Enrique Coss-Adame

Clinical utility of colonic manometry in slow transit constipation

The clinical significance of colorectal sensorimotor 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.

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.

Diagnostic utility of the oesophageal balloon distension test in the evaluation of oesophageal chest pain

Oesophageal balloon distension test (EBDT) has been advocated for the evaluation of functional oesophageal noncardiac chest pain (NCCP), but its diagnostic utility remains unclear.

Evaluation of constipation in older adults: Radioopaque markers (ROMs) versus wireless motility capsule (WMC)

There is scarce information regarding assessment of constipation in older subjects. We examined regional and whole-gut transit time (WGTT) with wireless motility capsule (WMC) and compared this with radioopaque markers (ROM) transit. 39 constipated and 11 healthy older subjects (≥ 65 years) ingested a ROM capsule and WMC, wore a data receiver and kept stool diaries for 5 days. WMC recordings were analyzed for colonic transit time (CTT), WGTT and gastric emptying time (GET). Radiographs obtained on day 5 assessed ROM transit. Results for each device were compared. The CTT (p = <0.0001), WGTT (p = <0.001) and GET (p = <0.04) as measured by WMC were all slower in constipated subjects compared to healthy subjects. ROM colonic transit was also slower (p = <0.007) in constipated compared to healthy subjects. The diagnostic utility for identifying subjects with constipation as assessed by receiver operating characteristics were similar; 0.85 (WMC) versus 0.73 (ROM). Device agreement for slow colonic transit was 88% with good correlation between WMC and ROM (CTT r=0.718, p=0.0001, WGTT r=0.693, p=0.0001). Slow transit constipation was identified in 28% with ROM and 32% with WMC. No adverse events were recorded. WMC is a safe and useful device that provides objective diagnosis of delayed colonic and whole gut transit in older constipated adults. It is a radiation-free, physiologic and ambulatory technique that provides additional diagnostic information than ROM.

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.

New insights into the pathophysiology of achalasia and implications for future treatment

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.

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.

Autoimmune comorbidity in achalasia patients

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).

Consenso mexicano sobre estreñimiento crónico

INTRODUCTION Significant advances have been made in the knowledge and understanding of the epidemiology, pathophysiology, diagnosis, and treatment of chronic constipation, since the publication of the 2011 guidelines on chronic constipation diagnosis and treatment in Mexico from the Asociación Mexicana de Gastroenterología. AIMS To present a consensus review of the current state of knowledge about chronic constipation, providing updated information and integrating the new scientific evidence. METHODS Three general coordinators reviewed the literature published within the time frame of January 2011 and January 2017. From that information, 62 initial statements were formulated and then sent to 12 national experts for their revision. The statements were voted upon, using the Delphi system in 3 voting rounds (2 electronic and one face-to-face). The statements were classified through the GRADE system and those that reached agreement >75% were included in the consensus. RESULTS AND CONCLUSIONS The present consensus is made up of 42 final statements that provide updated knowledge, supplementing the information that had not been included in the previous guidelines. The strength of recommendation and quality (level) of evidence were established for each statement. The current definitions of chronic constipation, functional constipation, and opioid-induced constipation are given, and diagnostic strategies based on the available diagnostic methods are described. The consensus treatment recommendations were established from evidence on the roles of diet and exercise, fiber, laxatives, new drugs (such as prucalopride, lubiprostone, linaclotide, plecanatide), biofeedback therapy, and surgery.

Histopathologic patterns among achalasia subtypes.

Sir: We read with interest the recent manuscript by Sodikoff et al. entitled ‘Histopathologic patterns among achalasia subtypes’. This study is focused on Histopathologic patterns and its correlation with manometric subtypes of achalasia. Although we see with satisfaction the results obtained in this manuscript since most of them agree with those previously published by our research group, we would like to make some relevant observations. Six months ago, our group demonstrated the inflammatory pattern regarding manometric subtypes of achalasia. It is noteworthy that in the study published by Sodikoff et al., only 17% of patients have inflammation and even three biopsies resemble normal tissue in contrast with our findings that show inflammation in 100% of the cases. This probably can be explained based on the study approach for evaluating inflammation. The method that they used was not very sensitive and it is only limited to determine the percentage of CD3, CD4, and CD8. We evaluated inflammation from various aspects, including pro-inflammatory cytokine‒producing cells (IL-22, IL17A, IFN-c), some extracellular matrix turnover proteins (MMP-9/TIMP-1), and pro-fibrogenic cytokine‒ producing cells (TGF-b1, IL-4, and IL-13). Moreover, regulatory T and B cells were also determined. Finally, circulating Th22, Th17, Th2, Th1, and Treg cells were immunophenotyped. We determine a statistically significant higher percentage of tissue and peripheral proand anti-inflammatory cytokine‒producing cells in type II vs type I achalasia patients. However, we found no differences in relation to Treg and Breg cells and the achalasia type. Regarding to standardized formalin-fixed and paraffin-embedded tissue in Sodikoff’s study, we must highlight that although the longterm storage (between 12 and 17 years) slightly decreases the antigenicity, the combination of storage time, storage temperature, and paraffin coating of stored slides produces a significantly decreased stain intensity. This could be the rational whereby Sodikoff et al. did not detect Foxp3 and other inflammatory markers in LES tissue, while we observed a higher percentage of CD25/Foxp3 cells in esophageal smooth muscle tissue from type III achalasia patients, followed by types I and II when compared with the control group. Another potential caveat in their study is that the manometric evaluation was performed with conventional manometry. The Chicago Classification for achalasia subtypes is based on highresolution manometry and the adaptation from conventional manometry may misclassify a small number of cases. Our study provides strong evidence of inflammation as a possible mayor factor in the pathogenesis of achalasia subtypes with the use of immunosuppressive drugs as probable future treatment for this pathology.