The multitarget faecal immunochemical test for improving stool-based colorectal cancer screening programmes: a Dutch population-based, paired-design, intervention study.

BACKGROUND: The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. METHODS: Individuals aged 55-75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 µg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov, NCT05314309, and is complete. FINDINGS: Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62-9·61) positivity rate and 2·27% (95% CI 2·02-2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75-4·43) and a detection rate of 1·21% (1·03-1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13-0·29) versus 0·17% (0·11-0·27) for colorectal cancer; 1·64% (1·43-1·87) versus 0·86% (0·72-1·04) for advanced adenoma, and 0·43% (0·33-0·56) versus 0·17% (0·11-0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. INTERPRETATION: The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. FUNDING: Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland.

Deworming and micronutrient status by community open defecation prevalence: An observational study using nationally representative data from India, 2016-2018.

BACKGROUND: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. METHODS AND FINDINGS: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. CONCLUSIONS: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study.

Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation.

BACKGROUND & AIMS: Despite therapeutic advances, effective treatments for chronic constipation remain an unmet need. The vibrating capsule is a nonpharmacologic, orally ingested, programmable capsule that vibrates intraluminally to induce bowel movements. We aimed to determine the efficacy and safety of the vibrating capsule in patients with chronic constipation. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial of patients with chronic constipation, who were randomized to receive either a vibrating or placebo capsule, once daily, 5 days a week for 8 weeks. The primary efficacy end points were an increase of 1 or more complete spontaneous bowel movements per week (CSBM1 responder) or 2 or more CSBMs per week (CSBM2) from baseline during at least 6 of the 8 weeks. Safety analyses were performed. RESULTS: Among 904 patients screened, 312 were enrolled. A greater percentage of patients receiving the vibrating capsule achieved both primary efficacy end points compared with placebo (39.3% vs 22.1%, P = .001 for CSBM1; 22.7% vs 11.4% P = .008 for CSBM2). Significantly greater improvements were seen with the vibrating capsule for the secondary end points of straining, stool consistency, and quality-of-life measures compared with placebo. Adverse events were mild, gastrointestinal in nature, and similar between groups, except that a mild vibrating sensation was reported by 11% of patients in the vibrating capsule group, but none withdrew from the trial. CONCLUSIONS: In patients with chronic constipation, the vibrating capsule was superior to placebo in improving bowel symptoms and quality of life. The vibrating capsule was safe and well tolerated. (Clinical trials.gov, Number: NCT03879239).

Novel Symptom Subgroups in Individuals With Irritable Bowel Syndrome Predict Disease Impact and Burden.

BACKGROUND & AIMS: Current classification systems based on bowel habit fail to capture the multidimensional nature of irritable bowel syndrome (IBS). We previously derived and validated a classification system, using latent class analysis, incorporating factors beyond bowel habit. We applied this in another cohort of people with IBS to assess its ability to capture the impact of IBS on the individual, the health care system, and society. METHODS: We collected demographic, symptom, and psychological health data from adults in the community self-identifying as having IBS, and meeting Rome IV criteria. We applied our latent class analysis model to identify the 7 subgroups (clusters) described previously, based on overall gastrointestinal symptom severity and psychological burden. We assessed quality of life, health care costs (£1 = $1.20), employment status, annual income, work productivity, and ability to perform work duties in each cluster. RESULTS: Of 1278 responders, 752 (58.8%) met Rome IV criteria. The 7-cluster model fit the data well. The patients in the 4 clusters with the highest psychological burden, and particularly those in cluster 6 with high overall gastrointestinal symptom severity and high psychological burden, showed lower educational levels, higher gastrointestinal symptom-specific anxiety, were more likely to have consulted a gastroenterologist, and used more drugs for IBS. IBS-related and generic quality of life were impaired significantly in these 4 clusters and significantly fewer individuals reported earning ≥£30,000 per year. Productivity and the ability to work, manage at home, engage in social and private leisure activities, and maintain close relationships all were impacted significantly, and IBS-related health care costs over the previous 12 months were highest in these 4 clusters. In those in cluster 6, costs were more than £1000 per person per year. CONCLUSIONS: Our clusters identify groups of individuals with significant impairments in quality of life, earning potential, and ability to work and function socially, who are high utilizers of health care.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

INTRODUCTION: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. METHODS: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. RESULTS: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was -2.66 for tenapanor vs -2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. DISCUSSION: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

Recent Developments in On-Demand Voiding Therapies.

One cannot survive without regularly urinating and defecating. People with neurologic injury (spinal cord injury, traumatic brain injury, stroke) or disease (multiple sclerosis, Parkinson's disease, spina bifida) and many elderly are unable to voluntarily initiate voiding. The great majority of them require bladder catheters to void urine and "manual bowel programs" with digital rectal stimulation and manual extraction to void stool. Catheter-associated urinary tract infections frequently require hospitalization, whereas manual bowel programs are time consuming (1 to 2 hours) and stigmatizing and cause rectal pain and discomfort. Laxatives and enemas produce defecation, but onset and duration are unpredictable, prolonged, and difficult to control, which can produce involuntary defecation and fecal incontinence. Patients with spinal cord injury (SCI) consider recovery of bladder and bowel function a higher priority than recovery of walking. Bladder and bowel dysfunction are a top reason for institutionalization of elderly. Surveys indicate that convenience, rapid onset and short duration, reliability and predictability, and efficient voiding are priorities of SCI individuals. Despite the severe, unmet medical need, there is no literature regarding on-demand, rapid-onset, short-duration, drug-induced voiding therapies. This article provides in-depth discussion of recent discovery and development of two candidates for on-demand voiding therapies. The first, [Lys3,Gly8,-R-γ-lactam-Leu9]-NKA(3-10) (DTI-117), a neurokinin2 receptor agonist, induces both urination and defecation after systemic administration. The second, capsaicin (DTI-301), is a transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor agonist that induces defecation after intrarectal administration. The review also presents clinical studies of a combination drug therapy administered via iontophoresis and preclinical studies of neuromodulation devices that induce urination and defecation. SIGNIFICANCE STATEMENT: A safe and effective, on-demand, rapid-onset, short-duration, drug-induced, voiding therapy could eliminate or reduce need for bladder catheters, manual bowel programs, and colostomies in patient populations that are unable to voluntarily initiate voiding. People with spinal injury place more importance on restoring bladder and bowel control than restoring their ability to walk. This paradigm-changing therapy would reduce stigmatism and healthcare costs while increasing convenience and quality of life.

Malnourished Microbes: Host-Microbiome Interactions in Child Undernutrition.

Childhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child undernutrition are characterized by derangements in multiple biological systems including metabolism, immunity, and endocrine systems. A growing body of evidence supports a role of the gut microbiome in mediating these pathways influencing early life growth. Observational studies report alterations in the gut microbiome of undernourished children, while preclinical studies suggest that this can trigger intestinal enteropathy, alter host metabolism, and disrupt immune-mediated resistance against enteropathogens, each of which contribute to poor early life growth. Here, we compile evidence from preclinical and clinical studies and describe the emerging pathophysiological pathways by which the early life gut microbiome influences host metabolism, immunity, intestinal function, endocrine regulation, and other pathways contributing to child undernutrition. We discuss emerging microbiome-directed therapies and consider future research directions to identify and target microbiome-sensitive pathways in child undernutrition.

Study on Intestinal Pressure after Implantation of Biaxial Actuated Artificial Anal Sphincter in Animal.

Fecal incontinence (FI) referred to the inability to control the leakage of solid, liquid, or gaseous feces, the artificial anal sphincter (AAS) was the last resort for patients with FI except enterostomy. In order to the clinical application value of AAS was improved, the detection and analysis of intestinal pressure information was very necessary. Biaxial actuated artificial anal sphincter (BAAS) was a new type of AAS, which not only had a stable, long-term and safe energy supply, but also could provide real-time feedback of intestinal pressure information. In this paper, the BAAS was implanted into piglets for a long-term animal experiment. Piglets' life habits, defecation habits and intestinal pressure were analyzed. The analysis results showed that the BAAS system had good feces control effect, when the actuator of the BAAS system was closed, there was basically no fecal leakage of piglets, and when the actuator of the BAAS system was opened, the piglets could defecate normally. Under the normal condition of the piglets' health state and the BAAS's operating state, the accuracy of the defecation perception reached to 65.79%. This study realized the in-depth study of the mechanism of piglets' defecation, and provided guidance for the development of a new generation of AAS.

Effects of chronic unpredictable mild stress on gut sensation and function in male mice.

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice's behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

The Severity of Fecal Problems Is Negatively Associated With Quality of Life in a Dutch Population Without Bowel Function Comorbidities.

BACKGROUND: Constipation and fecal incontinence negatively influence quality of life. The association between the severity of fecal problems and quality of life has not been investigated in the general population without bowel function comorbidities. OBJECTIVE: To investigate the association between the severity of constipation and fecal incontinence and quality of life in patients without comorbidities influencing bowel function. DESIGN: A population-based, cross-sectional study. SETTINGS: The study involved 3668 Dutch study participants. PATIENTS: A survey company conducted a population-wide study of the general Dutch population. Altogether, 5000 Dutch citizens completed the Groningen Defecation and Fecal Continence and Short Form-36 questionnaires. The data on 3668 respondents without comorbidities that could influence bowel function were included for analysis (study group). MAIN OUTCOME MEASURES: The severity of constipation (Agachan score) and fecal incontinence (Wexner score) in relation to the quality-of-life scores. RESULTS: In the study group (n = 3668), 487 had constipation (13.3%), 116 had fecal incontinence (3.2%), and 64 had 2 coexisting fecal problems (1.7%). In the multivariable analysis, all quality-of-life domains were negatively associated with the severity of constipation and fecal incontinence. The associations between the severity of constipation and quality of life were stronger (highest: ß = -2.413; 95% CI, -2.681 to -2.145; p < 0.001) than those of fecal incontinence (highest: ß = -1.280; 95% CI, -1.681 to -.880; p < 0.001). We also found that a longer duration of bowel complaints coincided with higher severity scores, especially for constipation. Respondents mostly rated their defecation health as positive, regardless of the severity of their fecal problems. LIMITATIONS: Cross-sectional design. CONCLUSIONS: The severity of constipation and fecal incontinence is significantly associated with reduced quality of life, with the severity of constipation having stronger associations than fecal incontinence. Given respondents' unawareness of their fecal problems and the progressive character, timely intervention is advocated. See Video Abstract . LA GRAVEDAD DE LOS PROBLEMAS FECALES SE ASOCIA NEGATIVAMENTE CON LA CALIDAD DE VIDA EN UNA POBLACIN HOLANDESA SIN COMORBILIDADES DE LA FUNCIN INTESTINAL: ANTECEDENTES:El estreñimiento y la incontinencia fecal influyen negativamente en la calidad de vida. La asociación entre la gravedad de los problemas fecales y la calidad de vida no se ha investigado en la población general sin comorbilidades de la función intestinal.OBJETIVO:Investigar la asociación entre la gravedad del estreñimiento y la incontinencia fecal y la calidad de vida en la población holandesa general sin comorbilidades que influyan en la función intestinal.DISEÑO:Estudio transversal de base poblacional.ENTORNO CLINICO:El estudio involucró a 3668 participantes holandeses.PACIENTES:Una empresa de encuestas realizó un estudio poblacional de la población holandesa en general. En total, 5.000 ciudadanos holandeses completaron los cuestionarios Groningen Defecation and Fecal Continence y Short-Form 36. Se incluyeron para el análisis los datos de 3668 encuestados sin comorbilidades que pudieran influir en la función intestinal (grupo de estudio).PRINCIPALES MEDIDAS DE RESULTADO:La gravedad del estreñimiento (puntuación de Agachan) y la incontinencia fecal (puntuación de Wexner) en relación con las puntuaciones de calidad de vida.RESULTADOS:En el grupo de estudio (n = 3668), 487 tenían estreñimiento (13,3%), 116 tenían incontinencia fecal (3,2%) y 64 tenían 2 problemas fecales coexistentes (1,7%). En el análisis multivariable, todos los dominios de calidad de vida se asociaron negativamente con la gravedad del estreñimiento y la incontinencia fecal. Las asociaciones entre la gravedad del estreñimiento y la calidad de vida fueron más fuertes (más alta: ß = -2,413; IC del 95 %, -2,681 a -2,145; p < 0,001) que las de la incontinencia fecal (más alta: ß = -1,280; 95 IC %: -1,681 a -0,880; p < 0,001). También encontramos que una mayor duración de las molestias intestinales coincidió con puntuaciones de gravedad más altas, especialmente para el estreñimiento. La mayoría de los encuestados calificaron su salud en la defecación como positiva, independientemente de la gravedad de sus problemas fecales.LIMITACIONES:Diseño transversal.CONCLUSIONES:La gravedad del estreñimiento y la incontinencia fecal se asocia significativamente con una calidad de vida reducida; la gravedad del estreñimiento tiene asociaciones más fuertes que la incontinencia fecal. Dado el desconocimiento de los encuestados sobre sus problemas fecales y el carácter progresivo, se recomienda una intervención oportuna. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Functional Disorders of the Ileal-Anal Pouch: A Systematic Review.

BACKGROUND: The IPAA is a boon to patients needing proctocolectomy but maintains per anal function through anatomic and physiologic compromises. The state of pouch function is hard to define because pouch anatomy is not normal and pouch physiology is a distortion of normal defecation. Patients with pouches develop multiple symptoms: some are expected, some are disease related, and some are the result of surgical complications. It is important to understand the cause of pouch-related symptoms so that appropriate management is offered. OBJECTIVES: The study aimed to review pouch symptoms and discuss their likely cause, review the literature on pouch function and dysfunction, and provide clarity to clear the confusion. DATA SOURCES: PubMed and Cochrane databases were searched using the terms "ileoanal pouch function" and "ileoanal pouch dysfunction." STUDY SELECTION: From 1983 to 2023, 553 articles related to "ileoanal pouch function" and 178 related to "ileoanal pouch dysfunction" were reviewed. Nine studies appeared under both headings. Case studies, duplicate publications, and articles concerning pouch diseases were excluded. MAIN OUTCOME MEASURES: Definitions of pouch function and dysfunction, methods of describing and scoring symptoms, and understanding of expected changes in pouch function given the nature of the surgery. RESULTS: Twenty-seven studies were reviewed from the ileoanal pouch dysfunction search and 38 from ileoanal pouch function. Three studies tried to define normal pouch function, 10 attempted to measure pouch function, and 4 aimed to score pouch function. Only 3 studies addressed pouch physiology. LIMITATIONS: A full discussion of pouch dysfunction is limited by the lack of studies focussing on the anatomic and physiologic consequences of turning the terminal ileum into an organ of storage. CONCLUSIONS: Most studies of pouch function and dysfunction do not consider expected changes in the physiology of defecation that follow restorative proctocolectomy. Thus, most studies of pouch function produce conclusions that lack an important dimension. See video from symposium.

Defecation Symptoms in Relation to Stool Consistency Significantly Reflect the Dyssynergic Pattern in High-resolution Anorectal Manometry in Constipated Patients.

GOALS: To evaluate the usefulness of a 2-week patient-completed bowel habit and symptom diary as a screening tool for disordered rectoanal coordination (DRC). BACKGROUND: DRC is an important subgroup of chronic constipation that benefits from biofeedback treatment. Diagnosis of DRC requires a dyssynergic pattern (DP) of attempted defecation in high-resolution anorectal manometry (HRAM) and at least 1 other positive standardized examination, such as the balloon expulsion test or defecography. However, HRAM is generally limited to tertiary gastroenterology centres and finding tools for selecting patients for referral for further investigations would be of clinical value. STUDY: Retrospective data from HRAM and a 2-week patient-completed bowel habit and symptom diary from 99 chronically constipated patients were analyzed. RESULTS: Fifty-seven percent of the patients had a DP pattern during HRAM. In the DP group, 76% of bowel movements with loose or normal stool resulted in a sense of incomplete evacuation compared with 55% of the non-DP group ( P =0.004). Straining and sensation of incomplete evacuation with the loose stool were significantly more common in the DP group ( P =0.032). Hard stool was a discriminator for non-DP ( P =0.044). Multiple logistic regression including incomplete evacuation and normal stool predicted DP with a sensitivity of 82% and a specificity of 50%. CONCLUSIONS: The sensation of incomplete evacuation with loose or normal stool could be a potential discriminator in favor of DP in chronically constipated patients. The bowel habit and symptom diary may be a useful tool for stratifying constipated patients for further investigation of suspected DRC.

Defecation symptoms in primary health care patients with irritable bowel syndrome.

BACKGROUND: The objectives of the present study were to (a) measure the prevalence of defecation symptoms in IBS, (b) investigate the relationship between stool consistency and defecation symptoms in IBS, and (c) investigate the association of defecation symptoms with health-related quality of life (HRQL) and self-reported stress in patients with IBS cared for in a primary health care setting. METHODS: Ten primary health care centres joined the study. 282 patients with IBS as well as 372 non-IBS controls filled in gastrointestinal symptom diaries prospectively for two weeks as well as the Perceived Stress Scale-14 (PSS14) and the EuroQol barometer to measure perceived stress and HRQL, respectively. RESULTS: Incomplete evacuation was present in 51% vs. 21% of the stools among the IBS patients and the non-IBS controls, respectively. The need to strain during defecation was existing in 41% vs. 33% of the stools for the IBS patients and the non-IBS controls, respectively. Urgency was experienced in 37% of the stools in the IBS patients compared with 18% of the stools in the non-IBS controls. Patients with IBS experienced in a significant higher degree of overlapping symptoms per stool (p < 0.001 to p = 0.007). The occurrence of all defecation symptoms in the same patient was related to decreased HRQL, and increased stress (p = 0.001 to p < 0.001). CONCLUSIONS: An overlap between IBS and symptoms from the anorectal region related to defecation was found in a primary health care population. Defecation symptoms are very common in primary care IBS-patients, it co-occurs with increased self-perceived stress, and decreased HRQL.

Effects on anorectal function of endoscopic submucosal dissection for rectal tumors involving the dentate line.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is a specific procedure that uses an electrosurgical knife for en-bloc resectioning large tumors. However, no study has examined the effect of ESD on the defecation function of patients with rectal tumors. We aimed to investigate the potential effects caused by ESD by analyzing changes in the morphology and movement of the anorectum pre- and post-ESD. METHODS: This prospective observational study included 11 patients with anorectal tumors who underwent ESD between April 2020 and February 2022. Pre-ESD assessments included anorectal manometry and defecography. Post-ESD assessments were conducted 2 months later, including anorectal manometry, defecography, and proctoscopy for ulcer and stenosis evaluation. RESULTS: The median patient age was 73 years, including seven males and four females. Eight patients (73%) had a tumor in the lower rectum, and the extent of resection was less than 50% of the rectal lumen. Resection reached the dentate line in six cases (55%). In the patients with post-ESD mucosal defects involving the dentate line, the median of functional anal canal length significantly decreased from (3.4 cm pre-ESD to 2.8 cm post-ESD, p = 0.04). Defecography revealed one case with incomplete evacuation (<50%) and incontinence post-ESD. Interestingly, patients with pre-existing rectoceles noted resolution of lesions post-ESD. None of the patients reported daily constipation or fecal incontinence. CONCLUSIONS: While rectal ESD is unlikely to cause significant real-world defecation difficulties, alterations in rectal and anal canal morphology and function may occur if the dentate line is involved in the resection range.

Opium tincture has anti-propulsive effects in patients with chronic diarrhea: a randomized, placebo-controlled, and cross-over trial.

OBJECTIVE: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. MATERIALS AND METHODS: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. RESULTS: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. CONCLUSION: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found.Trial Registration Number: NCT05690321 (registered 2023-01-10).

Influence of the examination position and distension medium on the rectal sensory test in patients with functional constipation.

PURPOSE: To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice. METHODS: Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums. RESULTS: Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P < 0.05). In terms of research on distension medium, it was found that the first constant sensation volume measured in the squatting position (when the distension medium was water) was significantly lower than that of gas (P < 0.05). CONCLUSION: For patients with functional constipation, there are differences in the results of rectal sensory tests between body positions and distension mediums. When conducting multicenter studies, it is necessary to unify the standard operating procedure (SOP) for operational details to ensure consistency and reliability of the test results.

High-resolution anorectal manometry for diagnosing obstructed defecation syndrome associated with moderate rectocele compared to healthy individuals.

BACKGROUND: Few studies have investigated healthy female individuals (HFI) and those with obstructed defecation syndrome associated with moderate rectocele in women (MRW), identified using three-dimensional high-resolution anorectal manometry (3D HRAM) parameters that correlate with age stratification. OBJECTIVE: We aimed to explore the clinical diagnostic values of the MRW and HFI groups using 3D HRAM parameters related to age stratification. METHODS: A prospective non-randomized controlled trial involving 128 cases from the MRW (treatment group, 68 cases) and HFI (control group, 60 cases) groups was conducted using 3D HRAM parameters at Tianjin Union Medical Center between January 2017 and June 2022, and patients were divided into two subgroups based on their ages: the ≥50 and < 50 years subgroups. RESULTS: Multivariate binary logistic regression analysis showed that age (P = 0.024) and rectoanal inhibitory reflex (P = 0.001) were independent factors affecting the disease in the MRW group. Compared to the HFI group, the receiver operating characteristic (ROC) curve demonstrated that the 3D HRAM parameters exhibited a higher diagnostic value for age (Youden index = 0.31), urge to defecate (Youden index = 0.24), and rectoanal pressure differential (Youden index = 0.21) in the MRW group. CONCLUSIONS: Compared to the HFI group, the ROC curve of the 3D HRAM parameters suggests that age, urge to defecate, and rectoanal pressure differential in the MRW group have a significant diagnostic value. Because the Youden index is lower, 3D HRAM cannot be considered the gold standard method for diagnosing MRW.

Assessing anorectal function in patients with recurrent ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is an inflammatory bowel disease with an unclear etiology that can lead to irreversible changes in distal colonic function in chronic patients. This study investigated anorectal function in recurrent UC patients and identified influencing factors. METHODS: This prospective study enrolled 33 recurrent UC patients and 40 newly diagnosed patients from January 2019 to December 2022. Data collection included clinical records, scores, and anorectal function assessments. Regression analyses were used to identify factors impacting anorectal function. RESULTS: Recurrent UC patients had higher baseline CRP and fecal calprotectin levels, increased anxiety and depression, and more severe fecal incontinence. They also had lower BMIs, serum Hb and albumin (ALB) levels, and Inflammatory Bowel Disease Questionnaire scores than did initial-onset UC patients. Multivariate linear regression analysis revealed that long disease duration (coef. - 0.376, P < 0.001) and high fecal calprotectin level (coef. - 0.656, P < 0.001) independently influenced the initial sensation threshold in recurrent UC patients. Additionally, high fecal calprotectin (coef. - 0.073, P = 0.013) and high Zung Self-Rating Anxiety Scale score (coef. - 0.489, P = 0.001) were identified as two independent determinants of the defecation volume threshold. For the defecation urgency threshold, the independent factors included high disease duration (coef. - 0.358, P = 0.017) and high fecal calprotectin level (coef. - 0.499, P = 0.001). Similarly, the sole independent factor identified for the maximum capacity threshold was high fecal calprotectin (coef. - 0.691, P = 0.001). CONCLUSION: Recurrent UC patients had increased rectal sensitivity and compromised anorectal function, which significantly impacted quality of life. Proactively managing the disease, reducing UC relapses, and addressing anxiety are effective measures for improving anorectal function in these patients.

Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.

Constipated patients with functional defecatory disorder have secondary rectal hyposensitivity due to altered rectal biomechanics.

BACKGROUND AND AIM: Rectal hyposensitivity (RH) is common in constipation and often coexists with functional defecatory disorder (FDD). Rectal sensory thresholds are routinely evaluated with the anorectal manometry probe; however, the gold standard for the assessment of rectal sensitivity is with a barostat, use of which is limited by time constraints and availability. A novel rapid barostat bag (RBB) may facilitate measurements of rectal sensitivity. The aim is to evaluate the relationship between RH (measured by the RBB) and FDD (defined as any minor disorder of rectoanal coordination by the London classification) in constipated patients. METHODS: Consecutive constipated patients referred for anorectal function testing underwent anorectal manometry with the 3D-HDAM probe as well as rectal sensation testing with the RBB pump. RH was defined by volume to first sensation >30%, urge to defecate >80%, or discomfort >100% (normalized to rectal capacity). RESULTS: Fifty-three percent of constipated patients had RH. Patients with FDD had a significantly increased volume to first sensation (134.5 mL vs 102.0, P = 0.02), urge to defecate (187.0 mL vs 149.0, P = 0.04), and rectal capacity (253.5 mL vs 209.0, P = 0.04) compared to constipated patients without FDD. There was no difference in normalized sensory thresholds (percent of rectal capacity) nor the prevalence of hyposensitivity to each sensory threshold nor overall hyposensitivity. CONCLUSION: Patients with FDD, when measured with the RBB, have increased sensory thresholds on volumetric distension, but RH was not observed when sensory threshold volume were normalized to rectal capacity. This may reflect "secondary" RH due to altered rectal biomechanics.