UAMC-00050 normalized visceral hypersensitivity. These results support the role of serine proteases in the pathophysiology of visceral pain and the potential of locally administered serine protease inhibitors as clinically relevant therapeutics for the treatment of IBS patients with abdominal pain.
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http://dx.doi.org/10.3390/pharmaceutics13060811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229129PMC
May 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

United European Gastroenterol J 2021 04;9(3):307-331

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1002/ueg2.12061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259261PMC
April 2021

Biopsy Sampling in Upper Gastrointestinal Endoscopy: A Survey from 10 Tertiary Referral Centres Across Europe.

Dig Dis 2021 1;39(3):179-189. Epub 2020 Oct 1.

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: Guidelines give robust recommendations on which biopsies should be taken when there is endoscopic suggestion of gastric inflammation. Adherence to these guidelines often seems arbitrary. This study aimed to give an overview on current practice in tertiary referral centres across Europe.

Methods: Data were collected at 10 tertiary referral centres. Demographic data, the indication for each procedure, endoscopic findings, and the number and sampling site of biopsies were recorded. Findings were compared between centres, and factors influencing the decision to take biopsies were explored.

Results: Biopsies were taken in 56.6% of 9,425 procedures, with significant variation between centres (p < 0.001). Gastric biopsies were taken in 43.8% of all procedures. Sampling location varied with the procedure indication (p < 0.001) without consistent pattern across the centres. Fewer biopsies were taken in centres which routinely applied the updated Sydney classification for gastritis assessment (46.0%), compared to centres where this was done only upon request (75.3%, p < 0.001). This was the same for centres stratifying patients according to the OLGA system (51.8 vs. 73.0%, p < 0.001). More biopsies were taken in centres following the MAPS guidelines on stomach surveillance (68.1 vs. 37.1%, p < 0.001). Biopsy sampling was more likely in younger patients in 8 centres (p < 0.05), but this was not true for the whole cohort (p = 0.537). The percentage of procedures with biopsies correlated directly with additional costs charged in case of biopsies (r = 0.709, p = 0.022).

Conclusion: Adherence to guideline recommendations for biopsy sampling at gastroscopy was inconsistent across the participating centres. Our data suggest that centre-specific policies are applied instead.
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http://dx.doi.org/10.1159/000511867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220928PMC
May 2021

Volatomics in inflammatory bowel disease and irritable bowel syndrome.

EBioMedicine 2020 Apr 21;54:102725. Epub 2020 Apr 21.

Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium; Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium. Electronic address:

Volatile organic compounds (VOCs) are produced by the human metabolism, inflammation and gut microbiota and form the basis of innovative volatomics research. VOCs detected through breath and faecal analysis hence serve as attractive, non-invasive biomarkers for diagnosing and monitoring irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This review describes the clinical applicability of volatomics in discriminating between IBS, IBD and healthy volunteers with acceptable accuracy in breath (70%-100%) and faecal (58%-85%) samples. Promising compounds are propan-1-ol for diagnosing and monitoring of IBD patients, and 1-methyl-4-propan-2-ylcyclohexa-1,4-diene as biomarker for IBS diagnosis. However, these VOCs often seem to be related to inflammation and probably will need to be used in conjunction with other clinical evidence. Furthermore, three interventional studies underlined the potential of VOCs in predicting treatment outcome and patient follow-up. This shows great promise for future use of VOCs as non-invasive breath and faecal biomarkers in personalised medicine. However, properly designed studies that correlate VOCs to IBD/IBS pathogenesis, while taking microbial influences into account, are still key before clinical implementation can be expected.
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http://dx.doi.org/10.1016/j.ebiom.2020.102725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177032PMC
April 2020

In-Depth Study of Transmembrane Mucins in Association with Intestinal Barrier Dysfunction During the Course of T Cell Transfer and DSS-Induced Colitis.

J Crohns Colitis 2020 Jul;14(7):974-994

Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.

Background And Aims: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis.

Methods: We quantified 4-kDa FITC-dextran intestinal permeability and the expression of cytokines, mucins, junctional and polarity proteins at dedicated time points in the adoptive T cell transfer and dextran sodium sulfate [DSS]-induced colitis models. Mucin expression was also validated in biopsies from IBD patients.

Results: In both animal models, the course of colitis was associated with increased interleukin-1β [IL-1β] and tumour necrosis factor-α [TNF-α] expression and increased Muc1 and Muc13 expression. In the T cell transfer model, a gradually increasing Muc1 expression coincided with gradually increasing 4-kDa FITC-dextran intestinal permeability and correlated with enhanced IL-1β expression. In the DSS model, Muc13 expression coincided with rapidly increased 4-kDa FITC-dextran intestinal permeability and correlated with TNF-α and Muc1 overexpression. Moreover, a significant association was observed between Muc1, Cldn1, Ocln, Par3 and aPKCζ expression in the T cell transfer model and between Muc13, Cldn1, Jam2, Tjp2, aPkcζ, Crb3 and Scrib expression in the DSS model. Additionally, MUC1 and MUC13 expression was upregulated in inflamed mucosa of IBD patients.

Conclusions: Aberrantly expressed MUC1 and MUC13 might be involved in intestinal barrier dysfunction upon inflammation by affecting junctional and cell polarity proteins, indicating their potential as therapeutic targets in IBD.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa015DOI Listing
July 2020

Hemorrhoidal disease and chronic venous insufficiency: Concomitance or coincidence; results of the CHORUS study (Chronic venous and HemORrhoidal diseases evalUation and Scientific research).

J Gastroenterol Hepatol 2020 Apr 30;35(4):577-585. Epub 2019 Oct 30.

Department of Gastroenterology and Hepatology, University Hospital Antwerp, Edegem, Belgium.

Background And Aim: The CHORUS study (Chronic venous and HemORrhoidal diseases evalUation and Scientific research) was conducted to provide data on patients presenting with hemorrhoidal disease (HD) in clinical practice and to explore the frequency with which it coexists with chronic venous disease (CVD) and shared risk factors.

Methods: This international, noninterventional study enrolled adult patients attending a consultation for hemorrhoidal complaints. The questionnaire completed by physicians established the subjects' demographic and lifestyle characteristics and collected information on HD grade and symptoms and signs of CVD.

Results: A total of 5617 patients were analyzed. Symptoms commonly reported were bleeding (71.8%), pain (67.4%), swelling (55.0%), itching (44.1%), and prolapse (36.2%). Multivariate analysis revealed the variables with the strongest association with HD severity were older age, higher CVD CEAP (Clinical manifestations, Etiologic factors, Anatomic distribution of disease, and underlying Pathophysiology) class, constipation, and male gender (all P < 0.0001). Elevated BMI was a risk factor for HD recurrence. Among women, number of births had a significant association with both HD grade and recurrence. The presence of CVD, reported in approximately half the patients (51.2%), was strongly associated with advanced grade of HD (P < 0.0001). Treatments most commonly prescribed were venoactive drugs (94.3%), dietary fiber (71.4%), topical treatment (70.3%), analgesics (26.3%), and surgery (23.5%).

Conclusions: CHORUS provides a snap shot of current profiles, risk factors, and treatments of patients with HD across the globe. The coexistence of HD and CVD in more than half the study population highlights the importance of examining for CVD among patients with a hemorrhoid diagnosis, particularly when shared risk factors are present.
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http://dx.doi.org/10.1111/jgh.14857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187474PMC
April 2020

Next generation of biologics for the treatment of Crohn's disease: an evidence-based review on ustekinumab.

Clin Exp Gastroenterol 2017 15;10:293-301. Epub 2017 Nov 15.

Department of Gastroenterology, Universitair Ziekenhuis Antwerpen, University of Antwerp, Antwerp, Belgium.

The limited efficacy of the currently available medical therapies in a proportion of patients with Crohn's disease has led to the research and development of molecules that can block new inflammatory pathways. Ustekinumab is a fully human IgG1 monoclonal antibody which targets the common p40 subunit of the cytokines interleukin-12 as well as interleukin-23. Consequently, the Th1 and Th17 inflammatory responses are inhibited. Ustekinumab has been recently approved for its use in patients with Crohn's disease. Its efficacy and safety was initially proved in patients with psoriasis and psoriatic arthritis. More recently, three Phase III trials have confirmed its efficacy in patients with Crohn's disease refractory to anti-tumor necrosis factor therapy. This biologic agent appears safe, with no increased risk of infectious or malignant complications, and a low immunogenic profile.
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http://dx.doi.org/10.2147/CEG.S110546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697448PMC
November 2017

Colonoscopy in patients with liver cirrhosis : success and safety issues.

Acta Gastroenterol Belg 2015 Dec;78(4):411-4

Background: Patients with liver cirrhosis undergo screening colonoscopy before liver transplantation. Screening colonoscopy is subject to specific quality criteria, among which caecal intubation rate. Several factors associated with failed caecal intubation have been identified.

Aims: We investigated whether liver cirrhosis influenced success and safety of screening colonoscopy.

Methods: Caecal intubation and complication rate of 93 candidates for liver transplantation due to liver cirrhosis were compared with the control rates of our endoscopy unit. Several patient and colonoscopy variables were taken into account.

Results: In patients with liver cirrhosis caecal intubation rate was only 83%, whereas in the control group it was 94% (P<0.0001). The presence of high volume ascites tends to compromise a successful colonoscopy. Serious complication rate was 0,4% in controls without colonoscopy-related mortality. In the cirrhotic population two severe complications were encountered (2,2%, P<0.05) and one patient died due to colonic perforation and sepsis (mortality 1.1%).

Conclusions: Caecal intubation rate is significantly lower in patients with liver cirrhosis undergoing screening colonoscopy, possibly related to the presence of ascites. Complication and mortality rate of screening colonoscopy is significantly higher in patients being screened for liver transplantation.
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December 2015

Effects of antidepressants in patients with functional esophageal disorders or gastroesophageal reflux disease: a systematic review.

Clin Gastroenterol Hepatol 2015 Feb 3;13(2):251-259.e1. Epub 2014 Jul 3.

Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address:

Background & Aims: Patients with functional esophageal disorders present with symptoms of chest pain, heartburn, dysphagia, or globus in the absence of any structural abnormality. Visceral hypersensitivity is a feature of these functional disorders, and might be modulated by antidepressant therapy. We evaluated evidence for the efficacy of antidepressant therapy for symptoms associated with esophageal visceral hypersensitivity in patients with functional esophageal disorders or gastroesophageal reflux disease (GERD).

Methods: We performed a systematic search of the Cochrane Comprehensive Trial Register, MEDLINE, and EMBASE (through February 2014). We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy on experimentally induced esophageal sensation or intensity, or frequency of heartburn, chest pain, dysphagia, or globus.

Results: The search strategy identified 378 articles; 15 described randomized controlled trials that were eligible for inclusion. In addition, 1 conference abstract and 2 case reports were included, providing the best available evidence on specific symptoms. Esophageal pain thresholds increased by 7% to 37% after antidepressant therapy. Antidepressant therapy reduced functional chest pain over a range from 18% to 67% and reduced heartburn in patients with GERD over a range of 23% to 61%. One study included patients with globus and none of the studies included patients with functional heartburn or functional dysphagia.

Conclusions: Based on a systematic review, antidepressants modulate esophageal sensation and reduce functional chest pain. There is limited evidence that antidepressants benefit a subgroup of patients with GERD. More controlled trials are needed to investigate the effects of antidepressants on functional esophageal disorders.
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http://dx.doi.org/10.1016/j.cgh.2014.06.025DOI Listing
February 2015

Vocal cord paralysis due to self-expandable metal stent in the proximal esophagus.

Endoscopy 2014 22;46 Suppl 1 UCTN:E155-6. Epub 2014 Apr 22.

Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.

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http://dx.doi.org/10.1055/s-0034-1364954DOI Listing
November 2014

Distal esophageal spasm evolving to achalasia in high resolution.

Clin Gastroenterol Hepatol 2014 Feb 29;12(2):A25-6. Epub 2013 Aug 29.

Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.cgh.2013.08.035DOI Listing
February 2014

Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis: first case.

World J Gastroenterol 2013 Mar;19(10):1661-4

Department of Gastroenterology and Hepatology, Antwerp University Hospital, B-2650 Edegem-Antwerp, Belgium.

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting. Based on wireless video capsule findings he was previously diagnosed with ileal Crohn's disease at a different institution, although the clinical and radiological picture was not typical and the response to corticosteroids was poor. We performed a single-balloon enteroscopy showing a short, ulcerous stenosis 50 cm proximal from Bauhin's valve. The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). High dose corticosteroids were again started, without effect. The monoclonal tumor necrosis factor-α (TNF-α) antibody infliximab was added to the medical therapy. After induction therapy, both clinical and endoscopic amelioration was obtained. Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.
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http://dx.doi.org/10.3748/wjg.v19.i10.1661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602486PMC
March 2013

[Chronic constipation and rectal functional investigations].

Ned Tijdschr Geneeskd 2013 ;157(8):A5976

Academisch Medisch Centrum, afd. Maag-, Darm- en Leverziekten, Amsterdam, the Netherlands.

Chronic constipation is caused by disordered colonic motility, impaired rectal evacuation (dyschezia) or a combination of the two. It is important to distinguish the predominant mechanism of constipation in order to choose the optimal therapy (laxatives or prokinetics versus pelvic floor retraining or surgery). The contribution of dyschezia to constipation can usually be identified by a digital rectal examination, but should, in our opinion, be confirmed by anal manometry, transrectal ultrasonography or defecography. These diagnostic methods provide additional information on the severity of the rectal outlet obstruction, the contribution of rectal hyposensitivity and the presence of potentially correctable anomalies such as a rectocele, enterocele or rectoanal intussusception. We conclude that clinical anorectal examination and functional studies are both necessary and complementary to each other in the evaluation and management of patients with chronic constipation who do not respond to standard laxative treatment.
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April 2013

An unusual cause of Dysphagia.

Clin Gastroenterol Hepatol 2013 Sep 13;11(9):A20. Epub 2012 Dec 13.

Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.cgh.2012.12.002DOI Listing
September 2013

Role of TRPV1 and TRPA1 in visceral hypersensitivity to colorectal distension during experimental colitis in rats.

Eur J Pharmacol 2013 Jan 23;698(1-3):404-12. Epub 2012 Oct 23.

Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

The aim of the present study is to investigate the effects of TRPV1 and TRPA1 receptor antagonists and their synergism on the visceromotor responses during experimental colitis in rats. Colitis was induced in rats by a TNBS/ethanol enema at day 0 and was assessed at day 3 using endoscopy, histology and a myeloperoxidase assay. The visceromotor response to colorectal distension (10-80 mmHg) was evaluated in conscious rats before (control condition) and 3 days after 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration (colitis condition). At day 3, visceromotor responses were assessed before and after treatment with a TRPV1 (BCTC) or TRPA1 (TCS-5861528) receptor antagonist either alone or in combination and either after intraperitoneal or intrathecal administration. Endoscopy, microscopy and myeloperoxidase activity indicated severe colonic tissue damage 3 days after TNBS administration. Colorectal distension-evoked visceromotor responses demonstrated a 2.9-fold increase during acute colitis (day 3) compared to control conditions. Intraperitoneal and intrathecal administration of BCTC or TCS-5861528 partially reversed the colitis-induced increase in visceromotor responses compared to control conditions (P<0.05). Intraperitoneal blockade of TRPA1 plus TRPV1 further decreased the enhanced visceromotor responses at high distension pressures (40-80 mmHg) compared to blockade of either TRPV1 or TRPA1 alone. This synergistic effect was not seen after combined intrathecal blockade of TRPA1 plus TRPV1. The present study demonstrates that in the rat, TRPV1 and TRPA1 play a pivotal role in visceral hypersensitivity at the peripheral and spinal cord level during acute TNBS colitis. Target interaction, however, is presumably mediated via a peripheral site of action.
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http://dx.doi.org/10.1016/j.ejphar.2012.10.014DOI Listing
January 2013

MUTYH associated polyposis coli: one common and one rare mutation.

Dig Dis Sci 2012 Jul 9;57(7):1968-70. Epub 2012 Mar 9.

Division of Gastroenterology, St-Vincentius Hospital, Antwerp, Belgium.

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http://dx.doi.org/10.1007/s10620-012-2107-6DOI Listing
July 2012

Involvement of afferent neurons in the pathogenesis of endotoxin-induced ileus in mice: role of CGRP and TRPV1 receptors.

Eur J Pharmacol 2009 Aug 13;615(1-3):177-84. Epub 2009 May 13.

Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Belgium.

Activation of neuronal reflex pathways by inflammatory mediators is postulated as an important pathogenic mechanism in postoperative ileus. In this study, we investigated the involvement of afferent neurons and more specifically the role of the transient receptor potential vanilloid receptor type 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in endotoxin-induced motility disturbances in mice. Mice were injected with either lipopolysaccharides (LPS) or saline (control) and pre-treated with hexamethonium (blocker of neuronal transmission), capsaicin (neurotoxin), CGRP 8-37 (CGRP antagonist) or BCTC (TRPV1 receptor antagonist). We measured gastric emptying and intestinal transit of Evans blue next to rectal temperature and a global sickness behaviour scale. In vehicle-treated mice, LPS significantly delayed gastric emptying, small intestinal transit and rectal temperature while the sickness behaviour scale was increased. Hexamethonium, capsaicin, CGRP8-37 and BCTC all reversed the endotoxin-induced delay in gastric emptying and significantly reduced the delay in intestinal transit without effect on the endotoxin-induced decrease in rectal temperature and increase in sickness behaviour scale. Our findings provide evidence for the involvement of afferent nerves in the pathogenesis of endotoxin-induced motility disturbances in mice mediated via CGRP and TRPV1 receptors. Blockade of CGRP and TRPV1 receptors may offer a novel strategy for the treatment of endotoxin-induced ileus.
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http://dx.doi.org/10.1016/j.ejphar.2009.04.055DOI Listing
August 2009

Medical presentation of constipation from childhood to early adulthood: a population-based cohort study.

Clin Gastroenterol Hepatol 2007 Sep 13;5(9):1059-64. Epub 2007 Jul 13.

University of North Carolina Center for Functional GI and Motility Disorders, Division of Pediatric Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

Background & Aims: Constipation is a common disorder in children and adults, but the role of gender and early life risk factors remains undefined. The aims of the study were as follows: (1) to estimate the incidence of medical presentation for constipation in a population-based birth cohort, and (2) to examine factors associated with constipation presentation from childhood to adulthood.

Methods: A birth cohort of all children born between 1976 and 1982 to mothers who were residents of Rochester, Minnesota, and who remained in the community until age 5 was used for this study. Medical visits for constipation were identified by diagnoses codes and chart review. Subjects were followed up based on their diagnoses accumulated while younger than 21 years old, and 80% of subjects remained in the area until 18 years of age.

Results: Of 5299 birth cohort members without constipation presentation before age 5, the overall age- and sex-adjusted incidence was 3.9 per 1000 person-years. A higher incidence for constipation in females occurred beginning at 13 years to early adulthood (rate ratio, 2.6 for 13-16 y and 4.2 for 17 to <21 y). Children with a diagnosis for constipation at younger than 5 years of age had a significantly higher incidence for subsequent medical visits for constipation through adolescence and early adulthood compared with the incidence rate of children without an early medical presentation (rate ratio, 4.5 for 5-8 y, 2.5 for 9-12 y, and 3.9 for 17-20 y).

Conclusions: Early medical presentation and female sex influence incident and repeat medical visits for constipation from childhood to early adulthood.
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http://dx.doi.org/10.1016/j.cgh.2007.04.028DOI Listing
September 2007

Incidence of presentation of common functional gastrointestinal disorders in children from birth to 5 years: a cohort study.

Clin Gastroenterol Hepatol 2007 Feb 8;5(2):186-91. Epub 2006 Aug 8.

Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, Minnesota 55905, USA.

Background & Aims: Gastroesophageal reflux disease (GERD), abdominal pain of unknown origin, and constipation are thought to be causes for frequent medical visits during childhood. The aim of this study was to estimate the incidences, repeat presentation, clinical symptoms, and sociodemographic risk factors in children who medically presented for GERD, abdominal pain of unknown origin, and constipation from birth to 5 years.

Methods: This was a population-based, retrospective birth cohort study of all children born to mothers residing in Rochester, Minnesota who remained in the area until at least age 5 (n = 5718). The medical records of all individuals were searched for relevant diagnostic billing codes for GERD, abdominal pain of unknown origin, and constipation, without another underlying diagnosis, and manually reviewed. Parental sociodemographic factors collected from birth certificate records on patients and matched controls were compared.

Results: The incidence for childhood (age, <5 y) presentation of GERD, abdominal pain of unknown origin, and constipation was .9/1000 person-years, 4.5/1000 person-years, and 6.8/1000 person-years, respectively; there were no significant differences between boys and girls. Three or more medical visits by age 5 occurred in 11%, 19%, and 24% of children who were seen for abdominal pain of unknown origin, constipation, and GERD, respectively. Single parentage, maternal age (<18 y), and maternal education (
Conclusions: The incidences of presentation for GERD, abdominal pain of unknown origin, and constipation are among the highest for pediatric disorders, and a cause for repeated medical consultations.
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http://dx.doi.org/10.1016/j.cgh.2006.06.012DOI Listing
February 2007

The role of tachykinins in circular muscle contractility of the murine ileum: a functional investigation.

Auton Neurosci 2006 Jun 29;126-127:273-6. Epub 2006 Mar 29.

Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.

We investigated the participation of different tachykinin receptors in contractility of circular muscle strips of the mouse ileum using selective NK receptor agonists and antagonists. The NK1 receptor agonist septide (1-100 nM) induced dose-dependent contractions which were reduced by atropine and augmented by L-NNA. L-NNA increased and TTX consecutively reduced contractions to the NK2 receptor agonist beta-A-NKA (1-100 nM). Senktide, agonist of NK3 receptors, failed to induce contractions. NANC contractions to EFS were decreased after NK1 receptor blockade with RP67580. This inhibitory effect was more pronounced after additional blockade of NK2 and NK3 receptors. NK3 receptor antagonism alone reduced contractions at higher frequencies of stimulation. When the duration of the EFS stimulus was increased, the participation of all NK receptor subtypes became more evident. Our results suggest that excitatory NANC transmission in the circular muscle layer of the mouse ileum is mediated by tachykinins acting principally on NK1 receptors on cholinergic nerves and smooth muscle cells. Also NK2 receptors, located on smooth muscle cells and nitrergic neurons, and NK3 receptors on enteric neurons are involved.
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http://dx.doi.org/10.1016/j.autneu.2006.01.018DOI Listing
June 2006

Functional characterisation of tachykinin receptors in the circular muscle layer of the mouse ileum.

Regul Pept 2005 Sep;130(3):105-15

Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.

Objectives: Tachykinins are important mediators in neuromuscular signalling but have not been thoroughly characterised in the mouse gut. We investigated the participation of tachykinin receptors in contractility of circular muscle strips of the mouse ileum.

Results: Electrical field stimulation (EFS) of excitatory nonadrenergic noncholinergic (NANC) nerves induced frequency-dependent contractions which were mimicked by substance P (SP). Desensitisation of SP and NK(1), NK(2) or NK(3) receptors significantly reduced contractions to EFS. The NK(1) receptor blocker RP67580 significantly inhibited NANC contractions to EFS. The NK(2) and NK(3) receptor blockers nepadutant and SR142801 did not affect NANC contractions per se but increased the RP67580-induced inhibition of NANC contractions to EFS. Contractions to SP were significantly reduced by RP67580 but not affected by nepadutant or SR142801. The NK(1) and NK(2) receptor agonists, septide and [beta-ala(8)]-NKA 4-10 (beta-A-NKA), respectively, but not the NK(3) receptor agonist senktide-induced dose-dependent contractions. Atropine inhibited and l-NNA augmented contractions to septide. Contractions to beta-A-NKA were insensitive to atropine but augmented by l-NNA.

Conclusions: Tachykinins mediate NANC contractions to EFS in the mouse small intestine. Endogenously released tachykinins activate mainly NK(1) receptors, located on cholinergic nerves and smooth muscle cells and, to a lesser degree, NK(2) and NK(3) receptors, most likely located presynaptically.
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http://dx.doi.org/10.1016/j.regpep.2005.04.003DOI Listing
September 2005

Functional evidence that ATP or a related purine is an inhibitory NANC neurotransmitter in the mouse jejunum: study on the identity of P2X and P2Y purinoceptors involved.

Br J Pharmacol 2003 Nov 6;140(6):1108-16. Epub 2003 Oct 6.

Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.

1. Conflicting views exist on whether ATP is a neurotransmitter in the enteric nervous system. We investigated the role of ATP in enteric transmission in circular muscle strips of the mouse jejunum. 2. On PGF2alpha-precontracted muscle strips and in the presence of atropine and guanethidine, electrical field stimulation (EFS, 1-8 Hz) of nonadrenergic noncholinergic (NANC) nerves induced transient relaxations that were abolished by the nerve-conductance blocker tetrodotoxin. The NO synthase blocker l-nitroarginine (l-NOARG) partially inhibited the NANC relaxations to EFS, but fast-twitch relaxations to EFS were still observed in the presence of l-NOARG. 3. In the presence of l-NOARG, ATP, the P2X receptor agonist alphabetaMeATP and the P2Y receptor agonist ADPbetaS relaxed jejunal muscle strips. Tetrodotoxin did not affect the relaxation to ATP and ADPbetaS, but inhibited that to alphabetaMeATP. 4. The l-NOARG-resistant NANC relaxations to EFS were almost abolished by apamin, a blocker of small-conductance Ca2+ activated K+ channels, and by suramin and PPADS, blockers of P2 purinoceptors. Relaxations to ATP were almost abolished by apamin and suramin but not affected by PPADS. 5. Desensitisation of alphabetaMeATP-sensitive P2X receptors, the P2X receptor blocker Evans blue and the P2X1,2,3 receptor blocker NF 279 inhibited the l-NOARG-resistant NANC relaxations to EFS and that to alphabetaMeATP without affecting the relaxation to ADPbetaS. Brilliant blue G, a P2X2,5,7 receptor blocker, did not affect the relaxations to EFS. 6. Desensitisation of P2Y receptors and MRS 2179, a P2Y1 receptor blocker, virtually abolished the l-NOARG-resistant NANC relaxations to EFS and the relaxation to ADPbetaS without affecting the relaxation to alphabetaMeATP. 7. Dipyridamole, an adenosine uptake inhibitor, or theophylline and 8-phenyltheophylline, blockers of P1 and A1 purinoceptors, respectively, did not affect the purinergic NANC relaxations to EFS. 8. Our results suggest that ATP or a related purine acts as an inhibitory NANC neurotransmitter in the mouse jejunum, activating P2 but not P1 purinoceptors. Relaxations to the purinergic NANC neurotransmitter mainly involve P2Y receptors of the P2Y1 subtype that are located postjunctionally. Purinergic NANC neurotransmission also involves P2X receptors, most likely of the P2X1 and P2X3 subtype, located pre- and/or postjunctionally.
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http://dx.doi.org/10.1038/sj.bjp.0705536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574122PMC
November 2003
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