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BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly. ispartof: NEUROGASTROENTEROLOGY AND MOTILITY vol:35 issue:6 ispartof: location:England status: accepted

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.

Introduction: We aimed to provide a practical and evidence-based guide on the indications, performance and reporting of high-resolution oesophageal manometry (HRM) and ambulatory pH monitoring (PHM) in adult patients in Singapore. Methods: The guideline committee comprised local gastroenterologists from public and private sectors with particular expertise in aspects of HRM and PHM, and it was tasked to produce evidence-based statements on the indications, performance and reporting of these tests. Each committee member performed literature searches to retrieve relevant articles within the context of domains to which they were assigned. Results: Twelve recommendation statements were created and summarised. Conclusion: Standardising key aspects of HRM and PHM is imperative to ensure the delivery of high-quality care. We reported the development of recommendations for the performance and interpretation of HRM and ambulatory reflux monitoring in Singapore. Keywords: Gastro-oesophageal reflux disease, GERD, high-resolution oesophageal manometry, oesophagus, pH testing

Background: Peroral endoscopic myotomy (POEM) is increasingly used as primary treatment for esophageal achalasia, in place of the options such as Heller myotomy (HM) and pneumatic dilatation (PD) Objective: These evidence-based guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) intend to support clinicians, patients and others in decisions about the use of POEM for treatment of achalasia. Results: The panel agreed on 4 recommendations for adults and children with achalasia. Conclusions: Strong recommendation for the use of POEM over PD was issued unless the concern of continued postoperative PPI use remains a key decision-making concern to the patient. Conditional recommendations included the option of using either POEM or HM with fundoplication to treat achalasia, and favored POEM over HM for achalasia subtype III.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ. © 2020 John Wiley & Sons Ltd, National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK: P01 DK092217, National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: P01 DK092217

Peroral endoscopic myotomy (POEM) is increasingly used as primary treatment for esophageal achalasia, in place of the options such as Heller myotomy (HM) and pneumatic dilatation (PD) OBJECTIVE: These evidence-based guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) intend to support clinicians, patients and others in decisions about the use of POEM for treatment of achalasia.The panel agreed on 4 recommendations for adults and children with achalasia.Strong recommendation for the use of POEM over PD was issued unless the concern of continued postoperative PPI use remains a key decision-making concern to the patient. Conditional recommendations included the option of using either POEM or HM with fundoplication to treat achalasia, and favored POEM over HM for achalasia subtype III.

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.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: in a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews., Ironwood; Shire; AllerganAllergan; TakedaTakeda Pharmaceutical Company Ltd; Fundamental Research Grant Scheme (FRGS) of the Ministry of Education of Malaysia [203.PPSP.6171192]; Takeda-Israel; Romanian Society of Neurogastroenterology, The study was funded, in part, by research grants from Ironwood, Shire, Allergan, and Takeda. The study in Malaysia was funded by the Fundamental Research Grant Scheme (FRGS) of the Ministry of Education of Malaysia (Reference: 203.PPSP.6171192). The study in Israel was funded by Takeda-Israel. The study in Romania was funded by the Romanian Society of Neurogastroenterology. None of the funders was involved in the planning, design, implementation, statistical analyses or any other aspect of the study including preparation of the paper or knowledge of its contents.

Background/Aims The prevalence of irritable bowel syndrome (IBS) has risen considerably over the past decade in Singapore. We aim to explore the contribution of changes in diet, lifestyle and habits that may contribute to the increased prevalence and development of IBS. Methods This is a survey-based cross-sectional population study aimed to gather demographic, socio-economical, lifestyle, dietary, antibiotic usage and other related information. Subjects were adult male or female Singaporeans aged 21 years or above. Association of the factors gathered with the presence or absence of IBS (by Rome III criteria) was assessed using chi-square or Fisher’s exact test. Variables with a level of statistical significance of 0.1 or less in the univariate analysis were entered into a stepwise logistic regression model. Results A total of 297 subjects participated in the study (female 60.3%). Overall, 20.9% subjects fulfilled the Rome III IBS criteria. Univariate analysis showed that IBS was associated with pet ownership, antibiotic usage, late dinner, (> 9 PM) and consumption of Western meals, coffee, and bread. The multivariate logistic regression analyses showed that IBS was independently associated with being a pet owner (P = 0.008; OR, 2.5; 95% CI, 1.278–5.037). Conclusions The prevalence of IBS was 20.9% using the Rome III criteria in our study. The association between IBS and pet ownership will need further investigation.

Background Endogenous pain modulation (EPM) is central to the processing of sensory information. Visceral and somatic EPM are abnormal in irritable bowel syndrome, but have not been studied in functional dyspepsia (FD). Methods Visceral EPM was assessed in 34 FD patients and 42 healthy controls. Gastric pain was induced with oral capsaicin and EPM was studied by adding heterotopic thermal foot stimulation or distraction by STROOP test. Somatic EPM was assessed using foot heat stimulation with heterotopic hand electrical stimulation. Key Results Endogenous pain modulation by distraction reduced mean gastric pain by 11.9 on the 0–100 visual analog scale (95% CI: 3.8–20.1) in controls (p = 0.006) and by 2.0 (−6.18 to 10.44) in FD (p = 0.6), with greater EPM in controls than in FD (difference −13.3 [−26.1 to −0.5]; p = 0.04). Endogenous pain modulation by heterotopic foot stimulation reduced gastric pain by 6.5 (−0.7 to 13.6) in controls (p = 0.07) and by 7.1 (−2.29 to 16.47) in FD (p = 0.1), with no significant difference in EPM between controls and FD (−2.0 [−14.5 to 10.5]; p = 0.75). In patients with prominent FD pain, greater pain correlated with decreased visceral EPM by distraction (r = 0.51, p = 0.04). Somatic EPM by heterotopic stimulation significantly decreased foot pain in controls (p = 0.004), but not in FD (p = 0.80). Conclusions & Inferences In FD, visceral pain modulation by distraction was dysfunctional compared to controls. Somatic pain modulation was also decreased in FD. These data and the correlation of abnormal pain modulation by distraction with clinical pain in pain-predominant FD suggest a potential pathophysiological significance of abnormal pain modulation in FD.

We present a case of massive lower gastrointestinal hemorrhage secondary to Salmonella enterica subtype Typhi (S. Typhi) colitis, in a 29 year-old female treated for S. Typhi bacteremia. One week post-treatment, she unexpectedly developed a large volume of rectal bleeding. Endoscopy showed colonic ulcers and ileitis, but no endoscopic hemostasis was required. Treatment was supportive with transfusions and a prolonged course of antimicrobials, with the bleeding stopping spontaneously. This case illustrates the phenomenon of delayed lower gastrointestinal hemorrhage, as a rare complication of S. Typhi infection.

Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum.

Caregiver burden is documented in several chronic diseases, but it has not been investigated in celiac disease (CD). We aim to quantify the burden to partners of CD patients and identify factors that affect the perceived burden. We surveyed patients with biopsy-proven CD and their partners. Patients completed CD-specific questions, including the validated Celiac Symptom Index (CSI) survey. Partners completed the validated Zarit Burden Interview (ZBI) and questions regarding sexual and relationship satisfaction. Univariable and multivariable analyses were used to assess the association between demographics, CD characteristics, and partner burden. In total, 94 patient/partner pairs were studied. Fifteen patients (16 %) reported a CSI score associated with a poor quality of life, and 34 partners (37 %) reported a ZBI score corresponding to mild-to-moderate burden. Twenty-two partners (23 %) reported moderate-to-low overall relationship satisfaction, and 12 (14 %) reported moderate-to-low sexual satisfaction. The degree of partner burden was directly correlated with patient CSI score (r = 0.27; p = 0.008), and there were moderate-to-strong inverse relationships between partners’ burden and relationship quality (r = −0.70; p

Background and Aim Chronic constipation is usually associated with young women, and urinary and sexual dysfunction has been reported as co-morbidity. Elderly men also appear to suffer from chronic constipation, as well as lower urinary tract symptoms and erectile dysfunction, but their association as co-morbidity has not been studied in the community. The aim of the present study was to determine the prevalence of bowel symptoms in our community with particular reference to the association with urinary and sexual dysfunction in the male population. Methods A population-based cross–sectional survey involving 2276 subjects (1143 male, 1133 female) representative of the Singapore population demographics was conducted to evaluate the prevalence of chronic bowel disturbances, lower urinary tract symptoms (LUTS), and erectile dysfunction (ED). Results The prevalence of chronic constipation was 25.1% overall, with the highest in men aged ≥ 70 years (35.8%) followed by women aged 20–29 years (30.5%). The commonest symptoms reported in chronic constipation were hard stool (95.1%), straining (90.9%) and incomplete evacuation (53.8%). Bloating was often experienced by 25.5% of the community, among whom 61.1% had some form of bowel disturbance. In men aged ≥ 30 years, LUTS (7.8% v 3.1%) and ED (60.5% v 48.6%) were more common in men with than without chronic constipation; constipation was an independent predictor of ED. Conclusions In this Asian urban community, chronic constipation was more common than previously suspected, and urinary and erectile dysfunction were found to be co-morbidity in men.

Background Sensory sensitization is one of the main pathophysiological hypotheses in functional gastrointestinal disorders (FGIDs). As sensitization may affect various sensory modalities, we aimed to develop a reproducible gastric pain model utilizing polymodal pathways for use in functional and other pain disorders. Methods In this double-blind, cross-over study 42 healthy subjects swallowed one capsule containing either capsaicin 0.5 mg or nocebo every 15 min until moderate pain (intensity >30 on 100 mm visual analogue scale) was attained for at least 5 min. Pain was rated every minute. Capsaicin titration was repeated thrice for reliability calculation. Key Results Moderate pain in the upper abdomen was successfully achieved in 38 of 42 subjects (90%) with capsaicin titration and in one of 42 (2%) with nocebo. The median dosage required to induce moderate pain for at least 5 min was two capsules (interquartile range 1–3) and the median gastric pain intensity was 47 (41–53). The median duration of moderate pain was 8 min (5–12). Moderate pain was successfully reproduced with capsaicin in all subjects on study days 2 and 3, with an excellent Cronbach reliability coefficient of >0.8. Conclusions & Inferences Standardized gastric pain can be conveniently achieved in a majority of healthy subjects using a simple oral capsaicin titration, with minimal adverse events. The between-test reproducibility is high and nocebo responses are negligible. This technique stimulating a multimodal physiological pathway will be useful in the investigation of sensory changes in FGIDs, including functional dyspepsia.

Background Combined esophageal high-resolution impedance manometry (HRIM) measures multiple pressures and bolus transit simultaneously, facilitating detailed assessment of esophageal motility. Currently, normative values for water-perfused HRIM systems for Chinese populations are lacking. Methods Healthy volunteers were enrolled for comprehensive anthropometric measures, blood biochemistry tests, and an HRIM study using 22 water-perfused pressure sensors and 12 impedance channels. Ten 5-mL liquid swallows of saline at 30-second intervals were conducted. The following parameters were calculated: distal contractile integral (DCI), distal latency (DL), lower esophageal sphincter (LES) basal pressure, 4-second integrated relaxation pressure (IRP-4s), and complete bolus transit percentage. Normal values were established based on the 5th and 95th percentiles. Key results All 66 participants (34 male, 32 female, aged 21-64 years) completed the study and tolerated the HRIM procedure well. The upper normal limit (95th percentile) of IRP-4 second was 20 mmHg. The 5th-95th percentile range for DCI, DL, and complete bolus transit was 99-2186 mmHg●s●cm, 6.2-11.3 second, and 50%-100%, respectively. Age was negatively correlated with DL. Females had significantly higher upper limits for IRP-4s and median DCI than males. Multivariate analyses confirmed that IRP-4s was higher in females, and that higher body mass index and waist circumference were associated with reduced DL and better bolus transit, respectively. Conclusions and inferences We established normative values for the water-perfused HRIM system for a Chinese population. Gender and anthropometric factors may affect various major HRIM parameters and should be taken into account when interpreting HRIM results in clinical practice.

Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat training and a rest period using gas chromatography-mass spectrometry. The urinary metabotype during combat training was clearly distinct from the rest period (partial least-squares discriminant analysis (PLSDA) Q(2) = 0.581), confirming the presence of a unique stress-induced metabotype. Differential metabolites related to combat stress were further uncovered, including elevated pyroglutamate and fructose, and reduced gut microbial metabolites, namely, hippurate and m-hydroxyphenylacetate (p < 0.05). The extent of pyroglutamate upregulation exhibited a positive correlation with an increase in IBS-SSS in soldiers during combat training (r = 0.5, p < 0.05). Additionally, the rise in fructose levels was positively correlated with an increase in intestinal permeability (r = 0.6, p < 0.005). In summary, protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence and severity of GI symptoms and alteration in intestinal permeability. Our study provided novel molecular insights into stress-induced GI perturbations, which could be exploited for future biomarker research or development of therapeutic strategies.

BACKGROUND The MRI scanner environment induces marked psychological effects, but specific effects on pain perception and processing are unknown and relevant to all brain imaging studies. OBJECTIVES AND METHODS We performed visceral and somatic quantitative sensory and pain testing and studied endogenous pain modulation by heterotopic stimulation outside and inside the functional MRI scanner in 11 healthy controls and 13 patients with irritable bowel syndrome. RESULTS Rectal pain intensity (VAS 0-100) during identical distension pressures increased from 39 (95% confidence interval: 35-42) outside the scanner to 53 (43-63) inside the scanner in irritable bowel syndrome, and from 42 (31-52) to 49 (39-58), respectively, in controls (ANOVA for scanner effect: p = 0.006, group effect: p = 0.92). The difference in rectal pain outside versus inside correlated significantly with stress (r = -0.76, p = 0.006), anxiety (r = -0.68, p = 0.02) and depression scores (r = -0.67, p = 0.02) in controls, but not in irritable bowel syndrome patients, who a priori had significantly higher stress and anxiety scores. ANOVA analysis showed trends for effect of the scanner environment and subject group on endogenous pain modulation (p = 0.09 and p = 0.1, respectively), but not on somatic pain (p > 0.3). CONCLUSION The scanner environment significantly increased visceral, but not somatic, pain perception in irritable bowel syndrome patients and healthy controls in a protocol specifically aimed at investigating visceral pain. Psychological factors, including anxiety and stress, are the likely underlying causes, whereas classic endogenous pain modulation pathways activated by heterotopic stimulation play a lesser role. These results are highly relevant to a wide range of imaging applications and need to be taken into account in future pain research. Further controlled studies are indicated to clarify these findings.

Introduction. Tumour cell implantation is a rare complication in patients with head and neck cancers, who have undergone percutaneous endoscopic gastrostomy (PEG) tube placement. It has not been reported in patients who underwent a PEG insertion via the radiological or introducer technique. We describe a novel case presentation of metastatic disease in a patient who underwent PEG placement via the introducer (Russell) technique which, to the best of our knowledge, has not not previously been described. Case presentation. The patient was a 37-year-old Malay woman who developed metastatic squamous cell carcinoma deposits in her stomach and liver one month after a gastrostomy tube was removed following the completion of treatment for oropharyngeal carcinoma. Conclusion. Previous authors have advocated the use of alternative PEG insertion technique apart from the ‘pull’ technique to minimise the risk of tumour implantation from head and neck cancers. Our case report suggests that this risk is not totally eliminated when the PEG tube is inserted via the introducer technique. Keyword: endoscopic gastrostomy.

Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm.

Experimental data suggest stress-related cognitive dysfunction may be associated with increased blood-brain-barrier (BBB) permeability secondary to immune activation.We investigated the relationship between prolonged and intense physical and psychological combat-training stress, immune activation and blood-brain-barrier permeability in 37 healthy male army medical rapid response troops.Soldiers during intense combat training showed greater self-reported stress, anxiety and depression levels than at rest, as assessed by specific questionnaires. S100B, a marker of BBB permeability, as well as serum cortisol, IL-6 and TNF-α concentrations, were significantly increased in soldiers during combat training compared to rest (all p0.05). Serum S100B correlated negatively with morning serum cortisol in soldiers during combat training, but not during the rest period (r=-0.387, p0.05).We conclude that combat training inducing significant levels of stress, depression and anxiety is accompanied by evidence of increased blood-brain barrier permeability and by increases in systemic pro-inflammatory mediators.

Gastrointestinal symptoms and malabsorption following fructose ingestion (fructose intolerance) are common in functional gastrointestinal disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be related an abnormality of intestinal fructose transporter proteins.To assess the expression of the main intestinal fructose transporter proteins, glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID.The expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue was investigated using real-time reverse-transcription PCR and Western immunoblotting in 11 adults with FGID and fructose intolerance ascertained by breath testing and in 15 controls.Median expression levels of GLUT5 mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13-0.21) in patients and 0.17 (IQR 0.12-0.19) in controls (p 0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.20-0.31) and 0.26 (IQR 0.19-0.31) (p 0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.52-1.68) in patients and 0.95 (IQR 0.59-1.15) in controls (p 0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06-2.14) and 1.35 (IQR 0.96-1.79) (p 0.05).Human fructose intolerance may not be associated with marked changes in GLUT5 and GLUT2 expression. Replication of these results in a larger subject group, including measures of transporter activation and membrane and subcellular localization, is warranted.

The digital rectal examination (DRE) may be underutilized. We assessed the frequency of DREs among a variety of providers and explored factors affecting its performance and utilization.A total of 652 faculty, fellows, medical residents, and final-year medical students completed a questionnaire about their use of DREs.On average, 41 DREs per year were performed. The yearly number of examinations was associated with years of experience and specialty type. Patient refusal rates were lowest among gastroenterology (GI) faculty and highest among primary-care doctors. Refusal rates were negatively correlated with comfort level of the physician in performing a DRE. More gastroenterologists used sophisticated methods to detect anorectal conditions, and gastroenterologists were more confident in diagnosing them. Confidence in making a diagnosis with a DRE was strongly associated with the number of DREs performed annually.The higher frequencies of performing a DRE, lower refusal rate, degree of comfort, diagnostic confidence, and training adequacy were directly related to level of experience with the examination. Training in DRE technique has diminished and may be lost. The DRE's role in medical school and advanced training curricula needs to be re-established.

Summary Background Gastrointestinal (GI) symptoms are common in soldiers in combat or high-pressure operational situations and often lead to compromised performance. Underlying mechanisms are unclear, but neuroendocrine dysregulation, immune activation and increased intestinal permeability may be involved in stress-related GI dysfunction. Aim To study the effects of prolonged, intense, mixed psychological and physical stress on intestinal permeability, systemic inflammatory and stress markers in soldiers during high-intensity combat-training. Methods In 37 male army medical rapid response troops, GI symptoms, stress markers, segmental intestinal permeability using the 4-sugar test (sucrose, lactulose, mannitol and sucralose) and immune activation were assessed during the 4th week of an intense combat-training and a rest period. Results Combat-training elicited higher stress, anxiety and depression scores (all P

Studies have described the burden experienced by caregivers and next of kin to patients with diseases such as cancer. However, the burden of functional gastrointestinal disorders on partners of patients has not been determined. We aimed to quantify the degree of burden to partners of patients with irritable bowel syndrome (IBS), to describe the factors that affect the burden perceived, and to identify the areas of relationship that are affected.We surveyed 152 patients diagnosed with IBS at a tertiary gastrointestinal clinic, on the basis of Rome III criteria, and their partners. Their partners completed questionnaires including the Zarit Burden Interview (ZBI), Relationship Satisfaction Scale, and questions on sexual relationships. Patients with IBS were rated for disease severity by using the Functional Bowel Disease Severity Index. We compared findings with those from 39 partners of healthy individuals (controls).There were no significant demographic differences between the partners of patients with IBS and controls; demographics had no effect on burden. Burden was significantly higher among partners of IBS patients (mean ZBI score, 22.1) than controls (mean ZBI score, 11.5) (P = .0002). The degree of burden was directly related to IBS severity (P.0001). There were inverse relationships between partners' rating of burden (ZBI) and relationship quality (R = -0.60; P.001) and sexual satisfaction (R = -0.56; P.0001). There was no difference in the Relationship Satisfaction Scale scores (4.25 vs 4.19; P = .78) or sexual relationship (6.47 vs 6.21; P = .64) between partners of IBS patients and controls, respectively.Partners of patients with IBS have a significant burden (on the basis of ZBI score), compared with partners of healthy individuals. Perceived burden increases with IBS severity and poorer sexual and relationship satisfaction.

The Rome III classification system treats functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) as distinct disorders, but this distinction appears artificial, and the same drugs are used to treat both. This study's hypothesis is that FC and IBS-C defined by Rome III are not distinct entities.In all, 1,100 adults with a primary care visit for constipation and 1,700 age- and gender-matched controls from a health maintenance organization completed surveys 12 months apart; 66.2% returned the first questionnaire. Rome III criteria identified 231 with FC and 201 with IBS-C. The second survey was completed by 195 of the FC and 141 of the IBS-C cohorts. Both surveys assessed the severity of constipation and IBS, quality of life (QOL), and psychological distress.(i) Overlap: if the Rome III requirement that patients meeting criteria for IBS cannot be diagnosed with FC is suspended, 89.5% of IBS-C cases meet criteria for FC and 43.8% of FC patients fulfill criteria for IBS-C. (ii) No qualitative differences between FC and IBS-C: 44.8% of FC patients report abdominal pain, and paradoxically IBS-C patients have more constipation symptoms than FC. (iii) Switching between diagnoses: by 12 months, 1/3 of FC transition to IBS-C and 1/3 of IBS-C change to FC.Patients identified by Rome III criteria for FC and IBS-C are not distinct groups. Revisions to the Rome III criteria, possibly including incorporation of physiological tests of transit and pelvic floor function, are needed.

G A A b st ra ct s (40-69), 2440 (62%) males, consented to participate in this study. Of these, 2166 patients who had 1stand 2nd-TCS, with removal of all adenomatous polyps were randomly assigned into two groups (1087 to two-exam and 1079 to one-exam group). The results of the noninferiority test were significant (p=0.017 in per-protocol, p=0.001 in intention-to-treat). In per-protocol analysis (701 in two-exam vs 763 in one-exam group), the IL incidences of two groups were similar (1.7% vs 2.1%). The percentage of patients with adenomas in twoexam was 50.1%, versus 37.7% in one-exam group. Among all ILs, there were 6 LGD ≥10mm, 5 HGD and 1 invasive cancer in two-exam, 9 LGD ≥10mm and 8 HGD in oneexam group, respectively. Morphologically, NP-CRNs were dominant (62%, 18/29) and most of them were classified into laterally spreading tumor non-granular (LST-NG) type; (83%, 15/18). Moreover, 7 out of 15 ILs classified into LST-NG were histologically diagnosed as HGD. Conclusions: Colonoscopy performed 3 years after endoscopic removal of all adenomatous polyps detected clinically important lesions as effectively as follow-up colonoscopy after both 1 and 3 years, being such results in accordance with those of the NPS. Two complete colonoscopies before randomization provided us a lower incidence of ILs compared with NPS data (3.3%). Further investigation will be necessary to evaluate whether the detection of NP-CRNs, especially LST-NG type determines a change in the prevention of colorectal cancer.

Purpose: Poor sleep is commonly reported by patients with IBS. When stressed prior to bedtime patients with IBS show dysregulation of the pituitary-adrenal axis during sleep. Evidence suggests the tryptophan (TRP) metabolic pathways are also altered in patients with IBS. Our purpose was to determine whether alterations in TRP metabolism may be linked to cortisol in women with and without IBS. Methods: Women, ages 18-45, (n=46 IBS [Rome III]; controls [C; n=24]) were studied in a sleep laboratory and serum samples obtained on the third night following the introduction of a social stressor (anticipation of public speaking). Samples were obtained 2 hours following sleep onset (time 1) and 1 hour prior to awakening (time 2). All subjects completed a demographic data sheet, Rome III Diagnostic Questionnaire for Functional GI Disorders, Pittsburgh Quality Sleep Index (PSQI) and 28-day symptom diaries. Serum cortisol levels were determined by ELISA and metabolite levels by targeted liquid chromatography-mass spectrometry (LC-MS). Results: More women with IBS reported symptoms of insomnia (PSQI) as compared to C group (40% versus 24%) and reduced sleep efficiency by polysomnography (p

Background Visceral hypersensitivity is one of the proposed underlying mechanisms in functional dyspepsia (FD). It is not clear whether visceral hypersensitivity in FD is a manifestation of a central sensitization also encompassing somatic sensitization. Transient receptor potential vanilloid-1 (TRPV1) pathways are involved in gastric mechanosensory physiology and the TRPV1 receptor agonist, capsaicin, has been used as a chemical stimulant. Methods In this double-blind, randomized study we evaluated both visceral and somatic sensory function in 34 FD patients and 42 healthy controls using quantitative sensory testing. Visceral pain sensitivity was assessed using a validated gastric pain model with oral capsaicin capsule titration and somatic pain sensitivity was determined by foot heat and hand electric stimulation. Key Results The median capsaicin dose required to attain moderate pain was 0.5mg in FD and 1mg in controls (P = 0.03). At these doses, mean pain intensities on a 0–100 visual analog scale were greater for FD than controls [56.9 (95% confidence intervals, 52.2–61.5) vs 45.1 (41.6–48.6), resp.] (P = 0.005). Overall, mean somatic sensory and pain thresholds were similar in FD and control groups, but in a subgroup of FD pain hypersensitivity was seen on the hand and on the foot at different stimulation thresholds. Conclusions & Inferences A majority of patients with FD have visceral chemo-hypersensitivity involving TRPV1 pathways. A substantial subgroup also has somatic hypersensitivity as evidence of central sensitization.

Results: Compared to BBDR rats (n=5), LMMP preparations from normoglycemic BBDP rats (n=8) had higher MPO levels (0.0±0.0 vs. 5.4±2.2 U/mg, p

Introduction and aims Chronic stress in animals is known to have multiple effects on GI physiology, including increased intestinal permeability (IP), altered motility and sensation. Combat training in soldiers as a real-life chronic, mixed psychological and physical stress induced increased IP and pro-inflammatory mediators, as well as GI symptoms (1). In this study we investigated the association between specific GI symptoms, segmental IP changes and stress markers in soldiers during combat training. Methods The following investigations were performed in 37 healthy male soldiers without any pre-existing GI symptoms in the 4th week of intense combat exercises and a subsequent rest period 12 days post-training: 4-sugar segmental IP test using sucrose (gastroduodenal), mannitol (M), lactulose (L) (mainly small bowel) and sucralose (whole gut) (2), serum cortisol and CRF levels, GI symptoms assessed by IBS-SSS, and stress ratings by PSS-10. Means ± SE are shown. Results Of the previously asymptomatic soldiers, 26 (70%) developed GI symptoms during combat training. Specific symptoms were abnormal bowel habits (n=13, 35%) (8 constipation, 5 alternating constipation/diarrhoea), abdominal pain/significant discomfort (n=5, 13%), or both abdominal pain/significant discomfort and abnormal bowel habits (n=8, 22%), and 14 (38%) had an IBS-SSS >75. At resting, 11 (30%) still had GI symptoms. Urinary sucrose excretion 05h was greater during combat training than at rest (1.05±0.18% vs. 0.41±0.05% of oral dose, p

Recent studies suggest that patients identified by the Rome III criteria for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) are not distinct groups (1). We have shown that patients with IBS-C exhibit no or limited 5-HT response to meal ingestion, with plasma concentrations remaining similar to those under fasting conditions (2). The aim of this study was to determine whether patients with FC show a similar 5-HT response to meal ingestion as patients with IBS-C, and to investigate any relationship to gastrointestinal transit and visceral sensitivity. Methods: 23 female IBS-C patients (aged 1950yrs;Rome III), 11 female FC patients (25-46yrs;Rome III) and 23 healthy female volunteers (HV) (20-49yrs) were recruited. Platelet depleted plasma 5-HT concentrations were measured under fasting (2hrs) and fed (4hrs) conditions. Within 2 weeks, oro-caecal (hydrogen breath test) and colonic (radio-opaque markers followed by X-ray) transit, along with rectal sensitivity (barostat) were determined. 5-HT concentration was assessed using rapid liquid chromatography tandem mass spectrometry (3). Results: Both patients with FC and IBS-C had similarly reduced 5-HT responses to meal ingestion (mean increase from fasting (SD), FC:-1.1nmol/l(±6.9),p=0.1; IBS-C:-1.9 nmol/l(±7.0),p=0.02) compared with HV (4.7nmol/ l(±9.6)), but comparable fasting baseline 5-HT concentrations (FC:34.2nmol/l(±13.2); IBSC: 27.8nmol/l(±17.3); HV:27.0nmol/l(±9.6)). Likewise, both FC and IBS-C patients had similarly reduced colonic (FC:61.6hrs(±17.9),p=0.001; IBS-C:55.6hrs(±18.5),p=0.001 v HV:34.6hrs(±17.8)) but not orocecal ((FC:321.4min(±96.6); IBS-C:311.7min(±96.6) v HV:301.8min(±87.5)) transit compared with HV. Only rectal sensitivity differed between groups, with IBS-C exhibiting lower pain thresholds (23.4mmHg (±8.3), p=0.03) but not FC (32.7mmHg(±12.2) comparedwithHV (30.7mmHg(±8.2)). Further examination revealed that although the 5-HTmeal response was similar between hyper(-0.7nmol/l(±4.9)), normo(-1.5nmol/l(±7.5)) and hypo(-4.7nmol/l(±7.8)) sensitive constipated patients, those with hypo-sensitivity (FC(27%) and IBS-C(4%)) had higher baseline fasting and fed 5-HT concentrations (fasting: 44.3nmol/l(±17.2), fed: 39.6nmol/l(±20.8), p=0.001p105:2228-2234, (2) Gastroenterol 2006;130:34-43, (3) J Chromatogr B 2009;877:2163±