Agave tequilana Fructans Versus Psyllium plantago for Functional Constipation : Randomized Double-blind Clinical Trial.

GOAL: The aim of this study was to evaluate the efficacy of supplementation with Agave tequilana Weber blue variety fructans (Predilife) in the improvement of symptoms in functional constipation. BACKGROUND: Fiber supplementation is the first-line treatment for constipation. Fibers-like fructans have a known prebiotic effect. MATERIALS AND METHODS: A randomized, double-blind, study comparing agave fructans (AF) against psyllium plantago (PP). Four groups were randomized. Group 1: AF 5 g (Predilife), group 2: AF 10 g (Predilife), group 3: AF 5 g (Predilife)+10 g maltodextrin (MTDx), and group 4: PP 5 g+10 g MTDx. The fiber was administered once daily for 8 weeks. All fibers were similarly flavored and packaged. Patients kept their usual diet and fiber sources were quantified. Responders were defined as ≥1 complete spontaneous bowel movement from baseline to 8 weeks. Adverse events were reported. The study was registered in Clinicaltrials.gov with registration number NCT04716868. RESULTS: Seventy-nine patients were included (group 1: 21, group 2: 18, group 3: 20, and group 4: 20), of which 62 (78.4%) were women. The responders were similar across groups (73.3%, 71.4%, 70.6%, and 69%, P >0.050). After 8 weeks, all groups significantly increased complete spontaneous bowel movements, showing the greatest increase in spontaneous bowel movements in group 3 ( P =0.008). All groups improved in symptoms, stool consistency, and quality of life. Diet and fiber intake were similar between groups. Adverse events were mild and similar between groups. CONCLUSIONS: AF (Predilife) are as effective at different doses and combined with MTDx as PP and are a feasible option for the treatment of functional constipation.

Diagnostic differences in high-resolution esophageal motility in a large Mexican cohort based on geographic distribution.

High-resolution esophageal manometry [HRM] has become the gold standard for the evaluation of esophageal motility disorders. It is unclear whether there are HRM differences in diagnostic outcome based on regional or geographic distribution. The diagnostic outcome of HRM in a diverse geographical population of Mexico was compared and determined if there is variability in diagnostic results among referral centers. Consecutive patients referred for HRM during 2016-2020 were included. Four major referral centers in Mexico participated in the study: northeastern, southeastern, and central (Mexico City, two centers). All studies were interpreted by experienced investigators using Chicago Classification 3 and the same technology. A total of 2293 consecutive patients were included. More abnormal studies were found in the center (61.3%) versus south (45.8%) or north (45.2%) P < 0.001. Higher prevalence of achalasia was noted in the south (21.5%) versus center (12.4%) versus north (9.5%) P < 0.001. Hypercontractile disorders were more common in the north (11.0%) versus the south (5.2%) or the center (3.6%) P.001. A higher frequency of weak peristalsis occurred in the center (76.8%) versus the north (74.2%) or the south (69.2%) P < 0.033. Gastroesophageal junction obstruction was diagnosed in (7.2%) in the center versus the (5.3%) in the north and (4.2%) in the south p.141 (ns). This is the first study to address the diagnostic outcome of HRM in diverse geographical regions of Mexico. We identified several significant diagnostic differences across geographical centers. Our study provides the basis for further analysis of the causes contributing to these differences.

Does laparoscopic reoperation yield symptomatic improvements similar to those of primary laparoscopic Heller myotomy in achalasia patients?

BACKGROUND: Laparoscopic Heller myotomy fails in approximately 3.5% to 15% of patients. Evidence of successful laparoscopic reoperation is limited to a few studies. METHODS: This case-control study was conducted in patients who underwent laparoscopic Heller myotomy reoperation (LHM-R) from 2008 to 2016. The operative outcomes, preoperative and last follow-up manometric parameters, and symptom questionnaire results, including the Eckardt, Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) and eating assessment tool (EAT-10) scores, were obtained. The data were compared with those of patients who underwent primary laparoscopic Heller myotomy (LHM-1). RESULTS: Thirty-five patients who underwent LHM-R and 35 patients who underwent LHM-1 were included. The reasons for failure in the LHM-R patient group included incomplete myotomy (71.4%), myotomy fibrosis (25.7%) and structural alterations in fundoplication (2.9%). The follow-up duration was 34 months for the LHM-R group and 24 months for the LHM-1 group (p = 0.557). The procedure was performed by laparoscopy in 100% of the patients in the two groups. No differences were found regarding surgical morbidity (11.4% LHM-R vs. 2.9% LHM-1, p = 0.164). The symptomatic outcomes were equivalent between groups (Eckardt p = 0.063, EAT-10 p = 0.166, GERD-HRQL p = 0.075). An IRP < 15 mmHg was achieved in 100% of the LHM-R and LHM-1 patients. At the last follow-up, 82.1% of the LHM-R patients and 91.4% of the LHM-1 patients were in symptomatic remission (p = 0.271). CONCLUSION: The results achieved with LHM-R are similar to those achieved with LHM-1. Laparoscopic reoperation should be considered an effective and safe treatment after a failed Heller myotomy.

Diagnostic Utility of Carbohydrate Breath Tests for SIBO, Fructose, and Lactose Intolerance.

BACKGROUND: Unexplained bloating, gas, and pain are common symptoms. If routine tests are negative, such patients are often labeled as irritable bowel syndrome. AIMS: To determine the diagnostic utility of breath tests that assess for small intestinal bacterial overgrowth (SIBO), fructose or lactose intolerance, and the predictive value of symptoms. METHODS: Patients with gas, bloating, diarrhea, abdominal pain (≥ 6 months), and negative endoscopy and radiology tests were assessed with symptom questionnaires, glucose (75 g), fructose (25 g), or lactose (25 g) breath tests. Breath tests were categorized as positive when H2 (≥ 20 ppm) or CH4 (≥ 15 ppm) increased above baseline values or as hypersensitive when symptoms changed significantly without rise in H2/CH4 or as negative. RESULTS: 1230 patients (females = 878) underwent 2236 breath tests. The prevalence of SIBO was 33% (294/883), fructose intolerance was 34% (262/763), and lactose intolerance was 44% (260/590). Hypersensitivity was found in 16% and 9%, respectively, during fructose and lactose breath tests. Although gas (89%), abdominal pain (82%), and bloating (82%) were highly prevalent, pretest symptoms or their severity did not predict an abnormal breath test, but symptoms during the breath test facilitated diagnosis of SIBO, fructose, and lactose intolerance and hypersensitivity. CONCLUSIONS: Approximately 45% of patients with unexplained gas and bloating had SIBO, fructose, or lactose intolerance; another 9-16% had visceral hypersensitivity. Pretest symptoms were poor predictors, but symptoms during the breath tests were useful. Breath tests are safe, provide significant diagnostic yield, and could be useful in routine gastroenterology practice.

Autoimmune comorbidity in achalasia patients.

BACKGROUND AND AIM: Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD). METHODS: It was a cross-sectional and included 114 patients with idiopathic achalasia and 114 age-matched and sex-matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records. RESULTS: Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47-9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00-9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65-6.20). CONCLUSIONS: The non-negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.

Accuracy and Reproducibility of High-definition Anorectal Manometry and Pressure Topography Analyses in Healthy Subjects.

BACKGROUND & AIMS: High-definition anorectal manometry (HDAM-3D) provides a topographic and 3-dimensional profile of anorectal pressure. We assessed anorectal sensorimotor function and the reproducibility of measurements made with HDAM-3D in healthy adults, and the accuracy of data analysis by its software. METHODS: Anal sphincter pressures and rectal sensory thresholds were measured in 78 healthy subjects via placement of a 10-mm rigid probe, with 256 circumferentially arrayed pressure sensors, and a balloon in the rectum. The bearing down maneuver was assessed in a subset of 18 subjects. We compared data analyzed by an expert with findings from automated software analysis. Measurements made in a subset of 16 subjects, 2 weeks apart, were compared to determine reproducibility. RESULTS: Resting, squeezing, and sustained squeezing pressures were significantly higher in men than in women (P < .05); other parameters were similar. Desire and urgency to defecate were similar between men and women, but the maximal tolerable volume was significantly lower in women (P < .05). Older women (>50 years) had significantly lower resting (P < .01) and sustained squeeze pressures (P < .04). Dyssynergic patterns of defecation were observed in 12 of 18 subjects (67%) who attempted to defecate without the 60-mL rectal balloon distention and in 6 of 18 subjects (33%) with the 60-mL rectal balloon distention. Test-retest values correlated (r = 0.81), as did analyses made by an expert vs software analyses of data (r = 0.99). CONCLUSIONS: On the basis of HDAM-3D measurements in healthy adults, anal sphincter pressures are higher in men than in women, but sensory and other parameters are similar; older subjects have weaker sphincters. Many people were found to have dyssynergic patterns of defecation, which could be related to the probe or other technical issues, so this technique may not be suitable for assessing defecation patterns. Measurements made by HDAM-3D are reproducible, and data can be accurately analyzed by its software.

Treatment of esophageal (noncardiac) chest pain: an expert review.

BACKGROUND & AIMS: Chest pain is a common and frightening symptom. Once cardiac disease has been excluded, an esophageal source is most likely. Pathophysiologically, gastroesophageal reflux disease, esophageal dysmotility, esophageal hypersensitivity, and anxiety disorders have been implicated. However, treatment remains a challenge. Here we examined the efficacy and safety of various commonly used modalities for treatment of esophageal (noncardiac) chest pain (ECP) and provided evidence-based recommendations. METHODS: We reviewed the English language literature for drug trials evaluating treatment of ECP in PubMed, Cochrane, and MEDLINE databases from 1968-2012. Standard forms were used to abstract data regarding study design, duration, outcome measures and adverse events, and study quality. RESULTS: Thirty-five studies comprising various treatments were included and grouped under 5 broad categories. Patient inclusion criteria were extremely variable, and studies were generally small with methodological concerns. There was good evidence to support the use of omeprazole and fair evidence for lansoprazole, rabeprazole, theophylline, sertraline, trazodone, venlafaxine, imipramine, and cognitive behavioral therapy. There was poor evidence for nifedipine, diltiazem, paroxetine, biofeedback therapy, ranitidine, nitrates, botulinum toxin, esophageal myotomy, and hypnotherapy. CONCLUSIONS: Ideally, treatment of ECP should be aimed at correcting the underlying mechanism(s) and relieving symptoms. Proton pump inhibitors, antidepressants, theophylline, and cognitive behavioral therapy appear to be useful for the treatment of ECP. However, there is urgent and unmet need for effective treatments and for rigorous, randomized controlled trials.

Translumbar and transsacral magnetic neurostimulation for the assessment of neuropathy in fecal incontinence.

BACKGROUND: Neurologic dysfunction causes fecal incontinence, but current techniques for its assessment are limited and controversial. OBJECTIVE: The purpose of this work was to investigate spino-rectal and spino-anal motor-evoked potentials simultaneously using lumbar and sacral magnetic stimulation in subjects with fecal incontinence and healthy subjects and to compare motor-evoked potentials and pudendal nerve terminal motor latency in subjects with fecal incontinence. DESIGN: This was a prospective, observational study. SETTINGS: The study took place in 2 tertiary care centers. PATIENTS: Subjects included adults with fecal incontinence and healthy subjects. INTERVENTIONS: Translumbar and transsacral magnetic stimulations were performed bilaterally by applying a magnetic coil to the lumbar and sacral regions in 50 subjects with fecal incontinence (1 or more episodes per week) and 20 healthy subjects. Both motor-evoked potentials and pudendal nerve terminal motor latency were assessed in 30 subjects with fecal incontinence. Stimulation-induced, motor-evoked potentials were recorded simultaneously from the rectum and anus with 2 pairs of bipolar ring electrodes. MAIN OUTCOME MEASURES: Latency and amplitude of motor-evoked potentials after lumbosacral magnetic stimulation and agreement with pudendal nerve terminal motor latency were measured. RESULTS: When compared with control subjects, 1 or more lumbo-anal, lumbo-rectal, sacro-anal, or sacro-rectal motor-evoked potentials were significantly prolonged (p < 0.01) and were abnormal in 44 (88%) of 50 subjects with fecal incontinence. Positive agreement between abnormal motor-evoked potentials and pudendal nerve terminal motor latency was 63%, whereas negative agreement was 13%. Motor-evoked potentials were abnormal in more (p < 0.05) subjects with fecal incontinence than pudendal nerve terminal motor latency, in 26 (87%) of 30 versus 19 (63%) of 30, and in 24% of subjects with normal pudendal nerve terminal motor latency. There were no adverse events. LIMITATIONS: Anal EMG was not performed. CONCLUSIONS: Translumbar and transsacral magnetic stimulation-induced, motor-evoked potentials provide objective evidence for rectal or anal neuropathy in subjects with fecal incontinence and could be useful. The test was superior to pudendal nerve terminal motor latency and appears to be safe and well tolerated.

Brain and gut interactions in irritable bowel syndrome: new paradigms and new understandings.

Irritable bowel syndrome (IBS) is characterized by abdominal pain and altered bowel habits. Visceral hypersensitivity is believed to be a key underlying mechanism that causes pain. There is evidence that interactions within the brain and gut axis (BGA), that involves both the afferent-ascending and the efferent-descending pathways, as well as the somatosensory cortex, insula, amygdala, anterior cingulate cortex, and hippocampus, are deranged in IBS showing both the activation and inactivation. Clinical manifestations of IBS such as pain, altered gut motility, and psychological dysfunction may each be explained, in part, through the changes in the BGA, but there is conflicting information, and its precise role is not fully understood. A better understanding of the BGA may shed more knowledge regarding the pathophysiology of IBS that in turn may lead to the discovery of novel therapies for this common disorder.

Esophageal hypomotility and spastic motor disorders: current diagnosis and treatment.

Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis, either from a reduction or absence of contractions, whereas spastic motor disorders (SMD) are characterized by an increase in the vigor and/or propagation velocity of esophageal body contractions. Their pathophysiology is not clearly known. The reduced excitation of the smooth muscle contraction mediated by cholinergic neurons and the impairment of inhibitory ganglion neuronal function mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent clinical manifestations for both of these dysfunctions, and gastroesophageal reflux disease (GERD) is commonly associated with these motor disorders. The introduction of high-resolution manometry (HRM) and esophageal pressure topography (EPT) has significantly enhanced the ability to diagnose EH and SMD. Novel EPT metrics in particular the development of the Chicago Classification of esophageal motor disorders has enabled improved characterization of these abnormalities. The first step in the management of EH and SMD is to treat GERD, especially when esophageal testing shows pathologic reflux. Smooth muscle relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors) and pain modulators may be useful in the management of dysphagia or pain in SMD. Endoscopic Botox injection and pneumatic dilation are the second-line therapies. Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may be considered in highly selected cases but lack evidence.

The effect of voluntary pharyngeal swallowing maneuvers on esophageal swallowing physiology.

The purpose of our study was to evaluate whether swallowing maneuvers designed to impact pharyngeal physiology would also impact esophageal physiology. Healthy volunteers underwent high-resolution manometry while performing three randomized swallowing maneuvers with and without a 5-ml bolus: normal swallowing, Mendelsohn maneuver, and effortful swallowing. We examined esophageal parameters of peristaltic swallows, hypotensive or failed swallows ("nonperistaltic swallows"), distal contractile integral (DCI), contractile front velocity (CFV), intrabolus pressure, and transition zone (TZ) defect. Four females and six males (median age 39 years; range 25-53) were included in the study. The overall number of nonperistaltic swallows was 21/40 (53 %) during normal swallowing, 27/40 (66 %) during the Mendelsohn maneuver, and 13/40 (33 %) during effortful swallowing. There were significantly more overall nonperistaltic swallows with the Mendelsohn maneuver compared with effortful swallowing (p = 0.003). While swallowing a 5-ml bolus, there were more nonperistaltic swallows during the Mendelsohn maneuver (12/20, 60 %) compared to that during normal swallowing (6/20, 30 %) (p = 0.05) and more peristaltic swallows during effortful swallowing as compared to Mendelsohn maneuver (p = 0.003). Intrabolus esophageal pressure was greater during the Mendelsohn maneuver swallows in the bolus-swallowing condition as compared to normal swallowing (p = 0.02). There was no statistical difference in DCI, CFV, or TZ defect between swallowing conditions. The Mendelsohn maneuver may result in decreased esophageal peristalsis while effortful swallowing may improve esophageal peristalsis. Because it is important to understand the implications for the entire swallowing mechanism when considering retraining techniques for our patients, further investigation is warranted.

Achalasia alters physiological networks depending on sex.

Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. While the infection is eventually resolved, genetically susceptible individuals may still be at risk of developing achalasia. This study aimed to determine whether immunological and physiological networks differ between male and female patients with achalasia. This cross-sectional study included 189 preoperative achalasia patients and 500 healthy blood donor volunteers. Demographic, clinical, laboratory, immunological, and tissue biomarkers were collected. Male and female participants were evaluated separately to determine the role of sex. Correlation matrices were constructed using bivariate relationships to generate complex inferential networks. These matrices were filtered based on their statistical significance to identify the most relevant relationships between variables. Network topology and node centrality were calculated using tools available in the R programming language. Previous occurrences of chickenpox, measles, and mumps infections have been proposed as potential risk factors for achalasia, with a stronger association observed in females. Principal component analysis (PCA) identified IL-22, Th2, and regulatory B lymphocytes as key variables contributing to the disease. The physiological network topology has the potential to inform whether a localized injury or illness is likely to produce systemic consequences and the resulting clinical presentation. Here we show that immunological involvement in achalasia appears localized in men because of their highly modular physiological network. In contrast, in women the disease becomes systemic because of their robust network with a larger number of inter-cluster linkages.

A Higher Manometric Esophageal Length to Height Ratio in Achalasia Explains the Lower Prevalence of Hiatal Hernia.

Background/Aims: The evidence suggests that a shorter esophageal length (EL) in gastroesophageal reflux disease (GERD) patients is associated with the presence of hiatal hernia (HH). However, there are no reports of this association in patients with achalasia. The aim is to (1) determine the prevalence of hiatal hernia in achalasia patients, (2) compare achalasia EL with GERD patients and healthy volunteers (HV), (3) measure achalasia manometric esophageal length to height (MELH) ratio, and (4) determine if there are differences in symptoms between patients with and without hiatal hernia. Methods: This retrospective and cross-sectional study consist of 87 pre-surgical achalasia patients, 22 GERD patients, and 30 HV. High-resolution manometry (HRM), barium swallow, and upper endoscopy were performed to diagnose HH. The EL and MELH ratio were measured by HRM. Symptoms were assessed with Eckardt, Eating Assessment Tool, and GERD-health-related quality of life questionnaires. Results: The HH in GERD's prevalence was 73% vs 3% in achalasia patients (P < 0.001). Achalasia patients had a longer esophagus and a higher MELH ratio than HV and GERD patients (P < 0.001). GERD patients had a lower MELH ratio than HV (P < 0.05). EAT-10 (P < 0.0001) and Eckardt (P < 0.05) scores were higher in achalasia without HH vs HH. Conclusions: The prevalence of HH in achalasia is significantly lower than in GERD. The longer EL and the higher MELH ratio in achalasia could explain the lower prevalence of HH. Despite the low prevalence of HH in achalasia patients, the surgeon should be encouraged not to rule out HH since the risk of postoperative reflux may increase if this condition is not identified and corrected.

Is the Sars-CoV-2 virus a possible trigger agent for the development of achalasia?

BACKGROUND: Achalasia is an autoimmune disease whose probable causal agent is a neurotropic virus that chronically infects the myenteric plexus of the esophagus and induces the disease in a genetically susceptible host. The association between achalasia and coronaviruses has not been reported. AIMS: To evaluate the presence of the SARS-CoV-2 virus, the ACE2 expression, the tissue architecture, and immune response in the lower esophageal sphincter muscle (LESm) of achalasia patients who posteriorly had SARS-CoV-2 (achalasia-COVID-19) infection before laparoscopic Heller myotomy (LHM) and compare the findings with type II achalasia patients and transplant donors (controls) without COVID-19. METHODS: The LESm of 7 achalasia-COVID-19 patients (diagnosed by PCR), ten achalasia patients, and ten controls without COVID-19 were included. The presence of the virus was evaluated by in situ PCR and immunohistochemistry. ACE2 receptor expression and effector CD4 T cell and regulatory subsets were determined by immunohistochemistry. KEY RESULTS: Coronavirus was detected in 6/7 patients-COVID-19. The SARS-CoV-2 was undetectable in the LESm of the achalasia patients and controls. ACE2 receptor was expressed in all the patients and controls. One patient developed achalasia type II post-COVID-19. The percentage of Th22/Th17/Th1/pDCreg was higher in achalasia and achalasia-COVID-19 pre-HLM vs. controls. The Th2/Treg/Breg cell percentages were higher only in achalasia vs. controls. CONCLUSION & INFERENCES: SARS-CoV2 and its receptor expression in the LESm of achalasia patients who posteriorly had COVID-19 but not in the controls suggests that it could affect the myenteric plexus. Unlike achalasia, patients-COVID-19 have an imbalance between effector CD4 T cells and the regulatory mechanisms.

Diagnostic Strategy and Tools for Identifying Defecatory Disorders.

This article reviews the indications, techniques, interpretation, strengths, and weaknesses of tests (anal manometry, anal surface electromyography, rectal balloon expulsion test, barium and MRI defecography, assessment of rectal compliance and sensation, and colonic transit) that are used diagnose defecatory disorders in constipated patients. The selection of tests and the sequence in which they are performed should be individualized to and interpreted in the context of the clinical features. Because anorectal functions are affected by age, results should be interpreted with reference to age- and sex-matched normal values for the same technique.

Barostat or syringe-assisted sensory biofeedback training for constipation with rectal hyposensitivity: A randomized controlled trial.

BACKGROUND: Rectal hyposensitivity (RH) is a well-known pathophysiological dysfunction in chronic constipation. Whether biofeedback training improves RH and restores bowel function is unknown. AIM: To investigate the efficacy of barostat-assisted sensory training (BAST) with syringe-assisted sensory training (SAST) in patients with RH in a randomized controlled trial. METHODS: Patients with RH and chronic constipation (Rome III) were randomized to receive 6 biweekly sessions of BAST or SAST. Verbal/visual feedback was provided during repeated rectal distensions to improve defecation desire/urge and first sensations with either 10-cm balloon connected to barostat (BAST) or 4-cm balloon connected to syringe and manometry probe (SAST). Sensory thresholds, bowel symptoms, and therapist and patient's rating of treatments were compared. The primary outcome (responders) was the improvement in ≥2 sensory thresholds. RESULTS: Sixty-six patients were enrolled: 32 received BAST, 34 received SAST, and 56 completed study. There were significantly more responders in BAST group than SAST (78% vs. 53%, p = 0.0320). Rectal sensation normalized in 81% with BAST compared to 56% with SAST (p = 0.0270). When compared to baseline, desire and urge to defecate thresholds and bowel satisfaction improved with BAST (p = 0.0013; p = 0.0002; p = 0.0001) and SAST (p = 0.0012; p = 0.0001; p < 0.0001) and number of complete spontaneous bowel movements with BAST (p = 0.0029) but without inter-group differences. Therapists rated BAST as superior to SAST (p < 0.0001), but patients rated both equally. CONCLUSIONS: Sensory biofeedback training was effective and significantly improved rectal sensation and constipation symptoms. Although both techniques were useful, the novel BAST was more efficacious and easier to administer for treating RH.

Autoantigen characterization in the lower esophageal sphincter muscle of patients with achalasia.

BACKGROUND: Serum anti-myenteric autoantibodies define autoimmune achalasia and tissue MMP-9 activity may locally process autoantigenic proteins in the muscle of the lower esophageal sphincter (LES) of achalasia patients. METHODS: Biopsies of the LES muscle from 36 achalasia patients, 6 esophagogastric junction outflow obstruction (EGJOO) patients, and 16 transplant donors (TD) were compared in a blind cross-sectional study. Histological characteristics such as inflammation, fibrosis, presence of ganglion cells, cells of Cajal, GAD65, PNMA2, S-100, P substance, and MMP-9 proteoforms in tissue were assessed by H&E and Picrosirius Red staining and immunohistochemistry analysis. Anti-neuronal antibodies, onconeural antigens, recoverin, SOX-1, titin, zic4, GAD65, and Tr were evaluated by immunoblot/line assay. KEY RESULTS: Tissue of achalasia patients had heterogeneous inflammatory infiltrates with fibrosis and contrasting higher levels of activated MMP-9, as compared with EGJOO and TD. Moreover, lower ganglion cell percentages and cell of Cajal percentages were determined in esophageal tissues of achalasia patients versus TD. The tissues of achalasia versus EGJOO patients had higher GAD65 and PNMA2 protein expression. Unexpectedly, these proteins were absent in TD tissue. S-100 and P substance had similar expression levels in tissues of achalasia patients versus TD and EGJOO. Most of the achalasia sera had anti-GAD65 (83%) and anti-PNMA2 (90%) autoantibodies versus EGJOO (17% and 33%, respectively) and healthy volunteers (10% and 0%, respectively). CONCLUSIONS AND INFERENCES: Tissue-specific ectopic expression of GAD65 and PNMA/Ta2 and active MMP-9, associated with the presence of specific autoantibodies directed against these proteins, might participate in the pathophysiology of achalasia triggering and/or perpetuating autoimmune disease.

Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia.

Background: Episodic angina-like retrosternal pain is a prevalent symptom for achalasia patients pre- and post-treatment. The cause of postoperative chest pain remains poorly understood. Moreover, there are no reports on their predictive value for chest pain in the long-term post-treatment. The effect of laparoscopic Heller myotomy (LHM) and fundoplication techniques (Dor vs. Toupet) is unclear. Methods: We analyzed a cohort of 129 achalasia cases treated with LHM and randomly assigned fundoplication technique. All the patients were diagnosed with achalasia by high-resolution manometry (HRM). Patients were followed up at 1-, 6-, 12-, and 24-month post-treatment. We implemented unadjusted and adjusted logistic regression analyses to evaluate the predictive significance of pre- and post-operative clinical factors. Results: Preoperative chest pain with every meal was associated with an increased risk of occasional postoperative chest pain [unadjusted model: odds ratio (OR) = 12, 95% CI: 2.2-63.9, P = 0.006; adjusted model: OR = 26, 95% CI: 2.6-259.1, P = 0.005]. In type II achalasia, hypercontraction was also associated with an increased risk of chest pain (unadjusted model: OR = 2.6 e9 in all the patients). No significant differences were associated with age, type of achalasia, dysphagia, esophageal shape, and integrated relaxation pressure (IRP) with an increased risk of occasional postoperative chest pain. Also, there was no significant difference between fundoplication techniques or surgical approaches (e.g., length of myotomy). Conclusion: Preoperative chest pain with every meal was associated with a higher risk of occasionally postoperative chest pain.

Does HLA-DR7 differentiate the overlap syndrome of auto-immune hepatitis-primary biliary cirrhosis (AIH-PBC) from those with auto-immune hepatitis type 1?

INTRODUCTION: Autoimmune hepatitis (AIH) and overlap-syndrome (OS) are autoimmune liver diseases of unknown etiology. Although HLA-DR3/DR4 plays a susceptibility role in AIH but there is limited information in regard to OS. OBJECTIVE: Determine the genetic expression of HLA-DR among patients with AIH versus OS in order to establish susceptibility alleles in comparison to healthy controls (HC). METHODS: 26 patients with AIH and 15 patients with OS were studied. Ninety-nine healthy historical controls without autoimmunity were evaluated. Patients with AIH and OS were selected based on the international group for the study of AIH criteria and the Chazouilleres criteria for OS. Patients had at least one liver biopsy. Characterization of HLA-DR was extracted from peripheral blood leukocytes. Alleles were obtained for AIH, OS and HC and comparisons were made between groups. RESULTS: There was a significant increase in HLADR3 and DR1 in AIH compared with the HC group (p = 0.04, OR 2.6, 0.87-7.9, 95% CI). In the AIH group there was a decreased frequency in allele HLA-DR8 when compared with HC (p = 0.04, OR 3.2). There were no statistical differences between the genetic frequencies in the OS group compared with HC. However, HLA-DR7 was able to distinguish between OS patients from those with AIH (p = 0.02, OR 9.8, 1.02-233.6, 95% CI). CONCLUSIONS: HLA-DR1/DR3 is increased in AIH, but contrary to data reported in AIH, HLA-DR7 frequency is increased in OS, suggesting increased susceptibility which distinguishes patients with AIH from those with OS.