Pseudo-obstruction syndromes

Chronic intestinal pseudo-obstruction (CIP) is a clinical syndrome characterized by symptoms and signs of intestinal occlusion, in absence of any mechanical obstruction of the gut lumen. It causes impaired transit of intestinal contents and is determined by abnormalities of motor activity. The term CIP is used to indicate a heterogeneous group of disorders with many different pathogenic mechanisms. The defect in the regulation of intestinal transit can be at any level of motility control. Two main types of CIP are recognized, termed respectively myogenic (when smooth muscle cells are affected) and neurogenic (caused by abnormalities of extrinsic and/or intrinsic nervous supplies). Both types may be secondary to a variety of recognizable diseases or idiopathic. In myogenic CIP, intestinal transit is impaired because of lack of propulsive strength; in the neurogenic form, contractions are powerful but not sufficiently co-ordinated to propel intestinal contents aborally in an organized fashion. CIP belongs to the large and loosely defined group of digestive functional disorders. These disorders probably share common pathogenic mechanisms but with different expressiveness. The reasons why only some patients present recurrent symptomatological bouts resembling mechanical occlusion has not been clarified. This aspect is of great clinical relevance and deserves attention, as CIP patients, unlike other patients with severe functional disorders, may undergo repeated, useless and potentially dangerous operations. The diagnosis of CIP may be suggested by clinical features and is based on radiological, endoscopic, manometric, and histological findings. Recent technological improvements facilitate the recognition of this intriguing syndrome. In particular, manometric recording of the small bowel motility, which has long been considered an important research technique, can now also be regarded as a useful diagnostic tool.     

Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?

BACKGROUND & AIMS: Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses. METHODS: The scientific literature since 1966 in all languages cited in Medline was systematically reviewed. RESULTS: Comorbidity with other functional gastrointestinal disorders is high and may be caused by shared pathophysiological mechanisms such as visceral hypersensitivity. Psychiatric disorders, especially major depression, anxiety, and somatoform disorders, occur in up to 94%. The nongastrointestinal nonpsychiatric disorders with the best-documented association are fibromyalgia (median of 49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%). CONCLUSIONS: Multivariate statistical analyses suggest that these are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological. Some models explain the comorbidity of irritable bowel with other disorders by suggesting that each disorder is the manifestation of varying combinations of interacting physiological and psychological factors. An alternative hypothesis is that the irritable bowel diagnosis is applied to a heterogeneous group of patients, some of whom have a predominantly psychological etiology, whereas others have a predominantly biological etiology, and that the presence of multiple comorbid disorders is a marker for psychological influences on etiology.     

Gastrointestinal motility disorders: an update

Gastrointestinal motility disorders encompass a wide array of signs and symptoms that can occur anywhere throughout the luminal gastrointestinal tract. Motility disorders are often chronic in nature and dramatically affect patients' quality of life. These prevalent disorders cause a tremendous impact both to the individual patient and to society as a whole. Significant progress has been made over the last 5 years in understanding the etiology and pathophysiology of gastrointestinal motility disorders. This clinical update will focus on seven of the most common gastrointestinal motility disorders (achalasia, non-achalasia esophageal motility disorders, dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome, and chronic constipation) with an emphasis on current treatment options and new therapeutic modalities.     

Role of Ghrelin in the Pathophysiology of Gastrointestinal Disease

Ghrelin is a 28-amino-acid peptide that plays multiple roles in humans and other mammals. The functions of ghrelin include food intake regulation, gastrointestinal (GI) motility, and acid secretion by the GI tract. Many GI disorders involving infection, inflammation, and malignancy are also correlated with altered ghrelin production and secretion. Although suppressed ghrelin responses have already been observed in various GI disorders, such as chronic gastritis, Helicobacter pylori infection, irritable bowel syndrome, functional dyspepsia, and cachexia, elevated ghrelin responses have also been reported in celiac disease and inflammatory bowel disease. Moreover, we recently reported that decreased fasting and postprandial ghrelin levels were observed in female patients with functional dyspepsia compared with healthy subjects. These alterations of ghrelin responses were significantly correlated with meal-related symptoms (bloating and early satiation) in female functional dyspepsia patients. We therefore support the notion that abnormal ghrelin responses may play important roles in various GI disorders. Furthermore, human clinical trials and animal studies involving the administration of ghrelin or its receptor agonists have shown promising improvements in gastroparesis, anorexia, and cancer. This review summarizes the impact of ghrelin, its family of peptides, and its receptors on GI diseases and proposes ghrelin modulation as a potential therapy.     

Dyspepsia and its overlap with irritable bowel syndrome

Patients with functional dyspepsia and the irritable bowel syndrome are commonly seen in both primary care and gastroenterology subspecialty settings. Although functional dyspepsia and the irritable bowel syndrome can occur separately, recent research suggests that they often appear together as an overlap syndrome and thus may represent different portions of a unifying spectrum of disease. Despite their widespread prevalence, the pathogenesis of these disorders is not well established but may include impaired gastric emptying, gastric dysrhythmias, hypersensitivity (to acid exposure and to stretch), and Helicobacter pylori infection. Once other disorders in the differential diagnosis have been excluded, treatment of patients with functional dyspepsia, irritable bowel syndrome, and the overlap syndrome without alarm signs underscores current prevailing pathophysiologies and is generally empiric and symptom based. It is hoped that management of these disorders will become more targeted and efficacious as our understanding of them improves.     

Sobreposición entre los trastornos funcionales de dolor abdominal y enfermedades orgánicas en niños

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.     

Electrical therapies for gastrointestinal motility disorders

Introduction: Gastrointestinal (GI) motility disorders are common in clinical settings, including esophageal motility disorders, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, post-operative ileus, irritable bowel syndrome, diarrhea and constipation. While a number of drugs have been developed for treating GI motility disorders, few are currently available. Emerging electrical stimulation methods may provide new treatment options for these GI motility disorders.

Areas covered: This review gives an overview of electrical therapies that have been, and are being developed for GI motility disorders, including gastroesophageal reflux, functional dyspepsia, gastroparesis, intestinal motility disorders and constipation. Various methods of gastrointestinal electrical stimulation are introduced. A few methods of nerve stimulation have also been described, including spinal cord stimulation and sacral nerve stimulation. Potentials of electrical therapies for obesity are also discussed. PubMed was searched using keywords and their combinations: electrical stimulation, spinal cord stimulation, sacral nerve stimulation, gastrointestinal motility and functional gastrointestinal diseases.

Expert commentary: Electrical stimulation is an area of great interest and has potential for treating GI motility disorders. However, further development in technologies (devices suitable for GI stimulation) and extensive clinical research are needed to advance the field and bring electrical therapies to bedside.     

Trastornos funcionales y motores digestivos

Functional gastrointestinal (GI) disorders are difficult to live with. Many patients would prefer to have an organic disease and a medical report stating the results of a test providing evidence of a lesion. Therefore, further knowledge of the causes and treatment of these disorders is essential. The present article aims to summarize as simply and usefully as possible the most important studies on functional and motor GI disorders presented at the Congress of the American Gastroenterological Association (Digestive Disease Week 2010).The most notable presentations concerned the pathogenic mechanisms and search for new therapies in highly prevalent disorders such as functional dyspepsia, irritable bowel syndrome and constipation but interesting studies were also presented on incontinence, gastroparesis, cyclic vomiting syndrome and achalasia.It is increasingly clear that functional GI disorders are caused by multiple factors and, therefore, that genetic, environment, psychological, microinflammatory and neuroimmune-endocrine factors form part of this complex puzzle. Each year, advances are made in distinct parts of the world, which will hopefully improve patient well-being.     

肠易激综合征重叠症的研究进展

肠易激综合征(IBS)是一种常见的以反复发作的腹痛或腹部不适伴排便频率或粪便性状改变为特征的功能性肠病,可单独发生,亦可与其他疾病并存。IBS除可与胃肠道疾病如胃食管反流病(GERD)、功能性消化不良(FD)、炎症性肠病(IBD)、显微镜肠炎(MC)、乳糜泻等重叠外,还可与非胃肠道疾病如焦虑症、哮喘等重叠。本文从流行病学和病理生理学角度对IBS重叠症作一综述。     

Prokinetic agents for lower gastrointestinal motility disorders

Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudoobstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonie motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation.     

Functional abdominal pain syndrome

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogeneous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.     

What do patients with irritable bowel syndrome dream about? A comparison with inflammatory bowel disease

BACKGROUND: It is a common experience for people to dream of events about which they are either anxious or concerned. We therefore hypothesised that the dreams of patients with irritable bowel syndrome may reflect their worries about their problem especially as hospital out-patients with this disorder tend to exhibit some anxiety. In addition, dreaming about, for instance bowels, in patients with irritable bowel syndrome in excess of that observed in other gastrointestinal disorders may be of importance. AIM: To establish whether patients with irritable bowel syndrome dream about bowel-related issues more than controls or patients with inflammatory bowel disease. PATIENTS AND METHODS: A total of 57 patients with irritable bowel syndrome and 57 patients with inflammatory bowel disease were compared with 60 healthy controls. All subjects completed a structured questionnaire concerning sleeping habits and dream characteristics as well as an assessment of anxiety and depression. RESULTS: There were no differences in the sleeping habits between any of the groups. However, significantly more patients with irritable bowel syndrome and inflammatory bowel disease dreamt about their bowels (22% inflammatory bowel disease patients, 18% irritable bowel syndrome patients vs 3% of controls, p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) and soiling themselves (16% of inflammatory bowel disease patients, 14% of irritable bowel syndrome patients vs 2% of controls; p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) than controls. CONCLUSION: Chronic gastrointestinal disorders, of both a functional and organic nature, may influence the nature of dreams. In those patients who dream about their symptoms, it would be interesting to know whether this affects the course of their disease, either positively or negatively, in any way.     

Placebo responses and placebo effects in functional bowel disorders

The nature and determinants of the placebo response are widely unknown, as are the underlying psychological and biological mechanisms. Placebo response rates in functional bowel disorders (functional dyspepsia, irritable bowel syndrome) trials are similar to those in nonintestinal pain conditions and are comparable with other organic gastrointestinal diseases (duodenal ulcer, inflammatory bowel diseases). In this narrative review, different methodologies (meta-analyses, reanalyses, and experimental setups) are discussed that have been applied to the study of the placebo response in functional dyspepsia and the irritable bowel syndrome.     

Functional gastrointestinal disorders and the potential role of eosinophils

The eosinophil-mast cell-neural pathway may be important in the pathophysiology of functional gastrointestinal disorders characterized by unexplained abdominal pain, disordered defecation, or meal-related discomfort. There is evidence that duodenal eosinophils are increased in functional dyspepsia, whereas mast cells are increased in the lower gut in irritable bowel syndrome, directly supporting a role for a hypersensitivity-type reaction in these disorders. The trigger may be a pathogen, food, or other allergen in the gut mucosa. This trigger may evoke eosinophils, mast cells, and other components to cascade to up-regulate serotonin release, with modulation of the enteric and central nervous systems, creating a vicious cycle. If correct, this theory suggests treatment should specifically target the eosinophil-mast cell pathway.     

Aerophagia and Intestinal Gas

Opinion statement Aerophagia refers to a rather rare disorder that may occur in both children and adults that features repetitive air swallowing and belching and that may result in abdominal distention. There are few, if any, controlled studies to guide therapy, which remains largely supportive but may include behavioral therapy and psychotherapy. Bloating, distention, and other gas-related symptoms are common in functional gastrointestinal disorders, including the irritable bowel syndrome; their pathophysiology remains, for the most part, poorly understood. Two separate phenomena need to be distinguished in these disorders: gas production and gas perception. Thus, whereas gas production, which relates most closely to flatus emissions, is probably within the normal range in most patients with irritable bowel syndrome, gas transport or transit through the gut may be impaired and may lead to the retention of gas within segments of the gut. Visceral hypersensitivity, a common phenomenon in all functional disorders, may exacerbate the sensation of distention and contribute to other “gas-related” symptoms. Few controlled studies have addressed any of these issues. Although, on an empiric basis, dietary therapy may be partially effective in some situations, there is at present no data to support the use of any form of pharmacologic, endoscopic, or surgical therapy for any of these symptoms.     

Altered neuro-endocrine–immune pathways in the irritable bowel syndrome: the top-down and the bottom-up model

The interaction between the brain and the gut as a pathological mechanism of functional gastrointestinal disorders has been recently recognized in the pathophysiology of the irritable bowel syndrome. Communication between central nervous system and enteric nervous system is two-directional: the brain can influence the function of the enteric nervous system and the gut can influence the brain via vagal and sympathetic afferents. In patients with irritable bowel syndrome, symptoms may be caused by alterations either primarily in the central nervous system (top-down model), or in the gut (bottom-up model), or in a combination of both. The brain–gut axis may be stimulated by various stressors either directed to the central nervous system (exteroreceptive stress) or to the gut (interoceptive stress). Particularly, clinical evidence suggest that in complex and multifactorial diseases such as irritable bowel syndrome, psychological disorders represent significant factors in the pathogenesis and course of the syndrome. Neuroimaging techniques have shown functional differences between central process in healthy subjects and patients with irritable bowel syndrome. Moreover, a high prevalence of psychological/psychiatric disorders have been reported in IBS patients compared to controls. Several data also suggest an alteration of neuro-endocrine and autonomic output to the periphery in these patients. This review will examine and discuss the complex interplay of neuro-endocrine–immune pathways, closely associated with neuropsychiatric disorders.     

Irritable bowel syndrome and chronic constipation: Fact and fiction

Irritable bowel syndrome(IBS) and functional constipation(FC) are the most common functional gastrointestinal disorders. According to the Rome ⅢCriteria these two disorders should be theoretically separated mainly by the presence of abdominal pain or discomfort relieved by defecation(typical of IBS) and they should be mutually exclusive. However,many gastroenterologists have serious doubts as regards a clear separation. Both IBS-C and FC,often associated with many other functional digestive and non digestive disorders,are responsible for a low quality of life. The impact of the media on patients' perception of these topics is sometimes disruptive,often suggesting a distorted view of pathophysiology,diagnosis and therapy. These messages frequently overlap with previous subjective opinions and are further processed on the basis of the different culture and the previous experience of the constipated patients,often producing odd,useless or even dangerous behaviors. The aim of this review was to analyze the most common patients' beliefs about IBS-C and CC,helping physicians to understand where they should focus their attention when communicating with patients,detecting false opinions and misconceptions and correcting them on the basis of scientific evidence.     

Advances in our understanding of the pathology of chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIP) represents a particularly difficult clinical challenge. It is a rare and highly morbid syndrome characterised by impaired gastrointestinal propulsion together with symptoms and signs of bowel obstruction in the absence of any lesions occluding the gut lumen. CIP can be classified as either "secondary" to a wide array of recognised pathological conditions or "idiopathic" (CIIP). This review will focus on CIIP, and specifically on the underlying pathological abnormalities. Combined clinical and histopathological studies are needed to highlight new perspectives in the understanding and management of chronic intestinal pseudo-obstruction.     

Trastornos funcionales y motores digestivos

We summarize and discuss the studies presented at the congress of the American Association of Gastroenterology (Digestive Disease Week) that, in our opinion, are of greatest interest. Both clinically and physiopathologically, functional gastrointestinal (GI) disorders are highly complex. A single cause is unlikely to explain symptoms as heterogeneous as those of functional dyspepsia and irritable bowel syndrome (IBS). Therefore, it is easier (and more useful) to try to understand functional GI disorders using a bio-psycho-social model. Moreover, data supporting the combined importance of genetic, organic and psychological factors in the onset and persistence of functional GI disorders are increasingly convincing. This year, new data have been provided on pharmacogenetics in gastroparesis, on microinflammation or alterations in the modulation of somatic and visceral sensitivity in functional dyspepsia, and on the impact of psychological factors in IBS. From the therapeutic point of view, further information has been provided on the role of probiotics, the antinociceptive effect of linaclotide (demonstrated in several studies presented this year), and on the high efficacy of hypnotherapy in patients with IBS. Finally, data on the clinical management of patients with constipation due to pelvic floor dyssynergia and on the safety and efficacy of prucalopride in patients with severe constipation were also of interest.     

Gastroparesis and Gastroparesis-like Syndrome: Response to Therapy and Its Predictors

Purpose The natural history and outcome of patients with gastroparesis is not well known. The aim of this study was to identify the clinical or pathophysiological characteristics, if any, that may be helpful in predicting therapeutic response in this condition. Methods This is a retrospective study of a cohort of patients who presented to a tertiary referral center with symptoms suggestive of gastroparesis. All patients were evaluated by scintigraphic measurement of gastric emptying and symptoms were scored using a modification of the Gastroparesis Cardinal Symptom Index (GCSI). Treatment generally included conservative measures such as antiemetics, prokinetics, tricyclic antidepressants, and analgesics as well as various more invasive interventions in selected patients. Response to treatment was defined as a change in the overall GCSI score of two-thirds or more as compared with baseline. Results Out of a total of 93 patients, 69 patients met the eligibility criteria. Of these, 29 patients had diabetes mellitus and 40 patients had gastroparesis of nondiabetic etiology. Out of 69 patients, 49 were responders (71%) and 20 were nonresponders (29%). The cause (diabetic versus nondiabetic) of gastroparesis or the presence of delayed emptying did not correlate with response. However, the severity of stomach distension, bloating subscale score, and the global GCSI score at baseline presentation were predictive of response by multivariate analysis. Conclusion Higher global GCSI score, bloating subscale score, and severity of stomach distension at baseline presentation correlated with an unfavorable response in gastroparetic patients. On the other hand, neither the etiology of gastroparesis nor associated delay in gastric emptying appeared to be important in the clinical response. Patients with symptoms of typical gastroparesis but without delays in gastric emptying may have a distinct syndrome with a greater proportion of males than classical gastroparesis.