Colonic Motor Activity Research Articles

Characteristics of the Cajal interstitial cells and intestinal microbiota in children with refractory constipation

BackgroundChildren with refractory constipation experience intense and persistent symptoms that greatly diminish their quality of life. However, the underlying pathophysiological mechanism responsible for this condition remains uncertain. Our objective was to evaluate characteristics of colonic motor patterns and interstitial cells of Cajal (ICCs) to refractory constipation children, as well as intestinal microbiota compositions. MethodsColonic manometry (CM) was conducted on a cohort of 30 patients with refractory constipation to assess colonic motility, and 7 of them underwent full-thickness colon biopsy specimens. Another 5 colonic specimens from nonconstipation patients were collected to identify the ICCs by immunohistochemistry. Fecal samples from 14 children diagnosed with refractory constipation and subjecting 28 age-matched healthy children to analysis using high-throughput sequencing of 16S rRNA. ResultsAccording to CM results, dividing 30 children with refractory constipation into 2 groups: normal group (n = 10) and dysmotility group (n = 20). Dysmotility subjects showed lower colonic motility. Antegrade propagating pressure waves, retrograde propagating pressure waves, and periodic colonic motor activity were common in normal subjects and rare in dysmotility subjects (32.7 ± 8.9 vs 20.7 ± 13.0/17 h, P < 0.05, 11.5 ± 2.3 vs 9.6 ± 2.3/17 h, P < 0.05, and 5.2 ± 8.9 vs 3.5 ± 6.8 cpm, P < 0.005, respectively), whereas periodic rectal motor activity was more common in dysmotility subjects (3.4 ± 4.8 vs 3.0 ± 3.1 cpm, P < 0.05). Dysmotility subjects exhibited a significantly greater number of preprandial simultaneous pressure waves compared to the normal subjects (32.3 ± 25.0 vs 23.6 ± 13.2/1 h, P < 0.005). Dysmotility subjects displayed a notable decrease in postprandial count of antegrade propagating pressure waves and high amplitude propagating pressure waves when compared to normal subjects (3.9 ± 2.9 vs 6.9 ± 3.5/1 h and 2.3 ± 1.5 vs 5.4 ± 2.9/1 h, respectively, P < 0.05). The number, distribution, and morphology of ICCs were markedly altered in refractory constipation compared children to the controls (P < 0.05). Children diagnosed with refractory constipation displayed a distinct dissimilarity in composition of their intestinal microbiota comparing with control group (P < 0.005). In genus level, Bacteroidetes represented 34.34% and 43.78% in the refractory constipation and control groups, respectively. Faecalibacterium accounted for 3.35% and 12.56%, respectively (P < 0.005). Furthermore, the relative abundances of Faecalibacterium (P < 0.005), Lachnospira (P < 0.05), and Haemophilus (P < 0.05) significantly decreased, whereas those of Parabacteroides (P < 0.05), Alistipes (P < 0.005), Prevotella_2 (P < 0.005), [Ruminococcus]_torques_group (P < 0.005), Barnesiella (P < 0.05), Ruminococcaceae_UCG-002 (P < 0.005), and Christensensenellaceae_R-7_group (P < 0.05) were markedly increased in children with refractory constipation. ConclusionsDysmotility subjects showed lower colonic motility and an impaired postprandial colonic response. The decreased number and abnormal morphology of colonic ICCs may contribute to the pathogenesis of refractory constipation. Children with refractory constipation exhibited significant variations in microbiota composition across various taxonomic levels compared to the healthy control group. Our findings contribute valuable insights into pathophysiological mechanism underlying refractory constipation and provide evidence to support the exploration of novel therapeutic strategies for affected children.

Dietary Supplement, Containing the Dry Extract of Curcumin, Emblica and Cassia, Counteracts Intestinal Inflammation and Enteric Dysmotility Associated with Obesity.

Intestinal epithelial barrier (IEB) impairment and enteric inflammation are involved in the onset of obesity and gut-related dysmotility. Dietary supplementation with natural plant extracts represents a useful strategy for the management of body weight gain and systemic inflammation associated with obesity. Here, we evaluate the efficacy of a food supplement containing the dry extract of Curcumin, Emblica and Cassia in counteracting enteric inflammation and motor abnormalities in a mouse model of obesity, induced by a high-fat diet (HFD). Male C57BL/6 mice, fed with standard diet (SD) or HFD, were treated with a natural mixture (Curcumin, Emblica and Cassia). After 8 weeks, body weight, BMI, liver and spleen weight, along with metabolic parameters and colonic motor activity were evaluated. Additionally, plasma LBP, fecal calprotectin, colonic levels of MPO and IL-1β, as well as the expression of occludin, TLR-4, MYD88 and NF-κB were investigated. Plant-based food supplement administration (1) counteracted the increase in body weight, BMI and metabolic parameters, along with a reduction in spleen and liver weight; (2) showed strengthening effects on the IEB integrity; and (3) reduced enteric inflammation and oxidative stress, as well as ameliorated the colonic contractile dysfunctions. Natural mixture administration reduced intestinal inflammation and counteracted the intestinal motor dysfunction associated with obesity.

Novel sensory trigger for gastrocolonic response.

Gastrocolonic response (GCR) is a physiologic increase in motor activity of the colon following meal ingestion. The presence of GCR, in colonic manometry (CM) studies, is used as a marker of normal colonic motor activity. Our aim was to investigate whether GCR could be induced by sensory stimulation (visual or olfactory) prior to food ingestion, and to describe the characteristics of patients with this response. We prospectively marked time of meal presence and initiation on CM tracings of patients with idiopathic constipation. We reviewed electronic medical records and normal CM studies. Presence of sensory GCR was defined as an increase by at least 25% of the baseline motility index (MI) after exposure to meal, prior to food ingestion. Manometry characteristics of patients with a sensory GCR response were compared to those without. Eighty-nine patients, (47% females, median age 9 years) met the inclusion criteria. Forty-seven (52.8%) patients had a positive sensory GCR. This cohort had a higher proportion of postprandial GCR (93.6% vs. 76.2%, p-value=0.02) and lower fasting MI (2.08 mm Hg vs. 3.54 mm Hg, p < 0.01). Thirteen (14.6%) patients who had no postprandial GCR had higher baseline MI (median of 3.69 vs. 2.46 mm Hg, p < 0.05). Visualizing or smelling food resulted in a significant increase in baseline MI in more than 50% of patients. Our findings propose a novel, alternate pathway that can induce GCR. This central sensory pathway may have clinical relevance in the diagnosis and management of patients with colonic dysmotility.

Evaluation of Chronic Constipation in Children With Autism Spectrum Disorder.

Chronic constipation occurs frequently in children with autism spectrum disorder (ASD). The primary objective was to determine whether chronic constipation is associated with a higher rate of abnormal colonic motor activity in ASD children than in non-ASD children. A secondary goal was to determine if clinical variables could identify children with ASD at risk for possessing abnormal colonic motility. A retrospective, propensity-matched, case-control study compared colonic manometry (CM) of an ASD cohort and non-ASD controls with chronic constipation. Clinical variables were evaluated as potential predictors for abnormal colonic motility. Fifty-six patients with ASD and 123 controls without the diagnosis of ASD who underwent CM were included. Propensity score resulted in 35 matched cohorts of ASD and controls. The rate of abnormal CM findings between ASD and matched controls (24% vs 20%, P = 0.78) did not differ significantly. A prediction model of abnormal CM that included ASD diagnosis, duration of constipation, and soiling achieved a sensitivity of 0.94 and specificity of 0.65. The risk for abnormal colonic motility increased 11% for every 1-year increase in duration of constipation. Odds for abnormal motility were 30 times higher in ASD children with soiling than controls with soiling (P < 0.0001). Chronic constipation does not appear to be associated with a higher rate of abnormal colonic motility in children with ASD. Clinical information of disease duration and presence of soiling due to constipation show promise in identifying patients with ASD at a greater risk for abnormal colonic motility.

Bio-impedance method to monitor colon motility response to direct distal colon stimulation in anesthetized pigs

Electrical stimulation has been demonstrated as an alternative approach to alleviate intractable colonic motor disorders, whose effectiveness can be evaluated through colonic motility assessment. Various methods have been proposed to monitor the colonic motility and while each has contributed towards better understanding of colon motility, a significant limitation has been the spatial and temporal low-resolution colon motility data acquisition and analysis. This paper presents the study of employing bio-impedance characterization to monitor colonic motor activity. Direct distal colon stimulation was undertaken in anesthetized pigs to validate the bio-impedance scheme simultaneous with luminal manometry monitoring. The results indicated that the significant decreases of bio-impedance corresponded to strong colonic contraction in response to the electrical stimulation in the distal colon. The magnitude/power of the dominant frequencies of phasic colonic contractions identified at baseline (in the range 2–3 cycles per minute (cpm)) were increased after the stimulation. In addition, positive correlations have been found between bio-impedance and manometry. The proposed bio-impedance-based method can be a viable candidate for monitoring colonic motor pattern with high spatial and temporal resolution. The presented technique can be integrated into a closed-loop therapeutic device in order to optimize its stimulation protocol in real-time.

Role of adipokines in regulation of colonic motor activity in overweight and obese individuals

The increasing proportion of the population suffering from overweight or obesity is now taking on the character of a pandemic. In the literature, there have begun to appear reports of associations in individuals with impaired colonic motility and a body mass index above 25 kg/m2. The present publication was prepared to systematize data on possible mechanisms of colonic motility disorders in overweight and obese individuals, including through changes in adipokine secretion and function. The literature search was performed in Embase, PubMed, and Google Scholar, using the key words ‘colon motility regulation’, ‘adipokines’, ‘gastrointestinal hormones’, ‘intestinal microbiota’, ‘overweight’, ‘obesity’, ‘visceral fat’.

Potential causes of the preoperative increase in the rectosigmoid cyclic motor pattern: A high-resolution manometry study.

BackgroundCyclic motor patterns (CMPs) are the most common motor pattern in the distal colon. This study used high‐resolution (HR) colonic manometry to quantify trends in distal colonic motor activity before elective colonic surgery, determine the effect of a preoperative carbohydrate load, and compare this with a meal response in healthy controls.MethodsFiber‐optic HR colonic manometry (36 sensors, 1 cm intervals) was used to investigate distal colonic motor activity in 10 adult patients prior to elective colonic surgery, 6 of whom consumed a preoperative carbohydrate drink (200 kCal). Data were compared with nine healthy volunteers who underwent HR colonic manometry recordings while fasted and following a 700 kCal meal. The primary outcome was the percentage of recording occupied by CMPs, defined as propagating contractions at 2–4 cycles per minute (cpm). Secondary outcomes included amplitude, speed, and distance of propagating motor patterns.ResultsThe occurrence of CMPs progressively increased in time periods closer to surgery (p = 0.001). Consumption of a preoperative drink resulted in significantly increased CMP occurrence (p = 0.04) and propagating distance (p = 0.04). There were no changes in amplitude or speed of propagating motor patterns during the preoperative period. The increase in activity following a preoperative drink was of similar magnitude to the colonic meal response observed in healthy controls, despite the lesser caloric nutrient load.ConclusionDistal colonic CMP increased in occurrence prior to surgery, amplified by ingestion of preoperative carbohydrate drinks. We hypothesize that anxiety, which is also known to rise with proximity to surgery, could play a contributing role.

The effect of water-soluble pristine C60 fullerene on 6-OHDA-induced Parkinson’s disease in rats

Oxidative stress is thought to be one of the mechanisms that leads to the dysfunction and degeneration of dopaminergic neurons in Parkinson’s disease pathogenesis and presumed to be underway during the prodromal phase. Therefore, therapy, which is effective against pre-motor symptoms, might be effective in preventing or delaying the development and progression of Parkinson’s disease. The aim of our study was to investigate the therapeutic efficiency of pristine C60 fullerene aqueous solution (C60FAS) during Parkinson’s disease in rats. The unilateral dopamine deficiency was induced in male Wistar rats (220–250 g) by stereotaxic microinjection of neurotoxin 6-hydroxydopamine (6-OHDA, 12 μg). C60FAS was injected to rats intraperitoneally daily for 10 days (0.65 mg/kg per day). The percentage of destroyed dopaminergic neurons was determined by the apomorphine test and by IHC staining of tyrosine hydroxylase-positive neurons in substantia nigra. We evaluated the rat body weight, the water and food intake, Open Field behavioural test, the level of biochemical antioxidant system, the activity of peritoneal macrophages. Levels of spontaneous and carbachol-stimulated colon motility were estimated by ballonographic method in vivo. C60FAS showed a positive tendency to increase the number of tyrosine hydroxylase-positive cells in the midbrain, which was associated with more profound improvement in apomorphine-rotation behaviour and slight relief of the anxiety level in Open Field test. Furthermore, C60FAS treatment increased the index of stimulated distal colon motor activity while it did not have a significant effect on water content in feces and total gastrointestinal transit time. C60FAS treatment did not affect water intake behaviour or body weight changes while it induced an increase of glutathione level and decrease activity of glutathione peroxidase in the brain as well as an increase in activity of peritoneal macrophages in 6-OHDA-Parkinson’s disease rats. These findings confirmed the potential therapeutic effectiveness of water-soluble pristine C60 fullerene in Parkinson’s disease pathogenesis, though there is ground for caution because of its systemic mild toxic effect.

Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer's Disease.

Palmitoylethanolamide (PEA), an endogenous lipid mediator, is emerging as a promising pharmacological agent in multiple neurodegenerative disorders for its anti-inflammatory and neuroprotective properties. However, its effects on enteric inflammation and colonic dysmotility associated with Alzheimer’s disease (AD) are lacking. This study was designed to investigate the beneficial effect of PEA administration in counteracting the enteric inflammation and relieving the bowel motor dysfunctions in an AD mouse model, SAMP8 mice. In addition, the ability of PEA in modulating the activation of enteric glial cells (EGCs), pivotally involved in the pathophysiology of bowel dysfunctions associated with inflammatory conditions, has also been examined. SAMP8 mice at 4 months of age were treated orally with PEA (5 mg/kg/day) for 2 months. SAMR1 animals were employed as controls. At the end of treatment, parameters dealing with colonic motility, inflammation, barrier integrity and AD protein accumulation were evaluated. The effect of PEA on EGCs was tested in cultured cells treated with lipopolysaccharide (LPS) plus β-amyloid 1–42 (Aβ). SAMP8 treated with PEA displayed: 1) an improvement of in vitro colonic motor activity, citrate synthase activity and intestinal epithelial barrier integrity and 2) a decrease in colonic Aβ and α-synuclein (α-syn) accumulation, S100-β expression as well as enteric IL-1β and circulating LPS levels, as compared with untreated SAMP8 mice. In EGCs, treatment with PEA counteracted the increment of S100-β, TLR-4, NF-κB p65 and IL-1β release induced by LPS and Aβ. These results suggest that PEA, under a condition of cognitive decline, prevents the enteric glial hyperactivation, reduces AD protein accumulation and counteracts the onset and progression of colonic inflammatory condition, as well as relieves intestinal motor dysfunctions and improves the intestinal epithelial barrier integrity. Therefore, PEA represents a viable approach for the management of the enteric inflammation and motor contractile abnormalities associated with AD.

Unique Neural Circuit Connectivity of Mouse Proximal, Middle, and Distal Colon Defines Regional Colonic Motor Patterns.

Background & AimsColonic motor patterns have been described by a number of different groups, but the neural connectivity and ganglion architecture supporting patterned motor activity have not been elucidated. Our goals were to describe quantitatively, by region, the structural architecture of the mouse enteric nervous system and use functional calcium imaging, pharmacology, and electrical stimulation to show regional underpinnings of different motor patterns.MethodsExcised colon segments from mice expressing the calcium indicator GCaMP6f or GCaMP6s were used to examine spontaneous and evoked (pharmacologic or electrical) changes in GCaMP-mediated fluorescence and coupled with assessment of colonic motor activity, immunohistochemistry, and confocal imaging. Three-dimensional image reconstruction and statistical methods were used to describe quantitatively mouse colon myenteric ganglion structure, neural and vascular network patterning, and neural connectivity.ResultsIn intact colon, regionally specific myenteric ganglion size, architecture, and neural circuit connectivity patterns along with neurotransmitter-receptor expression underlie colonic motor patterns that define functional differences along the colon. Region-specific effects on spontaneous, evoked, and chemically induced neural activity contribute to regional motor patterns, as does intraganglionic functional connectivity. We provide direct evidence of neural circuit structural and functional regional differences that have only been inferred in previous investigations. We include regional comparisons between quantitative measures in mouse and human colon that represent an important advance in showing the usefulness and relevance of the mouse system for translation to the human colon.ConclusionsThere are several neural mechanisms dependent on myenteric ganglion architecture and functional connectivity that underlie neurogenic control of patterned motor function in the mouse colon.

Optimizing Autonomic Function Analysis via Heart Rate Variability Associated With Motor Activity of the Human Colon.

The parameters of heart rate variability (HRV) can non-invasively assess some autonomic activities, and HRV is influenced by many bodily actions. Although parasympathetic activity is the primary driver of colonic propulsive activity, and sympathetic activity a major inhibitor of colonic motility, they are rarely measured and almost play no role in diagnosis of colon motor dysfunction or in standard treatments. Here we set out to optimize HRV analysis of autonomic nervous system changes related to human colon motility. The electrocardiogram and impedance were recorded in synchrony with colonic motor patterns by high-resolution manometry. Respiratory sinus arrhythmia (RSA), root mean square of successive differences of beat-to-beat intervals (RMSSD), the Baevsky Index or Sympathetic Index (SI), and the ratios of SI/RSA and SI/RMSSD were shown to indicate a marked increase in parasympathetic and withdrawal of sympathetic activity during the high-amplitude propagating pressure waves (HAPWs). Strong associations were seen with HAPWs evoked by a meal and rectal bisacodyl indicating a marked increase in parasympathetic and withdrawal of sympathetic activity during the gastrocolic reflex and the defecation reflex. When HAPWs occurred in quick succession, parasympathetic activation (RSA and RMSSD) occurred in a rhythmic fashion. Hence, during propulsive motor patterns, an overall shift in autonomic activity toward increased parasympathetic control was shown to be reflected in HRV. HRV assessment may therefore be valuable in the assessment of autonomic dysfunction related to colonic dysmotility.

Role of PGE2 in colonic motility: PGE2 attenuates spontaneous contractions of circular smooth muscle via EP4 receptors in the rat colon

Colonic motor activity is important for the formation and propulsion of feces. The production of prostaglandins (PGs) in colonic tissue is considered to play a critical role in the generation and regulation of colonic motility. In this study, we investigated the inhibitory effects of PGE2 and selective agonists of four EP receptors on the spontaneous phasic contractions, called ‘giant contractions’ (GCs), of mucosa-free circular smooth muscle strips from the rat middle colon. Neural blockade with tetrodotoxin (TTX) increased the frequency and amplitude of the GCs by about twofold. However, inhibiting PG production with piroxicam reduced the GC frequency in the presence of TTX, but did not affect the GC amplitude. In the presence of both TTX and piroxicam, exogenous PGE2 and each EP receptor agonist were cumulatively added to the tissue bath. In this setting, PGE2, the EP2 agonist ONO-AE1-259, and the EP4 agonist ONO-AE1-329, but not the EP1 agonist ONO-AE-DI-004 or the EP3 agonist ONO-AE-248, concentration-dependently reduced the GC frequency and amplitude. The PGE2-induced inhibition of GC frequency and amplitude was inhibited by the EP4 antagonist ONO-AE3-208, but not by the EP1/2 antagonist AH6809. Immunohistochemistry revealed the EP2 and EP4 receptors were localized in perinuclear sites in circular smooth muscle cells. EP2 immunoreactivity was also located in GFAP-immunoreactive enteroglia, whereas EP4 immunoreactivity was also located in HU (embryonic lethal, abnormal vision [ELAV] protein; a marker of all myenteric neurons)-immunoreactive myenteric nerve cell bodies. These results suggest that the PGs produced in the colonic tissue inhibit the GC frequency and amplitude of circular muscle in the rat middle colon, and is mediated by EP4 receptors expressed in the smooth muscle cells.

TRPA1 Channel Activation Inhibits Motor Activity in the Mouse Colon

There is a growing awareness of the role that TRP channels play in regulating sensory and motor functions in the gastrointestinal tract. In this study we used an in-vitro murine model of colonic peristaltic-like complexes (CPMCs) to evaluate the role of exogenous and endogenous TRPA1 signaling processes in regulating colonic motility. Using in-vitro recordings of intraluminal pressure to monitor the presence of CPMCs in colonic segments we performed a series of experiments on male CD1 mice (2 months of age) and found that CPMC activity was attenuated by TRPA1 agonists. Bath application of the TRPA1 antagonist HC-030031 had no effect upon basal CPMC activity whereas application of the synthetic TRPA1 agonist ASP7663 caused a reversible dose dependent decrease in CPMC frequency that was blocked by HC-030031. Cinnamaldehyde and 4-hydroxy-2-nonenal elicited long lasting decreases in CPMC frequency that were blocked by HC-030031 whereas the decreased CPMC activity invoked by AITC could not be blocked by HC-030031. Our results show that any potential mechanosensory function of TRPA1 doesn’t involve contributing to distension induced colonic motor activity and that a role for TRPA1 in the colon is through regulating motility through exogenous and endogenous agonist induced inhibitory effects.

Antibiotic exposure postweaning disrupts the neurochemistry and function of enteric neurons mediating colonic motor activity.

The period during and immediately after weaning is an important developmental window when marked shifts in gut microbiota can regulate the maturation of the enteric nervous system (ENS). Because microbiota-derived signals that modulate ENS development are poorly understood, we examined the physiological impact of the broad spectrum of antibiotic, vancomycin-administered postweaning on colonic motility, neurochemistry of enteric neurons, and neuronal excitability. The functional impact of vancomycin on enteric neurons was investigated by Ca2+ imaging in Wnt1-Cre;R26R-GCaMP3 reporter mice to characterize alterations in the submucosal and the myenteric plexus, which contains the neuronal circuitry controlling gut motility. 16S rDNA sequencing of fecal specimens after oral vancomycin demonstrated significant deviations in microbiota abundance, diversity, and community composition. Vancomycin significantly increased the relative family rank abundance of Akkermansiaceae, Lactobacillaceae, and Enterobacteriaceae at the expense of Lachnospiraceae and Bacteroidaceae. In sharp contrast to neonatal vancomycin exposure, microbiota compositional shifts in weaned animals were associated with slower colonic migrating motor complexes (CMMCs) without mucosal serotonin biosynthesis being altered. The slowing of CMMCs is linked to disruptions in the neurochemistry of the underlying enteric circuitry. This included significant reductions in cholinergic and calbindin+ myenteric neurons, neuronal nitric oxide synthase+ submucosal neurons, neurofilament M+ enteric neurons, and increased proportions of cholinergic submucosal neurons. The antibiotic treatment also increased transmission and responsiveness in myenteric and submucosal neurons that may enhance inhibitory motor pathways, leading to slower CMMCs. Differential vancomycin responses during neonatal and weaning periods in mice highlight the developmental-specific impact of antibiotics on colonic enteric circuitry and motility.

208 Neostigmine to Treat Colonic Pseudo-Obstruction in Cancer Patients

INTRODUCTION: Acute colonic pseudo-obstruction, or Ogilvie's syndrome, usually develops in patients post-operatively or during severe illness. It is defined as massive dilation of the colon without mechanical obstruction. Ogilvie's may resolve with conservative management, but frequently colonic decompression is needed to prevent bowel injury. Neostigmine is a drug used to treat Ogilvie's that can be tried prior to endoscopic decompression. It is a reversible acetylcholinesterase inhibitor, enhancing colonic motor activity. We aim to evaluate the demographics and clinical history of patients with Ogilvie's and the efficacy of neostigmine administration in treating Ogilvie's in our cancer population. METHODS: Retrospective data analysis was performed on patients from 2000 to 2018 who had colonic dilation, defined as &gt;8 cm in part of the colon on x-ray or cross-sectional imaging, and received neostigmine. RESULTS: The total number of patients in the study was 29. The mean age of patients was 66.7 years old (range: age 46.5–81.0). Of the 29 patients, 5 patients were female (17.2%). Leukemia was the primary malignancy in 10 patients (34.5%) and solid tumor in the other 19 patients (65.5%). Metastatic disease was found in 15 patients (51.7%). Recent chemotherapy was administered to 21 patients (72.4%). The average number of hospitalization days was 34.7 days (range: 2–120 days). Pan-dilation of the colon was noted in 10 patients (34.5%) and cecal dilation alone was noted in 7 patients (24.1%). The mean diameter of dilated colon segment was 10.8 cm (range 8.0–15.0 cm). Post-operative Ogilvie's was noted in 5 patients (17.2%). Active infection was identified in 18 patients (64.2%). One dose of neostigmine was required in 20 patients (71.4%) and remaining patients required 2 or 3 doses. Improvement of Ogilvie's was noted in 23 patients (79.3%) and complete resolution in 13 patients (44.8%). Colonoscopy was needed after a trial of neostigmine in 10 patients (34.5%). Bradycardia due to neostigmine was noted in 3 patients (10.3%) without other complications noted. CONCLUSION: In our study evaluating cancer patient, Ogilvie's was more common in elderly male patients with solid tumors and active infection. Metastatic disease was noted in about half of the study patients. It was most common to have pan-colonic dilation and isolated cecal dilation. Administration of neostigmine led to improvement of colonic pseudo-obstruction in the majority of patients (79.3%) with complete resolution noted in 44.8% of patients.

Electrocolonography: Non-Invasive Detection of Colonic Cyclic Motor Activity From Multielectrode Body Surface Recordings.

This work validates a novel non-invasive method to identify periods of cyclic motor activity in the colon using multichannel skin-surface electrical recordings on the lower abdominal region, termed electrocolonography (EColG). EColG recordings were made from 21 human subjects during a 3 hr meal-response study. A signal processing pipeline based on Continuous Wavelet Transform time-frequency analysis was used to quantify the spectral power in the colonic frequency band ( ≈ 2-6 cycles per minute; cpm) during the fasted and fed states. EColG identified a substantial 7.4 ± 3.5× maximum transient increase in motor activity in the fed state versus the fasted state, as well as a 38.3 ± 16.7% sustained spectral power increase in the colonic frequency band. The dominant frequency was 3.61 ± 0.49cpm, with activity localized primarily in the infraumbilical region near the (recto-)sigmoid colon segments. The colonic meal-responses identified with EColG were closely concordant with rectosigmoid motor activity previously characterized by intracolonic high-resolution manometry. This study is the first to demonstrate that body surface electrical recordings can properly identify rhythmic colonic activity stimulated by food intake. The new EColG technique is inexpensive, portable, and presents the opportunity for reliably measuring colonic motility by noninvasive means. We anticipate that EColG could be applied to monitor the progression of post-operative ileus, and more precisely diagnose abnormal colonic motor patterns in patients suffering from common functional disorders, such as irritable bowel syndrome.

Bowel decompression in the treatment of patients with acute colonic obstruction

According to literature data acute intestinal obstruction is characterized by a great number of neglected forms comprising 5–70% cases with the given pathology. A number of radiological signs in the way of Kloiber’s bowls and intestinal arches simply confirm this and testify of colon motor activity decompensation. To date there are no objective diagnostic criteria providing indications to intestinal decompression before the operation. Intestinal intubation, its types and indications to its fulfilment are based only on the experience and intuition of the operating surgeon. Aim — to define clinical efficiency of the intestinal wall impaired contractility diagnostics method in the treatment of patients with acute colonic obstruction. Medical histories analysis of 166 patients with obstructive intestinal obstruction was carried out. Assessment of intestinal motor activity compensation was carried out with the help of echographic criteria — the number of enlarged small bowel loops, intestinal lumen width, wall thickness, distance between Kerckring folds, number of peristaltic movements per minute. According to the suggested method 3 groups of patients were distinguished — with compensated motor activity (32 (19%) patients), with sub-compensated motor activity (61 (36.5%) patients) and with intestinal decompensated motor activity (73 (44.4%) patients). Wherein the greater number of patients with obstructive ileus (135 (81%) patients) got into the hospital with sub- and decompensated intestinal motor function. In the group of patients with compensated muscular tone intestinal decompression was not carried out, in the second group with sub-compensated intestinal tone decompression was carried out simultaneously in 13 (7.8%) patients, and in 9 (5.4%) a nasojunal probe was installed for 2–3 days, in the third group intestinal intubation was done in 63 (38%) patients. Post-operative mortality was 3.2%. Thus, echographic criteria allow establishing the degree of intestinal impaired motor function before the operation in patients with acute intestinal obstruction which decompression depends upon its state.

Colonic Electromechanical Abnormalities Underlying Post-operative Ileus: A Systematic and Critical Review.

Post-operative ileus (POI) is an inevitable consequence of major abdominal surgery, and may be prolonged in up to 30% of patients. Ileus is commonly presumed to result from paralysis of the GI tract, though there is little direct evidence to support this view. The aim of this review is to systematically search and critically review the literature investigating post-operative colonic electrical and mechanical activity. MEDLINE and Embase databases were systematically searched for articles investigating post-operative colonic motor or electrical activity in human patients. Nineteen original articles investigating post-operative colonic motor or electrical activity were identified. Most studies have used low-resolution techniques, with intermittent recordings of colonic motility. Numerous studies have shown that colonic electrical and motor activity does not cease routinely following surgery, but is of abnormal character for 3–6 days following laparotomy. One recent high-resolution manometry study identified hyperactive cyclic motor patterns occurring in the distal colon on the first post-operative day. Low-resolution studies have shown colonic slow waves are not inhibited by surgery, and are present even in the immediate post-operative period. Recovery of normal motility appears to occur in a proximal to distal direction and is temporally correlated with the clinical return of bowel function. No studies have investigated motility specifically in prolonged POI. Future studies should use high-resolution techniques to accurately characterise abnormalities in electrical and mechanical function underlying POI, and correlate these changes with clinical recovery of bowel function.

Preservation of the colo-anal reflex in colonic transection and post-operative Hirschsprung's disease: Potential extrinsic neural pathway.

The colo-anal reflex is a distinct reflex whereby the internal anal sphincter (IAS) relaxes in association with colonic high amplitude propagating contractions (HAPCs) in contrast to the recto-anal inhibitory reflex (RAIR), which is characterized by IAS relaxation upon rectal distension. The RAIR is mediated by the myenteric plexus and therefore absent in Hirschsprung disease. We retrospectively assessed the presence and the characteristics of the colo-anal reflex in children in whom large bowel continuity had been surgically disrupted to assess the role of the extrinsic nervous system in the reflex. High-resolution (HR) colonic manometry and HR-anorectal manometry were used to evaluate both colonic and anal motor activity in ten children with treatment-unresponsive slow transit constipation (STC), who had previously undergone left-sided colostomy formation with consequent disruption of the bowel continuity, and in two children with Hirschsprung's disease (HSCR), who had previously undergone distal colon resection followed by Duhamel pull-through. Eight children with STC, normal colonic motor activity, and preserved large bowel continuity served as a control group. The presence and characteristics of colo-anal reflex were analyzed. In the study group, all patients showed the presence of both normal HAPCs and the presence of the colo-anal reflex. In two cases of HSCR, RAIR was absent; however, both patients demonstrated a colo-anal reflex. In children with disrupted continuity of the colon and/or abnormal anal reflex, the colo-anal reflex is still preserved suggesting that it is mediated by a different pathway from the RAIR, possibly an extrinsic neural pathway.

Elobixibat, the first-in-class Ileal Bile Acid Transporter inhibitor, for the treatment of Chronic Idiopathic Constipation

ABSTRACTIntroduction: Elobixibat is the first in class ileal bile acid transporter (IBAT) inhibitor. IBAT inhibitors block ileal absorption of bile acids by: (1) interrupting the enterohepatic circulation of bile resulting in a fall in serum cholesterol and (2) increasing the delivery of bile acids into the colon. Increasing colonic bile acids causes mucosal fluid secretion and enhances colonic motor activity. Changes in colonic physiology may be useful in treating constipation.Areas covered: In this review, the author reviews the prevalence and medical cost of Chronic Idiopathic Constipation (CIC) and the heterogeneity of the CIC patient population as a complicating factor in drug development and clinical care. He also reviews the history of Bile Acid cathartics and the complex pharmacophysiology of bile therapy with fluid and electrolyte shifts, colonic motor function changes and mucosal immunologic activation. Finally, the author reviews elobixabat development and the clinical trials that demonstrate improvement in constipation.Expert opinion: The early phases of elobixibat development provide confirmation of high IBAT binding affinity which translates into the expected inhibition of enterohepatic bile acid circulation and enhanced delivery of ileal bile acids to the colon associated with expected physiological changes. Elobixibat as a treatment of CIC appears promising.