Background
This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function ...testing including anorectal manometry (focused on high‐resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed.
Methods
Twenty‐nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face‐to‐face and three remote meetings to derive consensus between 2014 and 2018.
Key recommendations
The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.
Conclusions and Inferences
This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much‐needed standardization to these techniques.
This document summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance of anorectal function testing and introduces a consensus classification for disorders of anorectal function based on objective, physiological measurement.
The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy ...supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC).
Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis.
Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin-the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants.
Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to characterise IBS.
Frau Anita B., 51 Jahre, stellt sich bei ihrem Hausarzt vor, weil sich ihre seit Jahren bekannte Verstopfung seit zwei bis drei Wochen verschlechtert hat. Obwohl sie alle Empfehlungen ihres ...Hausarztes umgesetzt hat, verspürt sie keine Besserung.
To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer.
A total of 78 men who had undergone definitive CRT ...for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires.
The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecation pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for ≤1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas.
Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long-term late radiation-related intestinal toxicity was low.
Background
Ano‐rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international ...guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM between institutions to establish the status of current practice.
Methods
A 50‐item web‐based questionnaire assessing analysis and interpretation of ARM was distributed by the International Anorectal Physiology Working Group via societies representing practitioners that perform ARM. Study methodology and performance characteristics between institutions were compared.
Key Results
One hundred and seven complete responses were included from 30 countries. Seventy‐nine (74%) institutions performed at least two studies per week. Forty‐nine centers (47%) applied conventional ARM (≤8 pressure sensors) and 57 (53%) high‐resolution ARM (HR‐ARM). Specialist centers were most likely to use HR‐ARM compared to regional hospitals and office‐based practice (63% vs 37%). Most conventional ARM systems used water‐perfused technology (34/49); solid‐state hardware was more frequently used in centers performing HR‐ARM (44/57). All centers evaluated rest and squeeze. There was marked variation in the methods used to report results of maneuvers. No two centers had identical protocols for patient preparation, setup, study, and data interpretation, and no center fully complied with published guidelines.
Conclusions & Inferences
There is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co‐operation to standardize ARM.
This survey shows that there is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co‐operation to standardize ARM.
BACKGROUNDSingle-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations ...exist in irritable bowel syndrome (IBS). AIMTo assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODSIn this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTSDepressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSIONWe have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
Objective: Bacterial translocation, causing intestinal inflammation, is one of the key mechanisms in the pathogenesis of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP) The ...presence of fecal calprotectin quantitatively relates to intestinal neutrophil migration and is therefore considered as a marker of intestinal inflammation. We aimed to assess the role of fecal calprotectin concentrations (FCCs) in diagnosing the onset and severity of HE and SBP.
Methods: Sixty‐one cirrhotics were prospectively included. Forty‐two subjects served as controls. Several complications of cirrhosis were diagnosed by reference methods. Stool samples were collected for measuring FCCs. Patients revealing other causes of abnormal calprotectin results, e.g. gastrointestinal bleeding or inflammatory bowel disease were excluded. Multivariate analysis of cirrhosis‐associated complications and their relation to FCCs was performed.
Results: Fecal calprotectin concentrations were higher in cirrhotics compared with controls (P<0.001). Among cirrhotics, FCCs were elevated dependent on the severity of liver disease as assessed by Child‐ and model for end‐stage liver disease‐scores. The corresponding correlation co‐efficients by Spearman's were 0.577 (P<0.001) and 0.303 (P=0.018) respectively. A correlation emerged between elevated FCCs and HE grading as measured by West–Haven criteria and critical flicker frequency (both P<0.001; sensitivity=0.94 and 0.93, specificity=0.95 and 0.89 respectively) and SBP (P<0.02; sensitivity=0.71, specificity=0.79). FCCs were higher in cirrhotic subjects with additional extra‐intestinal inflammation (P<0.01; sensitivity=0.65, specificity=0.8). The Pearsons correlation coefficients were 0.190 and 0.164 revealing no influence (P=0.142 and P=0.207) of laboratory parameters of systemic inflammation on FCCs in cirrhotic subgroup.
Conclusions: Fecal calprotectin concentrations serve as a screening tool for HE and SBP. Assessment of FCCs may faciliate grading of HE‐severity.
Irritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS ...pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
Background
Several patients in gastroenterology practice present with esophageal symptoms, and in case of normal endoscopy with biopsies, high‐resolution manometry (HRM) is often the next step. Our ...aim was to develop a European consensus on the clinical application of esophageal HRM, to offer the clinician guidance in selecting patients for HRM and using its results to optimize clinical outcome.
Methods
A Delphi consensus was initiated with 38 multidisciplinary experts from 16 European countries who conducted a literature summary and voting process on 71 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 statements.
Results
The process generated guidance on when to consider esophageal HRM, how to perform it, and how to generate the report. The Delphi process also identified several areas of uncertainty, such as the choice of catheters, the duration of fasting and the position in which HRM is performed, but recommended to perform at least 10 5‐ml swallows in supine position for each study. Postprandial combined HRM impedance is considered useful for diagnosing rumination. There is a large lack of consensus on treatment implications of HRM findings, which is probably the single area requiring future targeted research.
Conclusions and inferences
A multinational and multidisciplinary group of European experts summarized the current state of consensus on technical aspects, indications, performance, analysis, diagnosis, and therapeutic implications of esophageal HRM.
Statements and their endorsement in the European Society for Neurogastroenterology and Motility Recommendations for the use of high‐resolution manometry of the esophagus.
Summary
Background
As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better.
Aim
To establish ...the definition of failure of a treatment to provide adequate relief (F‐PAR) to support this management and referral process in patients with chronic constipation.
Methods
We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms.
Results
The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom‐severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed).
Conclusions
We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.
PDF
