Beatrice Salvioli

New pathophysiological mechanisms in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional, multifactorial disease characterized by abdominal pain and erratic bowel habit. Changes in gastrointestinal motor function, enhanced perception of stimuli arising from the gut wall and psychosocial factors are thought to be major contributors for symptom generation. In recent years, several additional factors have been identified and postulated to interact with these classical mechanisms. Reduced ability to expel intestinal gas with consequent gas trapping and bowel distension may contribute to abdominal discomfort/pain and bloating. Abnormal activation of certain brain regions following painful stimulation of the rectum suggests altered processing of afferent signals. An acute gastrointestinal infection is now a recognized aetiological factor for symptom development in a subset of IBS patients (i.e. post‐infectious IBS), who are probably unable to down‐regulate the initial inflammatory stimulus efficiently. Furthermore, low‐grade inflammatory infiltration and activation of mast cells in proximity to nerves in the colonic mucosa may also participate in the frequency and severity of perceived abdominal pain in post‐infectious and non‐specific IBS. Initial evidence suggests the existence of changes in gut microflora, serotonin metabolism and a genetic contribution in IBS pathophysiology. These novel mechanisms may aid a better understanding of the complex pathophysiology of IBS and to develop new therapies.

Chronic intestinal pseudo-obstruction: manifestations, natural history and management

Abstract  Chronic intestinal pseudo‐obstruction (CIPO) is a rare pathological condition characterized by a marked derangement of gut propulsive motility mimicking mechanical obstruction, in the absence of any lesion occluding the gut lumen. This disease is often associated with a disabling and potentially life‐threatening complications and is still too often unrecognized even in referral centres. As a result, patients receive neither appropriate care nor recognition of their severe health condition. Medical and surgical therapies are often unsatisfactory and long‐term outcome turns out to be poor in the vast majority of cases. This article focuses on the main clinical features, the management and long‐term outcome of patients affected by CIPO, with particular emphasis on those aspects which remain a matter of debate.

Predominant symptoms identify different subgroups in functional dyspepsia.

OBJECTIVE:Dyspepsia is a common syndrome that often defies diagnosis. Whether the unexplained (or “functional”) dyspepsia represents a homogeneous syndrome or includes different subgroups with specific clinical features has not been clarified. The aim of this study was to investigate the relationship between symptom severity, demographic features, and gastric dysmotility in a large series of patients with functional dyspepsia.METHODS:Severity of individual digestive symptoms, demographic features, and scintigraphic gastric emptying of solids were evaluated in 483 patients with chronic unexplained dyspepsia.RESULTS:Two main subgroups were identified. The first was characterized by predominant epigastric pain, male gender (61%), and normal gastric emptying. The second subgroup was characterized by predominant nonpainful symptoms, female gender (60%), a high frequency of associated irritable bowel syndrome (30%), and delayed gastric emptying (42%). A third group included approximately one-third of patients who did not present with any predominant symptom, and was characterized by a high frequency of delayed gastric emptying (30%), overlapping irritable bowel syndrome (28%), and gastroesophageal reflux disease (41%).CONCLUSIONS:Different subgroups exist among patients with functional dyspepsia seen in a referral center. They can be identified by the predominant symptom and are characterized by different demographic, clinical, and pathophysiological features.

Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases

Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis.

Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia.

Abstract OBJECTIVE: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean ± SE) of nitrinergic neurons per section was visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 ± 0.1) and the gastric component (2 ± 0.6) of the LES as compared to those in controls (15 ± 5 and 12 ± 4, respectively; p CONCLUSIONS: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion

OBJECTIVE:In healthy individuals, intraluminal lipids delay intestinal gas clearance, and this reflex is exaggerated in patients with irritable bowel syndrome (IBS). Our aim was to determine the site of action of abnormal lipid-induced reflexes in IBS.METHODS:In six patients with (IBS) predominantly complaining of bloating and in six healthy subjects, a mixture of gas (N2, O2, and CO2 in venous proportions to minimize diffusion) was infused (12 mL/min) either into the jejunum or into the ileum for 2 h, with simultaneous perfusion of lipids (0.5 kcal/min) into the proximal duodenum. Rectal gas evacuation was measured by a barostat. Abdominal perception (by a 0–6 scale) and girth changes were measured at 15-min intervals. The effects of jejunal versus ileal gas infusion were compared by paired tests in random order on separate days.RESULTS:IBS patients exhibited significant gas retention during infusion of gas into the jejunum (398 ± 90 mL vs −210 ± 105 mL in health, p < 0.05) but not during ileal infusion (−79 ± 87 mL vs −79 ± 78 mL in health, NS; p < 0.05 vs jejunal infusion). Gas retention during jejunal gas infusion in IBS patients was associated with significant abdominal distension (11 ± 3 mm girth increment vs 0 ± 1 mm during ileal gas infusion and 1 ± 1 mm in health, p < 0.05 for both) and abdominal symptoms (3.6 ± 0.6 score vs 2.6 ± 0.7 score during ileal gas infusion and 1.6 ± 0.5 score in health, p < 0.05 for both).CONCLUSIONS:In IBS patients intraluminal lipids impair intestinal gas clearance because of upregulated reflex inhibition of small bowel transit, without appreciable colonic effects.

Rectal function and bowel habit in irritable bowel syndrome.

OBJECTIVES:Rectal compliance may influence rectal perception, but their functional implications remain incompletely understood. Our aim was to determine whether rectal function is related to bowel habit in the irritable bowel syndrome.METHODS:The responses to fixed tension rectal distension applied by means of a tensostat were compared among constipation-predominant (n = 9), diarrhea-predominant (n = 7), alternating habit (n = 11) irritable syndrome subgroups, and healthy controls (n = 15).RESULTS:Overall, patients had normal rectal compliance and increased perception, but compliance was lower in diarrhea-predominant as compared to constipation-predominant patients (6.7 ± 0.7 ml/mmHg vs. 9.9 ± 0.7 ml/mmHg, respectively; p < 0.05) and perception was higher (39 ± 6 g vs. 64 ± 9 g tolerance, respectively; p < 0.05).CONCLUSION:Distinctive tensosensitivity and compliance characterize rectal function in irritable bowel syndrome subgroups with different bowel habit.

Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.

Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric ganglionitis), along with severe intestinal motor abnormalities, may accompany paraneoplastic syndromes, neurological disorders and gastrointestinal infections, although rare cases can be idiopathic. In this report, we describe the case of a patient who presented with chronic intractable vomiting and weight loss associated with idiopathic myenteric ganglionitis mainly involving the stomach. Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of substance P/tachykinin immunoreactive staining in nerve fibres and myenteric neurones. Following systemic steroid therapy, the patients symptoms dramatically improved, and after one year of follow-up his general condition remains satisfactory. The possible mechanisms leading to symptom generation and gastric dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

Autonomic nervous system dysregulation in irritable bowel syndrome

Autonomic nervous system (ANS) regulation may be altered in functional diseases, including irritable bowel syndrome (IBS), but published data are not clear to date. The aim of the study was to analyze ANS function in IBS subjects classified by Rome III criteria and healthy controls using standardized technique.

Gastric Emptying and Dyspeptic Symptoms in Patients with Nonautoimmune Fundic Atrophic Gastritis

Our aim was to evaluate the relationship between gastric emptying and demographic, clinical, histological, and secretory features in patients with nonautoimmune fundic atrophic gastritis. Only 31% of 45 patients with fundic atrophic gastritis presented with achlorhydria. Scintigraphic gastric emptying of solids was delayed compared to healthy controls. Patients with achlorhydria showed gastric emptying rates lower than those with preserved acid secretion. Significant, but weak, correlations were observed between emptying rates and both peak acid output (Rs = 0.33) and serum gastrin levels (Rs = −0.36), but not with grading of mucosal atrophy. No symptom differences were observed between patients with or without achlorhydria, but a weak correlation was detected between peak acid output and the severity of epigastric pain (Rs = 0.40). In conclusion, patients with fundic atrophic gastritis present delayed gastric emptying that is weakly related to the reduction of the acid secretion and the raising of serum gastrin levels rather than to the severity of the atrophy.