Multimodal Surgical Approach for Adult Patients With Chronic Intestinal Pseudo-Obstruction: Clinical and Psychosocial Long-term Outcomes.

BACKGROUND: Clinical and psychosocial outcomes of a multimodal surgical approach for chronic intestinal pseudo-obstruction were analyzed in 24 patients who were followed over a 2- to 12-year period in a single center after surgery or intestinal/multivisceral transplant (CTx). METHODS: The main reasons for surgery were sub-occlusion in surgery and parenteral nutrition-related irreversible complications with chronic intestinal failure in CTx. RESULTS: At the end of follow-up (February 2015), 45.5% of CTx patients were alive: after transplantation, improvement in intestinal function was observed including a tendency toward recovery of oral diet (81.8%) with reduced parenteral nutrition support (36.4%) in the face of significant mortality rates and financial costs (mean, 202.000 euros), frequent hospitalization (mean, 8.8/re-admissions/patient), as well as limited effects on pain or physical wellness. CONCLUSIONS: Through psychological tests, transplant recipients perceived a significant improvement of mental health and emotional state, showing that emotional factors were more affected than were functional/cognitive impairment and social interaction.

Comparison between small bowel manometric patterns and full-thickness biopsy histopathology in severe intestinal dysmotility.

BACKGROUND: Intestinal manometry is the current standard for direct evaluation of small bowel dysmotility. Patients with abnormal motility can either be diagnosed of pseudo-obstruction when there are radiological findings mimicking mechanical intestinal obstruction or of enteric dysmotility when these findings are absent. The aim of the present study was to prospectively compare small bowel manometric abnormalities with histopathological findings in intestinal full-thickness biopsies in patients with severe dysmotility disorders. METHODS: We investigated 38 patients with intestinal manometry and a subsequent full-thickness intestinal biopsy. Manometric recordings were read by 4 investigators and a diagnostic consensus was obtained in 35 patients. Histopathological analysis, including specific immunohistochemical techniques of small bowel biopsies was performed and compared to manometric readings. KEY RESULTS: Patients with abnormal intestinal manometry had abnormal histopathological findings in 73% of cases. However, manometric patterns did not match with the specific neuromuscular abnormalities. Among patients with a neuropathic manometry pattern and abnormal histopathology, only 23% had an enteric neuropathy, whereas 62% had neuromuscular inflammation, and 15% an enteric myopathy. On the other hand, patients with a myopathic manometry pattern all had abnormal histopathology, however, none of them with signs of enteric myopathy. CONCLUSION & INFERENCES: Small bowel dysmotility detected by intestinal manometry is often associated with abnormal neuromuscular findings in full-thickness biopsies. However, there is no correlation between the specific manometric patterns and the histopathological findings.

Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.

BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS: We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS: A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS: The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.

Patient-reported outcomes and gut dysmotility in functional gastrointestinal disorders.

BACKGROUND: Unlike chronic idiopathic intestinal pseudo-obstruction (CIIP), severe digestive syndromes that are not characterized by episodes resembling mechanical obstruction remain poorly characterized. The present study compared clinical features, small bowel motility, and quality of life (QoL) in patients with CIIP or severe functional gastrointestinal disorders (SFGID), compared to irritable bowel syndrome (IBS). METHODS: We enrolled 215 consecutive patients: 70 CIIP, 110 malnourished SFGID [body mass index (BMI) 17.8±1.8kg m(-2) ] and 35 non-malnourished SFGID (BMI 22.8±3.6kgm(-2) ). KEY RESULTS: Abnormal motor patterns that fulfilled diagnostic criteria for small bowel dysmotility were virtually absent in IBS patients, but were recorded in69 CIIP patients (98.6%), 82 malnourished SFGID patients (74.5%;), and 23 SFGID patients without malnutrition (65.7%) (P<0.0001). CIIP patients presented more frequently abnormal activity fronts, lack of response to feeding, and hypomotility than malnourished and non-malnourished SFGID patients (61.4%vs 42.7% and 31.4%, P<0.05 only vs non-malnourished SFGID; 8.6%vs 0.9% and 2.9%; 21.4%vs 0.9% and 0%, P<0.05). Quality of life mean scores were all significantly lower in CIIP patients and malnourished SFGID patients than in IBS. Bodily pain, general health, and vitality scores were lower in CIIP also compared to non-malnourished SFGID. CONCLUSIONS & INFERENCES: Chronic idiopathic intestinal pseudo-obstruction and SFGIDs are frequently associated with small bowel dysmotility and marked derangements of QoL which are significantly more severe than in IBS and result particularly in being severe in patients with recurrent sub occlusive episodes or inability to maintain a normal body weight.

Chronic intestinal pseudo-obstruction related to viral infections.

Chronic intestinal pseudo-obstruction (CIPO), one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Analysis of full-thickness biopsy samples may unravel structural changes of the neuromuscular layer involving the whole gut, although the midgut is usually worst affected. Intestinal pseudo-obstruction can occur in association with systemic neurological, endocrine, and connective tissue diseases or malignancy but, when no recognizable etiology is found, CIPO is referred to as idiopathic (CIIPO). The latter form can be diagnosed early in life due to a genetic etiology or in adulthood when a viral origin may be considered. This review addresses the hypothesis that some systemic neurotrophic viral infections can affect the enteric nervous system thereby altering normal peristaltic activity. Available data are reviewed, focusing specifically on herpesviruses or polyomaviruses (JC virus). These suggest that in comparison to a proportion of CIIPO patients, healthy controls rarely harbor viral DNA in the myenteric plexus, leaving open the possibility that a viral infection might have an etiologic role in the development of CIIPO. The review thus provides some new perspectives in the pathophysiology and perhaps targeted treatment of CIIPO.

Natural history of intestinal failure induced by chronic idiopathic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction is a severe, often unrecognized disease characterized by disabling and potentially life-threatening complications over time. The diagnosis is based on the evidence of typical clinical manifestations, radiological evidence of distended bowel loops with air-fluid levels, and the exclusion of any organic obstruction of the gut lumen. The radiological sign of intestinal occlusion allows the distinction from enteric dysmotility, which is characterized by better outcomes. Manometry can play a supportive role in defining the diagnosis, and differences in the manometric pattern of chronic intestinal pseudo-obstruction and enteric dysmotility have been shown. The disease is often unrecognized, and the diagnosis, therefore, delayed by several years. Thus, the majority of patients undergo useless and potentially dangerous surgeries. Long-term outcomes are generally poor despite surgical and medical therapies characterized by disabling and potentially life-threatening complications over time. A substantial percentage of patients requires parenteral nutrition. Failure of this nutritional support represents an indication for small bowel transplantation.

Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study.

BACKGROUND: Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS). AIM: To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study. METHODS: A randomized, double-blind, placebo-controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention-to-treat analysis was performed. RESULTS: Mesalazine markedly reduced immune cells as compared with placebo (P = 0.0082); this effect was ascribed to a marked inhibition of mast cells (P = 0.0014). Mesalazine significantly increased general well-being (P = 0.038), but had no significant effects on abdominal pain (P = 0.084), bloating (P = 0.177) or bowel habits. No serious drug-related adverse events were reported during the study. CONCLUSIONS: Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well-being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS.

JC virus infects the enteric glia of patients with chronic idiopathic intestinal pseudo-obstruction.

BACKGROUND AND AIMS: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterised by severe impairment of intestinal propulsive motility that mimics bowel obstruction. JC virus (JCV) is a polyomavirus that can infect brain glial cells causing a fatal disease, but may also be found throughout the normal gastrointestinal tract. The hypothesis that JCV infects the myenteric plexuses of patients with CIIP was tested. METHODS: 10 patients with CIIP and 61 normal specimens (30 ascending colon and 31 ileum) from patients with uncomplicated colon cancer were studied. DNA was extracted from the myenteric plexuses, and JCV T antigen (TAg) DNA and the viral regulatory region were detected by PCR and sequencing. Immunohistochemistry was performed to detect JCV viral protein expression, neuronal and glial markers. Fluorescence in situ hybridisation was performed for cellular localisation of the JCV infection. RESULTS: Clinical studies demonstrated neurogenic impairment, and pathological analyses showed neuropathy in each patient with CIIP. JCV TAg DNA was found in the myenteric plexuses of 8/10 (80%) of the patients with CIIP and 3/31 (9.7%) of the control patients (p<0.001). All samples were JCV Mad-1 strains. Seven of the 10 CIIP specimens expressed both JCV TAg and the JCV viral protein VP1, while none of the controls expressed either. JCV infection co-localised with glial fibrillary acidic protein expression, a marker of enteric glial cells. CONCLUSION: JCV infection occurs in the myenteric plexuses of patients with CIIP. The JCV localisation in enteroglial cells suggests a possible pathological role for this virus in enteric neuropathy.

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

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.

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 patient's 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.