Gastric motility disorders and their endoscopic and surgical treatments other than bariatric surgery.

Gastroparesis is the most common gastric motility disorder. The cardinal symptoms are nausea, vomiting, gastric fullness, early satiety, or bloating, associated with slow gastric emptying in the absence of mechanical obstruction. Delayed gastric emptying is demonstrated by a gastric emptying scintigraphy or by a breath test. Gastroparesis can be idiopathic, post-operative, secondary to diabetes, iatrogenic, or post-infectious. Therapeutic care must be multidisciplinary including nutritional, medical, endoscopic and surgical modes. The complications of delayed gastric emptying must be sought and addressed, particularly malnutrition, in order to identify and correct vitamin deficiencies and fluid and electrolyte disturbances. An etiology should be identified and treated whenever possible. Improvement in symptoms can be treated by dietary regimes and pharmaceutical treatments, including prokinetics. If these are not effective, specialized endoscopic approaches such as endoscopic or surgical pyloromyotomy aim at relaxing the pyloric sphincter, while the implantation of an electrical stimulator of gastric muscle should be discussed in specialized centers.

Expectations of IBS patients concerning disease and healthcare providers: Results of a prospective survey among members of a French patients' association.

BACKGROUND AND AIMS: IBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients' organization. PATIENTS AND METHODS: From January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP. RESULTS: 222/330 (67%) responded (women: 68.5%, 46.5±17.7 years, disease duration: 8.8±0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS>300 in 53% and HAD score>19 in 45%). QoL impairment was correlated with disease severity and HAD score (r=-0.707 and r=-0.484, P<0.001 respectively), but not with IBS subtype. Expectations for IBS were "improved health", "better information on causes and treatments" (94%) and "better disease recognition" (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients' organization. CONCLUSIONS: French IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients' organization.

Delayed gastric emptying and altered antrum protein metabolism during activity-based anorexia.

BACKGROUND: Anorexia nervosa, a restrictive eating disorder, is often associated with gastrointestinal disorders, particularly a delayed gastric emptying. However, the mechanisms remained poorly documented. Thus, we aimed to evaluate gastric emptying and antrum protein metabolism in the Activity-Based Anorexia model (ABA). METHODS: Females C57Bl/6 mice were randomized into 3 groups: Control, ABA, and Limited Food Access (LFA). Food access has been progressively limited from 6 h/day at day 6 to 3 h/day at day 9 and until day 17. ABA mice had free access to an activity wheel. Gastric emptying was assessed. On gastric extracts, a proteomic analysis was performed, as well as an evaluation of protein synthesis and protein oxidation. KEY RESULTS: Both LFA and ABA mice exhibited a delayed gastric emptying compared with Controls (P < .05). Proteomic approach revealed 15 proteins that were differentially expressed. Among these proteins, we identified 2 clusters of interest contributing to (i) the organization of muscle fiber with ACTA2, VCL, KRT19, KRT8, and DES proteins and (ii) "heat shock proteins" with STIP1, HSPD1, and HSPA8 proteins. ABA mice specifically exhibited an increased rate of gastric oxidized proteins. CONCLUSIONS AND INFERENCES: Delayed gastric emptying observed in anorectic conditions appears to be secondary to malnutrition. However, an oxidative stress is specifically present in the stomach of ABA mice. Its role remains to be further studied.

The diagnostic value of the functional lumen imaging probe versus high-resolution anorectal manometry in patients with fecal incontinence.

BACKGROUND: The functional lumen imaging probe (EndoFLIP® ) is a new technology that measures the distensibility of the anal canal represented by the anal distensibility index. The aims of this study were (i) to compare the anal distensibility index to anal pressure in a cohort of patients with fecal incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP® to that of high-resolution anorectal manometry (HRAM) in the same cohort of patients. METHODS: Eighty-three consecutive patients with FI who underwent EndoFLIP® and HRAM assessments were enrolled. The diagnostic value of the EndoFLIP® was compared to that of HRAM and agreement between EndoFLIP® and HRAM data was assessed. KEY RESULTS: More than 70% of the patients diagnosed with anal deficiency at rest and/or during voluntary contractions by HRAM had the same diagnosis using the EndoFLIP® . Two patients with higher distensibility indexes at rest had normal anal resting pressures. Sixteen patients with a normal EndoFLIP® index (ie, normal distensibility index at rest and during voluntary contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had no sphincter lesion or neuropathic disorder that could explain an abnormal anal sphincter function. CONCLUSIONS & INFERENCES: We demonstrated that the anal distensibility index and HRAM results are largely in agreement. We did, however, identify several discrepancies between the two techniques, indicating that they may be complementary.

Are characteristics of abdominal pain helpful to identify patients with visceral hypersensitivity in irritable bowel syndrome? Results of a prospective study.

BACKGROUND: Some consider that patients with visceral hypersensitivity may represent a separate entity within the IBS population not only from a pathophysiological but also from a clinical perspective. The aim of this prospective exploratory study was to assess whether characteristics of abdominal pain in IBS patients could be suggestive of hypersensitivity. METHODS: This prospective study included consecutive IBS patients selected by Rome III criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to phenotype patients who were also asked to describe the main location of their abdominal pain on a simple image (abdomen divided into 6 zones). Progressive isobaric rectal distensions were performed to demonstrate, with the ascending method of limits, allodynia (pain threshold lower than 24 mmHg). KEY RESULTS: Fifty patients (women: 72%), 42.6 ± 15.7 years old, were included. Sub-types were IBS-D, IBS-C and IBS-M in 58%, 22% and 20% of cases, respectively. Allodynia was present in 18% of cases. Neither IBS-SSS nor intensity of pain was predictive of hypersensitivity. In hypersensitive patients, pain was more often located in one of the two iliac fossa (P = 0.02) and located outside these areas in only 11% of cases. The sensitivity and the specificity of this pain location to differentiate hyper from normosensitive patients were 0.89 and 0.59, respectively. CONCLUSIONS & INFERENCES: The location of pain is different between hyper and normosensitive IBS patients. Pain located outside one of the two iliac fossa suggests that the patient is normosensitive.

Acute sacral nerve stimulation reduces visceral mechanosensitivity in a cross-organ sensitization model.

BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model. METHODS: Hypersensitive model was obtained by instillation of acetic acid into the bladder of rats during 5 minutes, 30 minutes before the start of the experiments. Visceral sensitivity was assessed by monitoring the change in mean arterial pressure in response to graded isobaric colorectal distension series. To decipher the mechanisms underlying SNS effect, rats were administered intravenously either a nonselective opioid receptor antagonist (naloxone) or a nitric oxide synthesis antagonist (L-NAME). Neuronal activation in the dorsal horn of the sacral spinal cord was measured by counting c-fos immunoreactive cells in response to colorectal distension and NMS. KEY RESULTS: Intravesical acetic acid instillation increased mean arterial pressure variation in response to colorectal distension when compared to saline group. SNS reduced the variation in arterial pressure. Colorectal distension induced a rise in c-fos immunoreactive cells in the dorsal horn of the spinal cord. This effect was reduced by SNS. CONCLUSIONS & INFERENCES: SNS reduces visceral mechanosensitivity in a cross-organ sensitization model.

Lactose malabsorption in systemic sclerosis.

BACKGROUND: There are no studies on systemic sclerosis (SSc) assessing the relationship between food intake, especially lactose, and gastrointestinal dysfunction. AIM: To determine the prevalence of lactose malabsorption, using lactose breath test, in patients with SSc. To evaluate the correlation between lactose malabsorption and gastrointestinal involvement. To predict which SSc patients exhibit lactose malabsorption. METHODS: Seventy-seven consecutive Caucasian patients with SSc and 20 control subjects underwent lactose breath test. All patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. RESULTS: The prevalence of lactose malabsorption was higher in SSc patients than in controls (44.3% vs. 10%; P = 0.004). We observed a marked correlation between the presence of lactose malabsorption and: higher values of GSS (P < 0.0001); severe oesophageal (P = 0.018) and small intestinal (P = 0.04) motor disorders; and joint involvement (P = 0.019). Furthermore, in SSc patients with symptomatic lactose malabsorption, the median value of GSS of digestive symptoms was lower after initiation of lactose-free diet (P < 0.0001). CONCLUSIONS: Our study underscores the fact that lactose malabsorption often occurs in patients with systemic sclerosis. Furthermore, our findings highlight the fact that lactose breath test is a helpful, noninvasive method, by identifying the group of patients with systemic sclerosis with symptomatic lactose malabsorption that may benefit from a reduction in lactose intake.

Do endoflip assessments of anal sphincter distensibility provide more information on patients with fecal incontinence than high-resolution anal manometry?

BACKGROUND: Anal manometry is the standard technique for evaluating anal sphincter function. However, the functional lumen imaging probe (EndoFLIP(®) ) can be used to measure sphincter distensibility during volume-controlled distensions. Our aims were (i) to assess anal distensibility in patients with fecal incontinence (FI) and in healthy subjects using the EndoFLIP(®) and (ii) to compare the results with anal pressures measured by 3D high-resolution manometry (3D-HRM) to determine whether the EndoFLIP(®) was more sensitive and specific for diagnosing FI than 3D-HRM. METHODS: EndoFLIP(®) and 3D-HRM assessments of 34 female FI patients and 40 healthy female subjects were performed. Anal distensibility was measured as the median cross-sectional area at the narrowest point divided by the corresponding intra-bag pressure at rest and during peak voluntary contraction and was expressed in mm(2) /mmHg. KEY RESULTS: A 40-mL anal distensibility index was selected for further comparisons as it provided the best discrimination between the FI patients and the healthy subjects. The index was significantly higher in the FI patients than in the healthy subjects at rest (p = 1.10(-4) ) and during voluntary contraction (p = 1.10(-4) ). The index at rest and during voluntary contraction appeared to be more appropriate than anal pressures for discriminating between FI patients and healthy subjects. CONCLUSIONS & INFERENCES: The present study confirmed that FI is associated with an abnormally high distensibility index at rest and during voluntary contraction. The ability of the distensibility index to discriminate between FI patients and healthy subjects was significantly better than anal pressure.

Impact of deep brain stimulation on pharyngo-esophageal motility: a randomized cross-over study.

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinson's disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study. METHODS: Sixteen humans PD patients (4 women, 12 men; age: 62.4 ± 9.3-years old) who underwent STN stimulation for at least 6 months were randomly evaluated with either stimulator turned OFF then ON, or inversely. Esophageal high resolution manometry was performed at the end of each ON and OFF period, with a 5 min resting period followed by ten swallows of 5 mL. KEY RESULTS: During the ON, an increase in the distal contractility index was found (OFF: 1750 ± 629 vs ON: 2171 ± 755 mmHg/cm/s; p = 0.03), with no difference in the distal front velocity. A decrease in the integrative relaxation pressure of the lower esophageal sphincter (LES) was noted (OFF: 11.1 ± 1.8 mmHg vs ON: 7.2 ± 1.8 mmHg; p < 0.05) in ON. The LES resting pressure remained unchanged during the two periods. This resulted in a decrease in the intrabolus pressure (p = 0.03). No difference was observed for the upper esophageal sphincter, nor the pharyngeal contraction amplitude and velocity. CONCLUSIONS & INFERENCES: In conclusion, STN stimulation in PD patients increased esophageal body contractions and enhanced the LES opening. This suggests that the nigrostriatal-striatonigral loop is involved in the control of esophageal motility.

Acute sacral nerve stimulation reduces visceral mechanosensitivity in Rat through spinal opioid pathway.

BACKGROUND: Sacral nerve stimulation (SNS) is an alternative surgical treatment of refractory urge incontinence and/or fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS remain poorly understood. The aim of this experimental study was to evaluate the effect of SNS on visceral mechanosensitivity in rats. METHODS: Anesthetized Sprague-Dawley rats were treated with SNS or sham stimulation. SNS was performed by implanting an electrode close to the sacral nerve root S1. Rats were administered either a non-selective opioid receptor antagonist (naloxone) or a nitric oxide synthase inhibitor (L-NAME). Colonic mechanosensitivity was evaluated using the variation of arterial blood pressure as a spino-bulbar reflex in response to graded isobaric colorectal distension (CRD). C-fos immunoreactive neurons were quantified in spinal and supraspinal sites. µ-opioid receptor (MOR) internalization was counted in the sacral spinal cord with sham or effective SNS in response to CRD. KEY RESULTS: SNS reduced visceral mechanosensitivity in response to CRD. This effect was reversed by intrathecal and intraveinous naloxone administration. In both models, CRD induced increased c-fos immunoreactivity in the dorsal horn neurons of the sacral spinal cord and supraspinal areas. This increase was prevented by SNS. MOR internalization was significantly higher in stimulated group. CONCLUSIONS & INFERENCES: SNS impacts on visceral mechanosensitivity by decreasing the spino-bulbar reflex in response to CRD. Spinal opioid receptors are likely involved in this effect.

Impaired fasting pyloric compliance in gastroparesis and the therapeutic response to pyloric dilatation.

BACKGROUND: Pyloric pressure and compliance have never been investigated in health nor gastroparesis. AIM: We hypothesised that pyloric pressure and/or compliance may be altered in gastroparesis. METHODS: Fasting pyloric pressure and compliance were investigated in 21 healthy volunteers (HV), 27 gastroparetic patients (GP) and 5 patients who had undergone oesophagectomy without pyloroplasty as positive controls. Under videofluoroscopic control, pyloric compliance and pressure were measured by the EndoFLIP technique. Gastric emptying half time (T1/2 ) using (13) C-octanoic acid breath test, as well as symptoms and quality of life (GIQLI score) were also monitored. RESULTS: Mean fasting pyloric compliance was measured at 25.2 ± 2.4 mm²/mmHg in HV, and was lower both in GP (16.9 ± 2.1 mm²/mmHg; P < 0.05) and patients with oesophagectomy (10.9 ± 2.9 mm²/mmHg; P < 0.05). By contrast, fasting pyloric pressure was not different among groups. Fasting pyloric compliance and pressure correlated with T1/2 in GP (R = -0.43; P = 0.04). Fasting pyloric compliance, but not pressure, correlated with symptoms and GIQLI score. Pyloric dilation in 10 GP with low fasting pyloric compliance (<10 mm²/mmHg) increased compliance from 7.4 ± 0.4 to 20.1 ± 4.9 mm²/mmHg (P < 0.01) and improved the GIQLI score from 72.5 ± 5.5 to 89.3 ± 6.1 (P = 0.04). CONCLUSION: This prospective study assessed pyloric compliance for the first time, and showed that fasting pyloric compliance is decreased in gastroparetic patients and is associated with T1/2 , symptoms and quality of life. This suggests that pyloric compliance may be a new relevant metric in gastroparetic patients, and may be useful to target patients for pyloric dilation or botulinum toxin injection.

Can multichannel intraluminal pH-impedance monitoring be limited to 3 hours? Comparison between ambulatory 24-hour and post-prandial 3-hour recording.

Esophageal multichannel intraluminal pH-impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post-prandial 3-hour recording could predict the results obtained in ambulatory 24-hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post-prandial 3-hour MII was recorded after a test meal, then followed by ambulatory 21-hour MII. Correlation between the total number of liquid reflux events in the 3-hour and 24-hour recordings was elevated (R=0.71; P<0.001), with better correlation for acid (R=0.80; P<0.001) and weak acid reflux (R=0.56; P<0.001) than non-acid reflux (R=0.44; P<0.01). Sensitivity and specificity of 3-hour recording in detecting elevated liquid reflux over 24 hours (id>75reflux/24 h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3-hour post-prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24-hour MII recording.

Effect of transcranial magnetic stimulation on rectal sensitivity in irritable bowel syndrome: a randomized, placebo-controlled pilot study.

AIM: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. METHOD: In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0 ± 12.6 years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5 days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. RESULTS: There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. CONCLUSION: This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.

Evoked pressure curves from the external anal sphincter following transcranial magnetic stimulation in healthy volunteers and patients with faecal incontinence.

AIM: The hypothesis was tested that evoked pressure curves (EPCs) after transcranial magnetic stimulation (TMS) would provide additional neuropathophysiological information on the descending pathways to the external anal sphincter (EAS) in patients with faecal incontinence (FI). METHOD: Twenty-five healthy subjects and 69 patients with FI were investigated. TMS was applied to the vertex, and EPCs were recorded with a probe placed through the EAS. TMS was performed with the EAS at rest and during contraction (facilitated responses). At least three responses were recorded for each modality. Clinical data and anorectal manometric, electrophysiological perineal and transanal ultrasound recordings were compared with respect to the EPC results. RESULTS: There was no statistically significant difference between the EPCs of healthy subjects and FI patients. Twenty-three per cent of the FI patients had abnormal EPC latencies, with significantly lower voluntary contraction amplitudes (P = 0.03) and significantly higher rectal sensation (P = 0.04) than the other group. We found no significant difference between FI patients with and without abnormal EPC latencies in terms of clinical characteristics and electrophysiological and endoanal ultrasound parameters. There was no difference in the identified causes of the FI between the two groups. CONCLUSION: As abnormal EPC latencies were found in 23% of FI patients with no known central neurological disease, abnormal EPC latencies might reveal undetected lesions of descending pathways in patients with FI.

Influence of gastric emptying on gastro-esophageal reflux: a combined pH-impedance study.

BACKGROUND: The involvement of delayed gastric emptying (GE) in the pathophysiology of gastro-esophageal reflux disease (GERD) remains debated and has been to date only assessed using esophageal pH-metry that only detects acidic reflux. We therefore investigated whether delay in GE could impact on liquid, mixed, and gas reflux detected using combined esophageal pH-impedance recording. PATIENTS AND METHODS: Thirty consecutive patients were explored with GE and esophageal pH-impedance measurement in the workup of typical symptoms of GERD. Gastric emptying was assessed using the (13) C-octanoic acid breath test and an ambulatory esophageal pH-impedance recording was performed off proton pump inhibitors (PPIs) for 24 h. KEY RESULTS: Gastric emptying was normal in 17 patients and delayed in 13 patients. Delay in GE increased the daily number of liquid/mixed reflux events detected by combined esophageal pH-impedance monitoring, but had no effect of esophageal acid exposure or gas reflux. This translated in increased number of postprandial reflux events, with a longer bolus clearance time and increased esophageal proximal extension. In patient with delayed GE, symptomatic reflux had a higher proximal extension and a longer bolus clearance time compared to symptomatic reflux events from patients with normal GE. CONCLUSIONS & INFERENCES: Delay in GE increases daily and postprandial liquid/mixed reflux events. Reflux characteristics differently trigger symptoms in patients with normal and delayed GE, and may impact on the therapeutic strategy.

Transcutaneous electrical tibial nerve stimulation in the treatment of fecal incontinence: a randomized trial (CONSORT 1a).

OBJECTIVES: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials. METHODS: In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events. RESULTS: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P=0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P=0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b). CONCLUSIONS: We failed to demonstrate any benefit of TENS on our primary end-point.