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

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

Introduction Whether intestinal dysmotility and proton pump inhibitor (PPI) use either independently or together contributes to small intestinal bacterial overgrowth (SIBO), and/or small intestinal fungal overgrowth (SIFO) is not known. Aim Investigate the role of dysmotility and PPI use in patients with persistent gastrointestinal complaints. Methods Patients with unexplained gastrointestinal symptoms and negative endoscopy/radiology tests completed a validated symptom questionnaire and underwent 24-hour ambulatory antro-duodeno-jejunal manometry (ADJM). Simultaneously, duodenal aspirate was obtained for aerobic, anaerobic and fungal culture. Dysmotility was diagnosed by (> 2): absent phase III MMC, absent/diminished postprandial response, diminished amplitude of antral/intestinal phasic activity, impaired antro-duodenal coordination. Bacterial growth ≥103 CFU/mL or fungal growth was considered evidence for SIBO/SIFO. PPI use was documented. Correlation of symptoms with presence of SIBO or SIFO were assessed. Results 150 subjects (M/F=47/103) were evaluated; 94/150 (63%) had overgrowth: 38/94 (40%) had SIBO, 24/94 (26%) had SIFO, and 32/94 (34%) had mixed SIBO/SIFO. SIBO was predominately due to Streptococcus, Enterococcus, Klebsiella, and E. coli. SIFO was due to Candida. 80/150 (53%) patients had dysmotility and 65/150 (43%) used PPI. PPI use (p=.0063) and Dysmotility (p=.0003) were independent significant risk factors (p<0.05) for overgrowth, but together did not pose additional risk. Symptom profiles were similar between those with or without SIBO/SIFO. Conclusions Dysmotility and PPI use were independent risk factors for SIBO or SIFO and were present in over 50% of subjects with unexplained gastrointestinal symptoms. Diagnosis of overgrowth requires testing because symptoms were poor predictors of overgrowth.

Background & Aims High-definition anorectal manometry (HDAM-3D) provides a topographic and 3-dimensional profile of anorectal pressure. We assessed anorectal sensori-motor function in healthy adults, the reproducibility of measurements made with HDAM-3D, 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 experts 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 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 y) had significantly lower resting (P<.01) and sustained squeeze pressures (P<.04). Dyssynergic patterns of defecation were observed in 12/18 subjects (67%) who attempted to defecate without the 60 cc rectal balloon distension and in 6/18 subjects (33%) with the 60 cc rectal balloon distension. Rest–retest values correlated, (r = 0.81) as did conclusions made by experts vs software analyses of data (r = 0.99). Conclusions Based on HDAM-3D measurements in healthy adults, anal sphincter pressures are higher in men than 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.

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient’s quality of life.

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.

Background and Aims The clinical significance of colorectal sensori-motor evaluation in patients with slow transit constipation (STC) is unclear. We investigated whether colonic manometric evaluation is useful for characterizing colonic sensorimotor dysfunction and for guiding therapy in STC. Methods 24-hour ambulatory colonic manometry was performed in 80 patients (70 females) with STC by placing a 6 sensor solid state probe, along with assessment of colonic sensation with barostat. Anorectal manometry was also performed. Manometrically, patients were categorized as having colonic neuropathy or myopathy based on gastrocolonic response, waking response and high amplitude propagated contractions (HAPC); and based on colonic sensation, as colonic hyposensitivity or hypersensitivity. Clinical response to pharmacological, biofeedback and surgical treatment was assessed at 1yr and correlated with manometric findings. Results 59% of patients had abnormal colonic manometry with features suggestive of neuropathy (26%), and myopathy (33%); 41% had normal colonic manometry. 74% patients had abnormal colonic sensation and 61% had overlapping dyssynergic defecation. Patients with neuropathy were more likely to have colonic hyposensitivity. 64% of patients with colonic myopathy or normal manometry improved with medical/biofeedback therapy when compared to 15% with colonic neuropathy (p<0.01). Selected patients with colonic neuropathy had excellent response to surgery, but many developed bacterial overgrowth. Conclusions Colonic manometry demonstrates significant colonic sensori-motor dysfunction in STC patients and reveals considerable pathophysiological heterogeneity. It can be useful for characterizing the underlying pathophysiology and for guiding clinical management in STC, especially surgery.

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