Targeting the pylorus in gastroparesis: From physiology to endoscopic pyloromyotomy.

BACKGROUND: The pylorus plays a key role in the control of gastric content outflow. Impairment of pyloric physiology has been observed in gastroparesis, particularly when associated with diabetes mellitus or opioid intake or after antireflux surgery. New tools have been developed to identify pyloric dysfunction in routine care, including functional luminal impedance planimetry (FLIP). As such, a new therapeutic strategy targeting the pylorus, namely endoscopic pyloromyotomy (G-POEM), has received increasing attention and emerged as a promising treatment for gastroparesis. PURPOSE: The present review details the involvement of the pyloric pathophysiology in gastroparesis, as well as clinical results of G-POEM according to the current literature.

Relationship between anal functional lumen imaging probe (EndoFLIP®) results and the clinical presentation of faecal incontinence.

AIM: Faecal incontinence (FI) subtypes (urge, passive, mixed) are linked to the physiopathological mechanism of FI. Previous studies have failed to demonstrate a consistent relationship between FI subtype and anal sphincter dysfunction. Our aim was to evaluate the relationship between anal sphincter function, assessed using the new EndoFLIP® technology, and FI subtype. METHOD: Patients referred for FI were prospectively enrolled between October 2015 and May 2021 in a registry, and data were retrospectively examined. Each patient underwent a clinical assessment as well as three-dimensional high-resolution or water-perfused anorectal manometry, anal EndoFLIP®, and anorectal electrophysiological and endoanal ultrasound tests. The results of the investigations were compared across FI subtypes. RESULTS: The cohort included 133 patients, 54 (41%) of whom met the criteria for urge FI, 40 (30%) for passive FI and 39 (29%) for mixed FI. The resting anal distensibility index (DI) at 50 ml of distension was significantly lower in patients with urge FI than in patients with passive FI (p = 0.04). At rest, a DI at 50 ml of distension ≥7.3 mm2  mmHg-1 and a DI at 40 ml of distension <1.3 mm2  mmHg-1 were associated with the passive and urge FI subtypes, respectively, with poor discriminatory power (an accuracy of 0.49 compared with 0.33 for random assignment). There were no differences in anorectal manometry, endoanal ultrasound or electrophysiological test results among the urge, passive and mixed FI subgroups (all p > 0.05). CONCLUSION: The anal sphincter DI using the EndoFLIP® system displayed poor predictive performance in distinguishing among FI subtypes.

Overlaps with bladder pain syndrome and irritable bowel syndrome are associated with higher symptom burden and reduced quality of life in functional dyspepsia.

BACKGROUND: Functional dyspepsia and bladder pain syndrome are well-known to overlap with irritable bowel syndrome. Whether functional dyspepsia overlaps with bladder pain syndrome remains unknown. Our aim was to evaluate the presence of bladder pain syndrome in functional dyspepsia patients and its impact. METHODS: All consecutive patients with investigated dyspeptic symptoms in our tertiary care center between March 2015 and November 2018 were studied. Functional dyspepsia and irritable bowel syndrome were diagnosed according to Rome III and IV criteria while bladder pain syndrome was diagnosed using ESSIC criteria. Validated questionnaires were filled to assess quality of life (GIQLI), anxiety and depression (HADS), sleep (PSQI), and insomnia (ISI). Dyspeptic symptoms severity was assessed individually for eight dyspeptic complaints. KEY RESULTS: Among 1453 patients with dyspeptic symptoms, 61.4% fulfilled Rome criteria for functional dyspepsia. Bladder pain syndrome was present in 16.0% of the patients not fulfilling diagnostic criteria for functional dyspepsia, 22.2% of patients with functional dyspepsia alone, and 36.4% of patients with overlapping functional dyspepsia and irritable bowel syndrome (p-values <0.0001). In patients with bladder pain syndrome overlapping with functional dyspepsia, dyspeptic symptoms severity, anxiety, depression, and insomnia levels were higher while quality of life and sleep quality were reduced (p-values <0.0001). These results were even more pronounced in case of overlap with irritable bowel syndrome (p-values <0.0001). CONCLUSIONS AND INFERENCES: Bladder pain syndrome is present in 26.9% of functional dyspepsia patients and is associated with higher gastrointestinal, psychological distresses, and sleep symptom burdens, and with reduced quality of life.

Delayed gastric emptying as an independent predictor of mortality in gastroparesis.

BACKGROUND: Whether gastroparesis is associated with a shortened life expectancy remains uncertain as no systematic study has evaluated the impact of gastroparesis on mortality, based on gastric emptying (GE) tests. AIM: This study aimed to assess whether delayed GE was predictive of mortality. METHODS: GE was measured using a 13C-octanoic acid breath test in 1563 consecutive patients. Delayed GE at baseline defined the gastroparesis group. Patients were followed up for a mean of 8.9 years, yielding 13 466 patients per year. Mortality was assessed using the French CepiDc database with data from local civil registries. The cause of death was determined from medical records. Mortality rates were assessed using the Kaplan-Meier method and hazard ratio (HR) was calculated using the Cox regression model. RESULTS: Age and symptoms severity were not different among patients with normal GE (n = 1179) and with delayed GE (n = 384) while diabetes mellitus was more frequent in the gastroparesis group. Kaplan-Meier analysis showed increased mortality in the gastroparesis group compared to patients with normal GE. Cox regression model identified delayed GE as independently associated with increased mortality (HR = 1.63[1.09-2.42]; P = 0.02). Other independent factors associated with increased mortality included age, male sex, and diabetes. No difference was observed between groups for the cause of death, with cancer and cardiovascular disease being the leading causes. CONCLUSION: This study has shown that gastroparesis, diagnosed on GE tests, was associated with increased mortality, independently of age, sex, BMI or diabetes status (NCT04918329).

Ten-year Evaluation of a Large Retrospective Cohort Treated by Sacral Nerve Modulation for Fecal Incontinence: Results of a French Multicenter Study.

OBJECTIVE: The aim of this study was to assess the effectiveness of sacral nerve modulation (SNM) in a large cohort of patients implanted for at least 10 years, quantify adverse event rates, and identify predictive factors of long-term success. SUMMARY BACKGROUND DATA: Few studies have evaluated the long-term success of SNM. METHODS: Data collected prospectively from patients implanted for fecal incontinence (FI) in 7 French centers between January 1998 and December 2008 were retrospectively analyzed. Patient FI severity scores were assessed before and 10 years after implantation. The main evaluation criterion was the success of SNM defined by the continuation of the treatment without additional therapies. The secondary evaluation criteria were the rate of device revisions and explantations. Preoperative predictors of success at 10 years were sought. RESULTS: Of the 360 patients (27 males, mean age: 59 ± 12 years) implanted for FI, 162 (45%) had a favorable outcome 10 years post-implantation, 115 (31.9%) failed, and 83 (23.1%) were lost to follow-up. The favorable outcome derived from the time-to-event Kaplan-Meier curve at 10 years was 0.64 (95% CI 0.58-0.69). FI severity scores were significantly better 10 years post-implantation compared to preimplantation (7.4 ± 4.3 vs 14.0 ± 3.2; P < 0.0001). During the 10-year follow-up, 233 patients (64.7%) had a surgical revision and 94 (26.1%) were explanted. A history of surgery for FI and sex (male) were associated with an increased risk of an unfavorable outcome. CONCLUSIONS: Long-term efficacy was maintained in approximately half of the FI patients treated by SNM at least 10 years post-implantation.

Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice.

BACKGROUND: Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory pathways, it is likely that those syndromes involve a cross-sensitization of the bladder and the colon. The precise pathophysiology remains poorly understood. AIM: To develop a model of chronic bladder-colon cross-sensitization and to investigate the mech-anisms involved. METHODS: Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane anesthesia. Colorectal sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal distensions. Myeloperoxidase, used as a marker of colorectal inflammation, was measured in the colon, and colorectal permeability was measured using chambers. c-Fos protein expression, used as a marker of neuronal activation, was assessed in the spinal cord (L6-S1 level) using immunohistochemistry. Green fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal cord. The expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western blot. RESULTS: Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid vs saline (P < 0.0001). This effect started 1 h post-injection and lasted up to 7 d post-injection. No increased permeability or inflammation was shown in the bladder or colon 7 d post-injection. Visceral hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord (P < 0.0001). In green fluorescent protein on the fractalkine receptor-positive mice, intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord (P < 0.0001). NK1 receptor and MAPK-p38 levels were increased in the spinal cord up to 7 d after injection (P = 0.007 and 0.023 respectively). Colorectal sensitization was prevented by intrathecal or intracerebroventricular injections of minocycline, a microglia inhibitor, by intracerebroventricular injection of CP-99994 dihydrochloride, a NK1 antagonist, and by intracerebroventricular injection of SB203580, a MAPK-p38 inhibitor. CONCLUSION: We describe a new model of cross-organ visceral sensitization between the bladder and the colon in mice. Intravesical injections of acetic acid induced a long-lasting colorectal hypersensitivity to distension, mediated by neuroglial interactions, MAPK-p38 phosphorylation and the NK1 receptor.

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

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

Is it necessary to perform a morphological assessment for an esophageal motility disorder? A retrospective descriptive study.

BACKGROUND: Esophageal motility disorders are most often of primary origin but may be secondary to an occult malignancy or another etiology. High-resolution esophageal manometry cannot differentiate between secondary or primary origin. This study aimed at discussing the usefulness of a morphological assessment in the diagnosis of specific esophageal motility disorders, and to establish the predictive factors of a potential secondary origin. METHODS: In this retrospective study, patients with suspected esophageal motility disorders who underwent an esophageal manometry were included. High-resolution manometry results were interpreted according to the Chicago Classification, 3rd version. The results of endoscopic ultrasound and computed tomography, assessed by a panel of experts, allowed to diagnose a secondary origin. KEY RESULTS: Out of 2138 patients undergoing manometry, 502 patients had a esophageal motility disorder suspect to be from secondary origin; among them 182 patients underwent tomography or endoscopic ultrasound. According to experts, 16 patients (8.8%) had a secondary esophageal motility disorder: esophagogastric junction outflow obstruction (n = 7), jackhammer disorder (n = 4), achalasia (n = 3) and localized pressurization (n = 2). The etiology was malignant in 8 patients. Predictive factors suggesting potential secondary esophageal motility disorders were smoking, age ≥ 58 years and an Integrated Relaxation Pressure higher than 10 mmHg for water swallows. CONCLUSION AND INFERENCES: Esophageal motility disorders with organic origin are not uncommon. A morphological assessment using endoscopic ultrasonography and/or computed tomography may be of use to diagnose a secondary origin, especially in the elderly and smokers.

Assessment of pyloric sphincter distensibility and pressure in patients with diabetic gastroparesis.

BACKGROUND: Recent studies have shown that pyloric distensibility is altered in 30-50% of gastroparetic patients but the number of diabetic patients included in prior reports has been small. The aim of the present study was to assess pyloric sphincter measurements in diabetic patients with gastroparesis and to determine whether diabetes characteristics were correlated to pyloric disfunction. METHODS: Pyloric distensibility and pressure were measured using EndoFLIP® system in 46 patients with diabetic gastroparesis (DGP) and compared with 21 healthy volunteers (HV), and 33 patients with idiopathic gastroparesis (IGP). Altered pyloric distensibility was defined as the measurement below 10 mm2 /mmHg at 40 ml of inflation. In diabetic patients, blood glucose, glycated hemoglobin, duration, complications, and treatments were collected. KEY RESULTS: Mean pyloric distensibility at 40 ml of inflation was lower in DGP and IGP groups with, respectively, 10.8 ± 0.9 mm2 /mmHg and 14.8 ± 2.2 mm2 /mmHg in comparison with the HV group (25.2 ± 2.3 mm2 /mmHg; p < 0.005). 56.5% of patients had a decreased pyloric distensibility in the DGP group, 51.5% of patients in the IGP group, and 10% of patients in the HV group. No correlation was found between pyloric sphincter measurements and diabetes characteristics, including blood glucose, glycated hemoglobin, diabetes mellitus type, neuropathy, or GLP1 agonists intake. CONCLUSION AND INTERFERENCES: Pyloric sphincter distensibility and pressure were altered both in diabetic and idiopathic gastroparesis. Pyloric sphincter distensibility was not correlated to diabetes parameters.

Jackhammer esophagus: Clinical presentation, manometric diagnosis, and therapeutic results-Results from a multicenter French cohort.

BACKGROUND/AIMS: Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000 mm Hg.s.cm during high-resolution manometry (HRM). The relationship between symptoms and hypercontractility and the response to therapies have been poorly evaluated. The aim of this study was to determine the clinical presentation, manometric diagnosis, and therapeutic results in a large cohort of JE patients. METHODS: Patients with JE diagnosed among the HRM tests performed in nine academic French centers from 01/01/2010 to 08/31/2016 were included. Patient charts were reviewed to collect clinical and therapeutic data. RESULTS: Among the 16 264 HRM tests performed during this period, 227 patients (60.8 ± 13.8 years, 151 male) had JE (1.7%). Dysphagia was the most frequent symptom (74.6%), followed by regurgitation (37.1%) and chest pain (36.6%); 4.7% of the patients were asymptomatic. The diagnostic workup was heterogeneous, and only a minority of patients had esophageal biopsies. None of the individual symptoms were significantly associated with any of the manometric parameters defined, except for dysphagia, which was significantly associated with the mean of all DCIs >8000 mm Hg.s.cm (P = .04). Additionally, the number of symptoms was not associated with any manometric parameter. Medical treatment and endoscopic treatments had poor efficacy and a high relapse rate. CONCLUSION: Jackhammer esophagus is a rare motility disorder. Diagnostic workup is heterogeneous and should be standardized. Symptoms are poorly associated with manometric parameters. The medical treatments and endoscopic therapies currently used are inefficient.

Pyloric distensibility measurement after gastric surgery: Which surgeries are associated with pylorospasm?

BACKGROUND AND STUDY AIMS: History of gastric surgery is found in 10% of patients with gastroparesis, and vagal lesion is often suspected to be the cause of pylorospasm. Recently, pyloric distensibility measurement using the EndoFLIP® system showed that pylorospasm was present in 30%-50% of gastroparetic patients. Our objective was to assess whether pylorospasm, diagnosed using EndoFLIP® system was observed in three different types of gastric surgeries: antireflux surgery, sleeve gastrectomy, and esophagectomy. PATIENTS AND METHODS: Pyloric distensibility and pressure were measured using the EndoFLIP® system in 43 patients from two centers (18 antireflux surgery, 16 sleeve gastrectomy, and nine esophagectomy) with dyspeptic symptoms after gastric surgery, and in 21 healthy volunteers. Altered pyloric distensibility was defined as distensibility below 10 mm2 /mm Hg as previously reported. RESULTS: Compared to healthy volunteers (distensibility: 25.2 ± 2.4 mm2 /mm Hg; pressure: 9.7 ± 4.4 mm Hg), pyloric distensibility was decreased in 61.1% of patients in the antireflux surgery group (14.5 ± 3.4 mm2 /mm Hg; P < .01) and 75.0% of patients in the esophagectomy group (10.8 ± 2.1 mm2 /mm Hg; P < .05), while pyloric pressure was only increased in the antireflux surgery group (18.9 ± 2.2 mm Hg; P < .01). Pyloric distensibility and pressure were similar in healthy volunteers and in sleeve gastrectomy (distensibility: 20.3 ± 3.8 mm2 /mm Hg; pressure: 15.8 ± 1.6 mm Hg) groups, with decreased pyloric distensibility affecting 18.7% of sleeve gastrectomy patients. CONCLUSION: Antireflux surgery and esophagectomy were associated with pylorospasm although pylorospasm was not found in all patients. Sleeve gastrectomy was not associated with altered pyloric distensibility nor altered pyloric pressure.

Assessment of anal sphincter distensibility following the STARR procedure: a pilot study.

Aim: The STARR (Stapled Trans-Anal Rectal Resection) procedure consists of a surgical correction of symptomatic rectocele refractory to medical treatment, involving anal dilatation. The aim of the study was to determine the impact of the STARR procedure on anal distensibility using EndoFLIP® device.Methods: All female patients with a minimal rectocele of 3 cm and with symptoms of obstructed defecation syndrome (ODS) refractory to medical treatment were included prospectively. Patients with previous anal incontinence were not included. Wexner, ODS and Kess scores were recorded. Endoanal ultrasounds and EndoFLIP® measurements were performed pre-surgery and 3 months following the STARR procedure. The distensibility index (DI) at 40 mL of inflation at rest was the primary study endpoint.Results: Seven patients (median age: 52.5, range: 44-62) were included between 2014 and 2017. The DI after surgery was the same as the pre-surgery DI. No patient developed symptoms of faecal incontinence or urge to defecate in the three months following the STARR procedure. All patients reported an improvement in their ODS and Kess scores three months after the STARR procedure. No anal sphincter defects were detected by endoanal ultrasound.Conclusion: Anal dilatation did not appear to alter anal distensibility in patients with a normal anal function before the STARR procedure.

Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism.

Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK)-/-] and wild-type (WT) littermate mice were used and received a 20%-fructose (KHK-F and WT-F) or 20%-glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK-F mice. In KHK-F mice, triple-label immunohistochemistry showed major up-regulation of CCK in enteroendocrine cells (EECs) that were glucagon-like peptide-1 (GLP-1)+/Peptide YY (PYY-) in the ileum and colon and GLP-1-/PYY- in the cecum. The cecal microbiota composition was drastically modified in the KHK-F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption-dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI-H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota-dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.-Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero-Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism.

Outcomes and Future Directions of Per-Oral Endoscopic Pyloromyotomy: A View from France.

Gastroparesis is a challenging functional gastroenterological disorder, the complex pathophysiology of which hampers development of therapeutic modalities. Per-oral pyloromyotomy (POP) is a promising endoscopic therapy with a short-term clinical success rate of greater than 80%. Interest in POP is increasing, particularly in France, a country in which there is considerable expertise in submucosal endoscopy and functional disorders. Long-term follow-up and pyloric function evaluation are needed to assess the efficacy of POP in gastroparetic patients.

Endoflip vs high-definition manometry in the assessment of fecal incontinence: A data-driven unsupervised comparison.

BACKGROUND: How much anal sphincter dysfunction contributes to fecal incontinence (FI) is not clear. High-definition anorectal manometry (HDAM) and functional luminal imaging probe (Endoflip) are two new techniques to study anal sphincter function. AIMS: The goal was to compare the diagnostic utility of HDAM and Endoflip using optimal feature(s) in each modality for FI diagnosis. METHODS: Blinded classification was carried out on 70 female subjects (32 FI & 38 controls), using 3 prominent machine-learning clustering techniques, with 3 distance metrics. For HDAM, descriptive statistics, shape, and textural features characterizing the spatial relationship of pixels in the HDAM high-pressure zone, and for Endoflip, permutations of pressure and CSA combinations (ie, multiplication, division, or individually) at rest and squeeze were tested. RESULTS: Intramodality: (a) Endoflip: Best clustering was obtained using the combination of the ratio of CSA over pressure at 40 and 50 mL at rest, which had significantly better specificity (P < 0.001) than using only pressure at 50 mL, no difference in sensitivity (P = 0.68). (b) HDAM: clustering using textural information at rest had significantly higher specificity compared to using only the maximal pressure at rest (P < 0.001). Intermodality: Clustering results using optimal features were not significantly different with respect to sensitivity or specificity (P > 0.05). Optimal Endoflip feature set differed significantly in specificity compared to HDAM maximal pressure at both rest (P < 0.001) and squeeze (P < 0.001). CONCLUSION: Defective anal closure function is fairly sensitive and highly specific in diagnosing FI. Using optimal feature sets, HDAM and Endoflip perform in a similar fashion in diagnosing FI, but are not complementary.

Does calprotectin level identify a subgroup among patients suffering from irritable bowel syndrome? Results of a prospective study.

BACKGROUND: Irritable bowel syndrome is a multifactorial disease. Although faecal calprotectin has been shown to be a reliable marker of intestinal inflammation, its role in irritable bowel syndrome remains debated. OBJECTIVE: The aims of this prospective study were to select a subgroup of irritable bowel syndrome patients and to characterise those patients with high faecal calprotectin by systematic work-up. METHODS: Calprotectin levels were determined by enzyme-linked immunosorbent assay test in consecutive irritable bowel syndrome patients fulfilling Rome III criteria in whom normal colonoscopy and appropriate tests had excluded organic disease. Calprotectin levels were compared in irritable bowel syndrome patients, healthy controls and patients with active and quiescent Crohn's disease. When the calprotectin level was higher than 50 µg/g, the absence of ANCA/ASCA antibodies and a normal small bowel examination were required to confirm irritable bowel syndrome diagnosis. Additional explorations included assessment of irritable bowel syndrome severity, anxiety and depression, impact on quality of life, glucose and fructose breath tests, rectal distension test by barostat and quantitative and qualitative assessment of inflammation on colonic biopsies. RESULTS: Among the 93 irritable bowel syndrome patients (73% women; 66.7% with diarrhoea) recruited, 34 (36.6%) had reproducibly elevated calprotectin. Although they tended to be older than those with normal calprotectin (P = 0.06), there were no other differences between the two groups. When elevated, calprotectin was correlated with age (P = 0.03, r = 0.22). CONCLUSIONS: Elevated faecal calprotectin was observed in one third of patients in this series, without any significant association with a specific clinical phenotype (except age) or specific abnormalities.

Botulinum toxin: an endoscopic approach for treating fecal incontinence.

BACKGROUND AND STUDY AIMS: Fecal incontinence is a common, distressing condition with limited therapeutic options. Botulinum toxin A (BTX-A) injections have been proposed as a treatment for patients with fecal incontinence. This study aimed to determine the short-term clinical outcomes of BTX-A injections in patients with fecal incontinence of varying etiology. PATIENTS AND METHODS: Twenty-six patients with fecal incontinence were enrolled, 17 with their native rectum and 9 with a neo-reservoir following a proctectomy for rectal cancer. BTX-A was endoscopically injected into the rectum/reservoir. Scores for severity (CCS) and quality of life (FIQL) were recorded at baseline and at the 3-month follow-up visit. RESULTS: The CCS was significantly lower after 3 months (median 15, range 4 - 20 vs. 8, range 1 - 19; P = 0.001). The quality of life improved in three of the four FIQL domains. The improvement was maintained in 11 of 12 patients who received more than one injection because of recurrent symptoms. There was no significant predictive factor for the success of BTX-A injections. CONCLUSION: This preliminary study demonstrated that rectal/reservoir injections are an effective short-term treatment for fecal incontinence.

Are digestive symptoms in women presenting with pelvic endometriosis specific to lesion localizations? A preliminary prospective study.

STUDY QUESTION: What are the types and frequency of digestive symptoms in patients with different localizations of pelvic endometriosis and which specific symptoms are related to rectal stenosis? SUMMARY ANSWER: There is a high prevalence of digestive complaints in women presenting with superficial pelvic endometriosis and deep endometriosis sparing the rectum. WHAT IS KNOWN ALREADY: Women presenting with pelvic endometriosis frequently report gastrointestinal complaints of increased intensity during menstruation, which are not necessarily linked to the infiltration of the disease into the rectal wall. Even though intrarectal protrusion of the nodule can have an impact on bowel movement, only a minority of women with rectal nodules seemed to be concerned by significant narrowing of the rectum. STUDY DESIGN AND SIZE: This three-arm cohort prospective study included 116 women and was carried out over 22 consecutive months. PARTICIPANTS, SETTING AND METHODS: Prospective recording of data was performed for women treated for Stage 1 endometriosis involving the Douglas pouch (n = 21), deep endometriosis without digestive infiltration (n = 42) and deep endometriosis infiltrating the rectum (n = 53). Patient characteristics, pelvic pain and data from preoperative standardized questionnaires The Gastrointestinal Quality of Life Index (GIQLI), the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS) and the MOS 36-Item Short-Form Health Survey (SF-36) were compared according to endometriosis localization. MAIN RESULTS: The values of total KESS and total GIQLI score were comparable for the three groups, as were a majority of the digestive complaints. Women presenting with rectal endometriosis were more likely to report an increase in intensity and length of dysmenorrhoea, while deep dyspareunia appeared to be more severe in women with superficial endometriosis. Women presenting with rectal endometriosis were more likely to present cyclic defecation pain (67.9%), cyclic constipation (54.7%) and a significantly longer stool evacuation time, although these complaints were also frequent in the other two groups (38.1 and 33.3% in women with Stage 1 endometriosis and 42.9 and 26.2% in women with deep endometriosis without digestive involvement, respectively). No independent clinical factor was found to be related to infiltration of the rectum by deep endometriosis. Among women with rectal endometriosis, only 26.4% presented with rectal stenosis. These women were significantly more likely to report constipation, defecation pain, appetite disorders, longer evacuation time and increased stool consistency without laxatives. LIMITATIONS: Patients treated for pelvic endometriosis in a tertiary referral centre may not be representative of the general endometriosis population presenting with those lesions. Statistically significant differences were revealed between the three groups; however, the results were based on a small number of subjects, which carries an inherent risk of type II error particularly when comparing variables with closed values. WIDER IMPLICATIONS OF THE FINDINGS: In women presenting with pelvic endometriosis, it seems likely that various digestive symptoms are the consequence of cyclic inflammatory phenomena leading to irritation of the digestive tract, rather than to actual infiltration of the disease itself into the rectum, with the exception of a limited number of cases where the disease leads to rectal stenosis. STUDY FUNDING/COMPETING INTEREST: The North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) is financed by the G4 Group (The University Hospitals of Rouen, Lille, Amiens and Caen). No financial support was specifically received for this study. The authors declare no conflict of interest.

Long term efficacy of gastric electrical stimulation in intractable nausea and vomiting.

BACKGROUND: Although the efficacy of gastric electrical stimulation has been reported in short-term studies, there is a lack of data on the long-term improvement of nausea and vomiting by gastric electrical stimulation in patients with delayed or normal gastric emptying. METHODS: Thirty-one patients were implanted at our centre for medically refractory severe and chronic nausea and/or vomiting. Patients were evaluated at baseline, 6 months then 5 years after implantation (mean follow-up 80±4 months) using a symptomatic and quality of life scores. KEY RESULTS: Amongst the 31 patients, 4 were lost to follow-up, 6 explanted due to lack of improvement, and 1 patient died. Out of the 20 patients evaluated over 5 years, the quality of life score showed 27% improvement (p<0.01), including nausea (62%; p<0.01), vomiting (111%; p=0.03), satiety (158%; p<0.01), bloating (67%; p<0.01) and epigastric pain (43%; p=0.03). Over 5 years, 15/20 patients reported a 50% improvement with a global satisfaction rated at 64±6%. Therefore, 15/27 patients (56%) were improved by gastric electrical stimulation over 5 years in intention to treat. Improvement of nausea 6 months after implantation was predictive of 5-year success of gastric electrical stimulation (p=0.04). Finally, patients with delayed gastric emptying or with normal gastric emptying rate before surgery were similarly improved over 5 years (60% versus 50% respectively). CONCLUSION: Gastric electrical stimulation is safe and effective in the long term in patients with medically refractory nausea and vomiting, with an efficacy over 50% beyond 5 years in intention to treat. Gastric emptying measured before implantation did not influence the response rate over 5 years.

Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

BACKGROUND & AIMS: Gastric electrical stimulation (GES) is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD) in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation), while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10), the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.