Current insights on chronic intestinal dysmotility: pseudo-obstruction and enteric dysmotility.

Chronic intestinal dysmotility is a rare and debilitating digestive disorder characterized by symptoms of mechanical obstruction without an organic lesion. It has diverse causes and involves various pathological mechanisms. Small bowel manometry is the preferred diagnostic method, particularly for patients with severe and progressive symptoms. The condition can be categorized as intestinal pseudo-obstruction and enteric dysmotility, both entities share abnormal small bowel motility, but with important differences in prognosis and management.

Organization of Neurogastroenterology and Motility units with a multidisciplinary, patient-centered perspective.

Neurogastroenterology and Motility is a Gastroenterology subspecialty dealing with the management of gastrointestinal (GI) motor diseases and disorders of gut-brain interaction (DGBI). Both types of conditions may impair the nutritional status of patients - In the case of motility disorders, because deficient gastrointestinal motility may impair appropriate food digestion and absorption; in DGBI because development of gastrointestinal symptoms may impair appropriate patient nutrition. In both cases, different studies have shown that patients start restrictive diets on their own, without supervision of a dietician, which leads to nutritional deficits in many cases. Likewise, psychological factors like stressful situations or anxiety may trigger gastrointestinal symptoms in these patients, mainly in those with DGBI. Recent studies comparing a patient-centered approach that includes medical treatment, dietary modifications, and behavioural interventions with gastroenterologist-only standard care have shown a greater proportion of improved symptoms, psychological status, and quality of life, as well as reduced costs in patients allocated to the multidisciplinary treatment arm. In conclusion, there is growing evidence in favour of dietary and behavioural interventions by specialized professionals, coupled with appropriate medical evaluation and treatment by a gastroenterologist. Hence the importance of developing reference units in which comprehensive, individualized management may be offered. Multidisciplinary models improve clinical outcomes and patient satisfaction, which should result in a reduction of direct and indirect costs. .

Small intestinal bacterial overgrowth. A position paper of ASENEM-SEPD.

Small intestinal bacterial overgrowth (SIBO) is a condition that was described decades ago and has recently aroused special interest among both medical professionals and the general population, likely because of increased availability of diagnostic testing and extensive coverage by the media and social networks. In view of the large amount of-often conflicting-information available, the need has arisen to develop a joint position paper of the Sociedad Española de Patología Digestiva (SEPD) and Asociación Española de Neurogastroenterología y Motilidad (ASENEM) to discuss up-to-date scientific information.

Nutritional challenges in patients with gastroparesis.

PURPOSE OF REVIEW: Our purpose was to review the most recent publications on nutritional management in gastroparesis, and their relevance for global management of gastroparesis. RECENT FINDINGS: The last months, several reviews on gastroparesis have been published as well as excellent reviews on the nutritional management of patients suffering this condition. In these publications, the relevance of nutrition in management of gastroparesis has been highlighted. However, alarming studies have been published from several authors from Europe and the United States showing that a majority of patients did not follow any dietary advice from a specialist in nutrition, most patients start restrictive diets by their own, and that as much as 60% of patients have a caloric-deficient diet. In addition, recent studies show that some of the recommendations, like a radical exclusion of fibers from the diet, may be reconsidered taking into account the potential beneficial effects of fibers in global health. SUMMARY: Nutritional interventions are one of the cornerstones in management of gastroparesis. Consequently, an interdisciplinary approach, with managing teams composed by gastroenterologist and specialist in nutrition should be the correct strategy to achieve the best outcomes in symptom control and prevention of complications related to nutritional deficits. VIDEO ABSTRACT: http://links.lww.com/COCN/A17.

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant.

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.

Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm2 with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE.NEW & NOTEWORTHY Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.

Enteric neuron density correlates with clinical features of severe gut dysmotility.

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are based mainly on classic qualitative histopathological/immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to quantify the interganglionic distance between neighboring myenteric ganglia immunoreactive for neuron-specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies/ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16-77 yr) with well-characterized severe dysmotility and 8 controls (4 females; 47-73 yr). A symptom questionnaire was filled before surgery. Mann-Whitney U test, Kruskal-Wallis coupled with Dunn's posttest and nonparametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared with controls, patients with severe dysmotility exhibited a significant increase in myenteric interganglionic distance (P = 0.0005) along with a decrease in the number of myenteric (P < 0.00001) and submucosal (P < 0.0004) neurons. A 50% reduction in the number of submucosal and myenteric neurons correlated with an increased interganglionic distance and severity of dysmotility. Our study proposes a relatively simple tool that can be applied for quantitative evaluation of paraffin sections from patients with severe dysmotility. The finding of an increased interganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an interganglionic distance within the control range.NEW & NOTEWORTHY Enteric neuropathies are challenging conditions characterized by a severe impairment of gut physiology, including motility. An accurate, unambiguous assessment of enteric neurons provided by quantitative analysis of routine paraffin sections may help to define neuropathy-related gut dysmotility. We showed that patients with severe gut dysmotility exhibited an increased interganglionic distance associated with a decreased number of myenteric and submucosal neurons, which correlated with symptoms and clinical manifestations of deranged intestinal motility.

Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders.

Prebiotics and diets low in fermentable oligo-, di-, mono-saccharides and polyols (low-FODMAP diet) might reduce symptoms in patients with functional gastrointestinal disorders, despite reports that some nonabsorbable, fermentable meal products (prebiotics) provide substrates for colonic bacteria and thereby increase gas production. We performed a randomized, parallel, double-blind study of patients with functional gastrointestinal disorders with flatulence. We compared the effects of a prebiotic supplement (2.8 g/d Bimuno containing 1.37 g beta-galactooligosaccharide) plus a placebo (Mediterranean-type diet (prebiotic group, n = 19) vs a placebo supplement (2.8 g xylose) plus a diet low in FODMAP (low-FODMAP group, n = 21) for 4 weeks; patients were then followed for 2 weeks. The primary outcome was effects on composition of the fecal microbiota, analyzed by 16S sequencing. Secondary outcomes were intestinal gas production and digestive sensations. After 4 weeks, we observed opposite effects on microbiota in each group, particularly in relation to the abundance of Bifidobacterium sequences (increase in the prebiotic group and decrease in the low-FODMAP group; P = .042), and Bilophila wadsworthia (decrease in the prebiotic group and increase in the low-FODMAP group; P = .050). After 4 weeks, both groups had statistically significant reductions in all symptom scores, except reductions in flatulence and borborygmi were not significant in the prebiotic group. Although the decrease in symptoms persisted for 2 weeks after patients discontinued prebiotic supplementation, symptoms reappeared immediately after patients discontinued the low-FODMAP diet. Intermittent prebiotic administration might therefore be an alternative to dietary restrictions for patients with functional gut symptoms. ClinicalTrials.gov no.: NCT02210572.

Effect of prucalopride on intestinal gas tolerance in patients with functional bowel disorders and constipation.

BACKGROUND AND AIM: Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. The aim of this study is to determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation. METHODS: Twenty-four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross-over design. On each study day, an intestinal gas challenge test was performed. During the five previous days, prucalopride (2 mg/day) or placebo was administered. Abdominal symptoms, stool frequency, and stool consistency were recorded during the treatment period on daily questionnaires. RESULTS: During the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had significant gas retention (≥ 200 mL) while on placebo. However, in those patients who had increased symptoms during the gas test (≥ 3 on a 0 to 6 scale) when on placebo, prucalopride did significantly reduce the perception of symptoms (2.3 ± 0.5 mean score vs 3.5 ± 0.3 on placebo; P = 0.045). During the treatment period with prucalopride, patients exhibited an increase in the total number of bowel movements and decreased stool consistency compared with placebo. CONCLUSION: Prucalopride reduces abdominal symptoms without modifying gas retention when patients with functional bowel disorders are challenged with the gas transit and tolerance test. European Clinical Trials Database (EudraCT2011-006354-86).

Small Bowel Motility.

PURPOSE OF REVIEW: Small bowel motility disorders constitute a relatively small but important segment of clinical gastroenterology. Presenting features encompass a broad range of symptom manifestations and severity: from chronic functional-type complaints to life-threatening nutritional impairment. Diagnostic assessment of patients with suspected intestinal motility disorders is often hampered by the complexity of measuring intestinal contractile activity in humans. In this review, we describe and critically comment the main current and forthcoming methodologies. RECENT FINDINGS: Beyond conventional small bowel manometry, radiological methods, and intestinal transit tests that have been available for several decades, now we focus on novel methodologies such as high-resolution manometry, magnetic resonance methodology, and endoluminal capsule image analysis. Gradual introduction of new approaches to diagnostic investigation of patients with suspected intestinal motility disorders should facilitate a less invasive and more accurate characterization of disturbed motor function. Enhanced understanding of the pathophysiological basis of clinical conditions should allow better application of therapeutic approaches that are also highlighted in this review.

Diabetic neuropathy in the gut: pathogenesis and diagnosis.

The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive function so that digestion is normally not perceived. However, under certain circumstances, digestive stimuli may activate sensory afferents and give rise to conscious sensations. Both reflex and sensory signals are modulated by a balance of excitatory and inhibitory mechanisms. Patients with diabetes may develop a neuropathy affecting the control of gastric and/or intestinal motor function and the sensory innervation as well. During fasting the stomach is contracted and relaxes to accommodate a meal. After ingestion the stomach progressively recontracts and this contraction gently produces gastric emptying. Impairment of excitatory pathways affects the contraction of the stomach, which may result in delayed gastric emptying and vomiting of retained food. Conversely, alteration of the inhibitory neural pathways results in impaired relaxation of the stomach in response to a meal; in this case increased wall tension may produce early satiation, fullness and nausea. Diabetic neuropathy may distort the control of intestinal motility, which can lead to diverse symptoms such as diarrhoea, constipation, intestinal distension and abdominal pain. Neuropathy in diabetes may also affect the sensory nerves of the gut, and depending on which pathways are involved, perception may be increased or reduced. In summary, in patients with diabetic neuropathy, disorders of gut motor function are associated with sensory abnormalities, and the combination of impaired pathways determines the clinical consequences. This review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Hans Törnblom, DOI: 10.1007/s00125-015-3829-9 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ).

Classification of functional bowel disorders by objective physiological criteria based on endoluminal image analysis.

We have previously developed an original method to evaluate small bowel motor function based on computer vision analysis of endoluminal images obtained by capsule endoscopy. Our aim was to demonstrate intestinal motor abnormalities in patients with functional bowel disorders by endoluminal vision analysis. Patients with functional bowel disorders (n = 205) and healthy subjects (n = 136) ingested the endoscopic capsule (Pillcam-SB2, Given-Imaging) after overnight fast and 45 min after gastric exit of the capsule a liquid meal (300 ml, 1 kcal/ml) was administered. Endoluminal image analysis was performed by computer vision and machine learning techniques to define the normal range and to identify clusters of abnormal function. After training the algorithm, we used 196 patients and 48 healthy subjects, completely naive, as test set. In the test set, 51 patients (26%) were detected outside the normal range (P < 0.001 vs. 3 healthy subjects) and clustered into hypo- and hyperdynamic subgroups compared with healthy subjects. Patients with hypodynamic behavior (n = 38) exhibited less luminal closure sequences (41 ± 2% of the recording time vs. 61 ± 2%; P < 0.001) and more static sequences (38 ± 3 vs. 20 ± 2%; P < 0.001); in contrast, patients with hyperdynamic behavior (n = 13) had an increased proportion of luminal closure sequences (73 ± 4 vs. 61 ± 2%; P = 0.029) and more high-motion sequences (3 ± 1 vs. 0.5 ± 0.1%; P < 0.001). Applying an original methodology, we have developed a novel classification of functional gut disorders based on objective, physiological criteria of small bowel function.

Biofeedback-guided control of abdominothoracic muscular activity reduces regurgitation episodes in patients with rumination.

BACKGROUND & AIMS: Rumination syndrome is characterized by effortless recurrent regurgitation of recently ingested food into the mouth, with consequent expulsion or re-chewing and swallowing. We investigated whether rumination is under volitional control and can be reversed by behavioral treatment. METHODS: We performed a prospective study of 28 patients who fulfilled the Rome criteria for rumination and had no organic disorders on the basis of a thorough evaluation. The diagnosis of rumination was confirmed by intestinal manometry (abdominal compression associated with regurgitation). Patients were trained to modulate abdominothoracic muscle activity under visual control of electromyographic recordings. Recordings were made after challenge meals, before training (baseline), and during 3 treatment sessions. Outcome was measured by questionnaires administered daily for 10 days before training, immediately after training, and at 1, 3, and 6 months after training. RESULTS: By the end of the 3 sessions, patients had effectively learned to reduce intercostal activity (by 50% ± 2%; P < .001 vs basal) and anterior wall muscle activity (by 30% ± 6%; P < .001 vs basal). Patients reported 27 ± 1 regurgitation episodes/day at baseline and 8 ± 2 episodes/day immediately after treatment. Regurgitation episodes decreased further to 4 ± 1 episodes at 6 months after training. CONCLUSIONS: Rumination is produced by an unperceived somatic response to food ingestion that disrupts abdominal accommodation and can be effectively corrected by biofeedback-guided control of abdominothoracic muscular activity.

New insights into the characterization of the mechanism of action of hyoscine butylbromide in the human colon ex vivo.

INTRODUCTION: Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. METHODS: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. RESULTS: In the presence of tetrodotoxin (TTX), HBB and atropine 1 µM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. CONCLUSIONS: This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.

Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study.

Introduction: Drotaverine, paracetamol, and peppermint oil are often prescribed for the treatment of gastrointestinal spasm and pain. This study aimed to evaluate the effect of these drugs alone and combined with the well-known antispasmodic hyoscine butylbromide on the human colon. Methods: Colon samples were obtained from macroscopically normal regions of 68 patients undergoing surgery and studied in muscle bath. Drotaverine, paracetamol, and peppermint oil were tested alone and in combination with hyoscine butylbromide on (1) spontaneous contractility induced by isometric stretch (in the presence of 1 µM tetrodotoxin) and (2) contractility induced by 10-5 M carbachol and after (3) electrical field stimulation-induced selective stimulation of excitatory (in the presence of 1 mM Nω-nitro-L-arginine and 10 µM MRS2179) and (4) inhibitory (under non-adrenergic, non-cholinergic conditions) pathways. (5) Drotaverine alone was also tested on cAMP-dependent pathway activated by forskolin. Results: Compared with the vehicle, drotaverine and paracetamol (10-9-10-5 M) did not modify spontaneous contractions, carbachol-induced contractions, and responses attributed to selective activation of excitatory pathways. The addition of hyoscine butylbromide (10-7-10-5 M), concentration-dependently reduced myogenic contractions and carbachol- and electrical field stimulation-induced contractile responses. The association of paracetamol (10-4 M) and hyoscine butylbromide (10-7-10-5 M) was not different from hyoscine butylbromide alone (10-7-10-5 M). At higher concentrations (10-3M-3*10-3 M), paracetamol decreased myogenic and carbachol-induced contractions. The adenylate cyclase activator, forskolin, concentration-dependently reduced contractility, leading to smooth muscle relaxation. The effect of forskolin 10-7 M was concentration-dependently enhanced by drotaverine (10-6M-10-5M). Discussion: Peppermint oil reduced myogenic activity and carbachol- and electrical field stimulation-induced contractions. The association of hyoscine butylbromide and peppermint oil was synergistic since the interaction index measured with the isobologram was lower than 1. No effect was seen on the neural-mediated inhibitory responses with any of the drugs studied although peppermint oil reduced the subsequent off-contraction. Drotaverine and hyoscine butylbromide have a complementary effect on human colon motility as one stimulates the cAMP inhibitory pathway and the other inhibits the excitatory pathway. Peppermint oil is synergic with hyoscine butylbromide suggesting that a combination therapy may be more effective in treating patients. In contrast, at therapeutic concentrations, paracetamol does not modify colonic contractility, suggesting that the association of paracetamol and hyoscine butylbromide has independent analgesic and antispasmodic properties.

End to End Colonic Content Assessment: ColonMetry Application.

The analysis of colonic contents is a valuable tool for the gastroenterologist and has multiple applications in clinical routine. When considering magnetic resonance imaging (MRI) modalities, T2 weighted images are capable of segmenting the colonic lumen, whereas fecal and gas contents can only be distinguished in T1 weighted images. In this paper, we present an end-to-end quasi-automatic framework that comprises all the steps needed to accurately segment the colon in T2 and T1 images and to extract colonic content and morphology data to provide the quantification of colonic content and morphology data. As a consequence, physicians have gained new insights into the effects of diets and the mechanisms of abdominal distension.

Anatomical landmarks localization for capsule endoscopy studies.

Wireless Capsule Endoscopy is a medical procedure that uses a small, wireless camera to capture images of the inside of the digestive tract. The identification of the entrance and exit of the small bowel and of the large intestine is one of the first tasks that need to be accomplished to read a video. This paper addresses the design of a clinical decision support tool to detect these anatomical landmarks. We have developed a system based on deep learning that combines images, timestamps, and motion data to achieve state-of-the-art results. Our method does not only classify the images as being inside or outside the studied organs, but it is also able to identify the entrance and exit frames. The experiments performed with three different datasets (one public and two private) show that our system is able to approximate the landmarks while achieving high accuracy on the classification problem (inside/outside of the organ). When comparing the entrance and exit of the studied organs, the distance between predicted and real landmarks is reduced from 1.5 to 10 times with respect to previous state-of-the-art methods.

Clinical significance of small bowel manometry patterns suggestive of intestinal obstruction.

INTRODUCTION: Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. METHODS: Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. RESULTS: The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. CONCLUSION AND INFERENCE: Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry.

Distinctive gastrointestinal motor dysfunction in patients with MNGIE.

BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare mitochondrial disease caused by mutations in TYMP, encoding thymidine phosphorylase. Clinically it is characterized by severe gastrointestinal dysmotility associated with cachexia and a demyelinating sensorimotor polyneuropathy. Even though digestive manifestations are progressive and invariably lead to death, the features of gastrointestinal motor dysfunction have not been systematically evaluated. The objective of this study was to describe gastrointestinal motor dysfunction in MNGIE using state-of-the art techniques and to evaluate the relationship between motor abnormalities and symptoms. METHODS: Prospective study evaluating gastrointestinal motor function and digestive symptoms in all patients with MNGIE attended at a national referral center in Spain between January 2018 and July 2022. KEY RESULTS: In this period, five patients diagnosed of MNGIE (age range 16-46 years, four men) were evaluated. Esophageal motility by high-resolution manometry was abnormal in four patients (two hypoperistalsis, two aperistalsis). Gastric emptying by scintigraphy was mildly delayed in four and indicative of gastroparesis in one. In all patients, small bowel high-resolution manometry exhibited a common, distinctive dysmotility pattern, characterized by repetitive bursts of spasmodic contractions, without traces of normal fasting and postprandial motility patterns. Interestingly, objective motor dysfunctions were detected in the absence of severe digestive symptoms. CONCLUSIONS AND INFERENCES: MNGIE patients exhibit a characteristic motor dysfunction, particularly of the small bowel, even in patients with mild digestive symptoms and in the absence of morphological signs of intestinal failure. Since symptoms are not predictive of objective findings, early investigation is indicated.

Effect of colonic distension on small bowel motility measured by jejunal high-resolution manometry.

BACKGROUND: Abnormal motility patterns in the jejunum can be detected in patients with prominent colonic content, and these abnormalities may be due to either a primary jejunal dysfunction or a reflex distortion. The objective of the present study was to determine the effect of colonic distension on small bowel postprandial motility using high-resolution manometry. METHODS: Single center, controlled, parallel, randomized, single blind study in healthy subjects testing the effect of colonic filling vs sham infusion on the responses to a meal in 16 healthy subjects. Nutrients were continuously infused in the proximal jejunum (2 Kcal/min) during the 2-h study period to induce a steady-state postprandial motor pattern. Jejunal motility was measured by water-perfused, high-resolution manometry. After 1 h postprandial recording (basal period), gas was infused during 7.5 min via a rectal tube (720 mL or sham infusion), and jejunal motility was recorded for another hour. KEY RESULTS: Jejunal postprandial motility during the basal period was characterized by two overlapping components: a) continuous segmental activity (non-propagated or shortly propagated) and b) intercurrent propagated fronts (3.8 ± 1.1 fronts of 2-5 clustered contractions/h >10 cm propagation). As compared to sham infusion, colonic gas filling: a) inhibited continuous segmental contractile activity (by 17 ± 4%; p = 0.044 vs control group) and b) stimulated intermittent propagated fronts (up to 9.0 ± 2.2 fronts/h; p = 0.017 vs control group). CONCLUSIONS AND INFERENCES: Long retrograde reflexes induced by colonic distension distort the balance between segmental and propagated activity, and may affect the normal response of the jejunum to food ingestion. Jejunal manometry in patients may be artifacted by colonic overload.