Functional Neuroimaging in Irritable Bowel Syndrome: A Systematic Review Highlights Common Brain Alterations With Functional Movement Disorders.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurring abdominal pain and altered bowel habits without detectable organic causes. This study aims to provide a comprehensive overview of the literature on functional neuroimaging in IBS and to highlight brain alterations similarities with other functional disorders - functional movement disorders in particular. We conducted the bibliographic search via PubMed in August 2020 and included 50 studies following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. Overall, our findings showed an aberrant activation and functional connectivity of the insular, cingulate, sensorimotor and frontal cortices, the amygdala and the hippocampus, suggesting an altered activity of the homeostatic and salience network and of the autonomous nervous system. Moreover, glutamatergic dysfunction in the anterior insula and hypothalamic pituitary axis dysregulation were often reported. These alterations seem to be very similar to those observed in patients with functional movement disorders. Hence, we speculate that different functional disturbances might share a common pathophysiology and we discussed our findings in the light of a Bayesian model framework.

Carcinoid Syndrome and Hyperinsulinemic Hypoglycemia Associated with Neuroendocrine Neoplasms: A Critical Review on Clinical and Pharmacological Management.

The carcinoid syndrome (CS) and hyperinsulinemic hypoglycemia (HH) represent two of the most common clinical syndromes associated with neuroendocrine neoplasms (NENs). The former is mainly related to the serotonin secretion by a small bowel NEN, whereas the latter depends on an insulin hypersecretion by a pancreatic insulinoma. Both syndromes/conditions can affect prognosis and quality of life of patients with NENs. They are often diagnosed late when patients become strongly symptomatic. Therefore, their early detection and management are a critical step in the clinical management of NEN patients. A dedicated and experienced multidisciplinary team with appropriate therapeutic strategies is needed and should be encouraged to optimize clinical outcomes. This review aims to critically analyze clinical features, evidence and treatment options of CS and HH and therefore to improve their management.

Primary sclerosing cholangitis associated with inflammatory bowel disease: an update.

Primary sclerosing cholangitis (PSC) is a chronic progressive disease, usually associated with underlying inflammatory bowel diseases (IBDs), with a prevalence of 60-80% in western countries. Herein, we review the current knowledge about the association between PSC and IBD in terms of clinical approach and long-term patient management. A PubMed search was conducted for English-language publications from 2000 through 2015 using the following keywords: primary sclerosing cholangitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, diagnosis, therapy, follow-up, and epidemiology. In terms of diagnosis, liver function tests and histology are currently used. The medical treatment options for PSC associated with IBD do not differ from the cases of PSC alone, and include ursodeoxycholic acid and immunosuppressive agents. These treatments do not seem to improve survival, even if ursodeoxycholic acid given at low doses may be chemopreventive against colorectal cancer (CRC). Liver transplantation is the only potential curative therapy for PSC with reported survival rates of 85 and 70% at 5 and 10 years after transplant; however, there is a risk for PSC recurrence, worsening of IBD activity, and de-novo IBD occurrence after liver transplantation. PSC-IBD represents an important public health concern, especially in view of the increased risk for malignancy, including CRC. Long-life annual surveillance colonoscopy is usually recommended, although the exact timescale is still unclear. Further studies are required both to clarify whether annual colonoscopy is cost-effective, especially in younger patients, and to identify potential pharmaceutical agents and genetic targets that may retard disease progression and protect against CRC.

The role of dietary supplements in inflammatory bowel disease: a systematic review.

Inflammatory bowel diseases (IBD) are chronic immune disorders of unclear aetiology. Dietary deficiencies may be a potential pathogenic factor in their development. Patients often take food supplements without knowledge of any evidence base. We have therefore assessed the evidence for food supplementation in the management of IBD. A PubMed search was performed for the terms Inflammatory bowel disease; nutritional deficiencies; dietary supplements; curcumin; green tea; vitamin D/other vitamins; folic acid; iron; zinc; probiotics; andrographis paniculata; and boswellia serrate. PubMed was used to search for all relevant articles published between January 1975 and September 2015. Curcumin supplementation has been reported to be effective in reducing the symptoms and the inflammatory indices in IBD patients. Similar results have been observed for green tea; however, pertinent studies are limited. Vitamin D supplementation may help to increase bone mineral density in IBD patients and to reduce disease activity. IBD patients with ileal resections higher than 20 cm may develop vitamin B12 deficiency that requires parenteral supplementation. There is no current evidence to support fat-soluble vitamin supplementation in IBD patients. Zinc and iron should be supplemented in selected cases. Probiotics (VSL#3) may reduce disease activity in IBD patients with pouchitis. Complementary and alternative medicines are used by IBD patients and some studies have shown promising results. In summary, attention to dietary factors such as curcumin, green tea and vitamins, including vitamins D and B12, appears to be beneficial and, if necessary, supplementation may be appropriate.

Elevated liver enzymes in inflammatory bowel disease: the role and safety of infliximab.

BACKGROUND: Abnormal liver enzymes are frequently encountered in inflammatory bowel disease (IBD) patients. Infliximab has been implicated in inducing drug-induced liver injury, autoimmune hepatitis or reactivation of hepatitis B virus. We aimed to clarify the role of infliximab in liver impairment in an IBD cohort. STUDY: A total of 305 patients with IBD, without evidence of chronic liver disease, were included in the study and retrospectively evaluated. Laboratory and clinical data were retrieved from a prospectively acquired database. In all, 176 consecutive patients treated with infliximab during the last 5 years were compared with a matched population of 129 patients who did not receive any antitumour necrosis factor treatment. RESULTS: Elevation of alanine transaminase (ALT) was frequent in the entire population (36.4%) and it was not significantly associated with the use of infliximab (P=0.284). Elevations more than 3 upper limit of normal were observed in 7.9% and these resolved spontaneously in 83%. The use of immunomodulators was the only factor that was significantly associated with liver enzyme abnormalities in multivariate analysis [odds ratio (OR) 2.666, 95% confidence interval (CI) 1.576-4.511, P<0.005]. Overall, 39% of patients on infliximab had elevated liver enzymes and this was associated with increased ALT before starting infliximab (OR 3.854, 95% CI 1.800-8.251, P=0.001) and with longer duration of infliximab treatment (OR 1.030, 95% CI 1.013-1.047, P=0.001). CONCLUSION: Elevated liver enzymes are frequently found in IBD patients and they usually resolve spontaneously. The use of immunomodulators was independently associated with increased ALT. Infliximab is relatively safe in terms of liver impairment and discontinuation of treatment is rarely required in the setting of modest elevations of ALT.

The impact of diet and nutrition in the prevention and progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. There is growing evidence for a chemopreventive role of nutrition in the development of HCC in at risk populations. Bibliographical searches were performed in PubMed for the terms 'nutrition and hepatocellular carcinoma', 'nutrition and liver cancer', 'nutrition and hepatic cancer', 'diet and hepatocellular carcinoma', 'diet and liver cancer'. High dietary sugar intake should be discouraged in at risk populations. Coffee, polyphenols, vanadium, dietary fibre, fruits and vegetables show encouraging results in terms of chemoprevention. Red meat intake may be associated with increased risk of HCC. The evidence for fatty acids is inconclusive, but they might exert anti-cancer effects. Inconclusive results are available on vitamins, selenium probiotics and prebiotics. There is increasing evidence that diet may play an important role in the development of HCC, and may also have a chemopreventive role in at risk populations.

An esophageal gastrointestinal stromal tumor in a patient with MEN1-related pancreatic gastrinoma: an unusual association and review of the literature.

Both multiple endocrine neoplasia type 1 (MEN1)-related gastrinomas and gastrointestinal stromal tumors (GISTs) are rare neoplasms, and their association has been rarely reported. We describe an unusual association between a GIST and a MEN1-related gastrinoma. A 44-year-old man had undergone surgical removal of a pancreatic gastrinoma in 2004 and was then administered long-term somatostatin analogs, and diagnosed as having MEN1 syndrome. Following an uneventful follow-up, in April 2009, an upper gastrointestinal tract endoscopy showed esophageal narrowing, with evidence of a 2-cm solid mass on endoscopic ultrasonography. Histology revealed a tumor composed of elongated cells with plump cytoplasm arranged in a storiform pattern. The immunophenotype of the lesion was CD117 and Platelet Derived Growth Factor (PDGF) positive, whereas alpha-1 muscle actin and S-100 protein were negative. Due to morphological and immunohistochemical results, a final diagnosis of esophageal GIST was made. The association between GISTs and MEN1 could be casual, although a single case of the coexistence of a GIST and a MEN1-related gastrinoma has already been reported. A role of the MEN1 gene in the pathogenesis of GISTs could be hypothesized.