From Regular Catharsis with Castor Oil to Recognizing the Importance of the Intestinal Microbiota.

The need to shed light on the unknown aspects of pathophysiology of common disorders, such as gastrointestinal ones, has led researchers through last decades to study and define the role of microorganisms within the human intestine and their interactions with the host. The progress of technology has permitted the overcoming of culture-based methods to study microbes and paved the way to molecular techniques, which allow the analysis of microbial genome, microbial functions, and metabolism. These progresses opened a window on the world of microbiology and permitted to deepen into the key role played by gut microbiota and dysbiosis in health status and diseases, both gastrointestinal and extraintestinal. So, scientists focused their attention in developing new strategies to restore eubiosis and to manipulate gut microbes by modifying dietary habits, administrating antibiotics, probiotics, and prebiotics and using fecal microbiota transplantation as treatment of gastrointestinal, infectious, cardiovascular, metabolic, immune-mediated, neuro-psychiatric, and oncological disorders. The next challenges will be to elaborate standard protocols with definite outcomes predictors in disease-specific settings.

Guidelines for the management of Helicobacter pylori infection in Italy: The III Working Group Consensus Report 2015.

Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) "open questions" on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

Helicobacter pylori and extragastric diseases.

While Helicobacter pylori infection was initially revealed to be associated only with some gastroduodenal diseases, further studies have shown its possible role in several extragastric diseases. For idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency, the diagnosis of H. pylori infection is recommended, and there are many other conditions such as cardiovascular, neurological, dermatological, and respiratory diseases in which H. pylori may possibly play a role. Interestingly, a potential role has also been described for GI neoplastic diseases, including colorectal and pancreatic cancer. Different mechanisms of action have been proposed, ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic over the last year.

Looking for celiac disease in Italian women with endometriosis: a case control study.

In the last years, a potential link between endometriosis and celiac disease has been hypothesized since these disorders share some similarities, specifically concerning a potential role of oxidative stress, inflammation, and immunological dysfunctions. We investigated the prevalence of celiac disease among Italian women with endometriosis with respect to general population. Consecutive women with a laparoscopic and histological confirmed diagnosis of endometriosis were enrolled; female nurses of our institution, without a known history of endometriosis, were enrolled as controls. IgA endomysial and tissue transglutaminase antibodies measurement and serum total IgA dosage were performed in both groups. An upper digestive endoscopy with an intestinal biopsy was performed in case of antibodies positivity. Presence of infertility, miscarriage, coexistence of other autoimmune diseases, and family history of autoimmune diseases was also investigated in all subjects. Celiac disease was diagnosed in 5 of 223 women with endometriosis and in 2 of 246 controls (2.2% versus 0.8%; P = 0.265). Patients with endometriosis showed a largely higher rate of infertility compared to control group (27.4% versus 2.4%; P < 0.001). Our results confirm that also in Italian population an increased prevalence of celiac disease among patients with endometriosis is found, although this trend does not reach the statistical significance.

Colon cancer stem cells: controversies and perspectives.

Tumors have long been viewed as a population in which all cells have the equal propensity to form new tumors, the so called conventional stochastic model. The cutting-edge theory on tumor origin and progression, tends to consider cancer as a stem cell disease. Stem cells are actively involved in the onset and maintenance of colon cancer. This review is intended to examine the state of the art on colon cancer stem cells (CSCs), with regard to the recent achievements of basic research and to the corresponding translational consequences. Specific prominence is given to the hypothesized origin of CSCs and to the methods for their identification. The growing understanding of CSC biology is driving the optimization of novel anti-cancer targeted drugs.

Gastric non-secreting neuroendocrine tumor and hypochlorhydria-related hypergastrinemia: a case report.

INTRODUCTION: Zollinger-Ellison syndrome is characterized by recurrent peptic ulcers and diarrhea that result from gastrin-secreting neuroendocrine tumors of the gastrointestinal tract; nevertheless, severe hypergastrinemia may also have alternative pathogenetic explanations. CASE PRESENTATION: A 61-year-old woman of Caucasian origin presented with a history of epigastric pain and early satiety, severe hypergastrinemia (approximately 2000 pg/mL) and a neuroendocrine polyp in the corpus of her stomach. Chronic atrophic gastritis and intestinal metaplasia was present, but she denied use of acid suppressant drugs and the results of tests for Helicobacter pylori as well as gastric parietal cell and intrinsic factor antibodies were negative. She underwent a radical gastric tangential resection. Six months later, serum gastrin was still elevated despite lack of recurrence of tumor. CONCLUSION: The clinical picture was suggestive for a hypochlorhydria-related hypergastrinemia with subsequent development of a non-secreting carcinoid. We suggest a periodic endoscopic follow-up in patients with severe hypochlorhydria-related hypergastrinemia in order to earlier detect neuroendocrine polyps.

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases.

AIM: To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. METHODS: Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. RESULTS: All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P < 0.01) after treatment. Only patients with UC showed a significant reduction of DAI, from a median 6.5 (IQR: 4-9) before treatment to 2 (IQR: 1-3) after treatment (P < 0.01). Conversely, in CD patients, although displaying a clear reduction of DAI from 7 (IQR: 5.5-7.5) before therapy to 1.5 (IQR: 0.5-2.5) after therapy, differences observed were not significant (P = 0.06). Seventy-nine percent (SE 11%) of patients showed improvement of HI of at least 1 point, while only one CD and two UC patients showed HI stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant). The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients. No side effects were reported during treatment or at 4 wk follow-up visit. CONCLUSION: PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD patients.

Food fried in extra-virgin olive oil improves postprandial insulin response in obese, insulin-resistant women.

The benefits of low glycemic load (GL) diets on clinical outcome in several metabolic and cardiovascular diseases have extensively been demonstrated. The GL of a meal can be affected by modulating the bioavailability of carbohydrates or by changing food preparation. We investigated the effect on plasma glucose and insulin response in lean and obese women of adding raw or fried extra-virgin olive oil to a carbohydrate-containing meal. After an overnight fast, 12 obese insulin-resistant women (body mass index [BMI], 32.8 ± 2.2 kg/m(2)) and five lean subjects (BMI, 22.2 ± 1.2 kg/m(2)) were randomly assigned to receive two different meals (designated A and B). Meal A was composed of 60 g of pasta made from wheat flour and 150 g of grilled courgettes with 25 g of uncooked oil. Meal B included 15 g of oil in the 150 g of deep-fried courgettes and 10 g of oil in the 60 g of stir-fried pasta. Both meals included 150 g of apple. Blood samples were collected at baseline and every 30 minutes over a 3-hour post-meal period and were tested for levels of glucose, insulin, C-peptide, and triglycerides. The area under the curve (AUC) values were calculated. In obese women the AUCs for C-peptide were significantly higher after meal A than after meal B at 120 minutes (W [Wilcoxon sign rank test] = 27.5, P = .0020), 150 minutes (W = 26.5, P = .0039), and 180 minutes (W = 26.5, P = .0039). No differences were found in lean subjects. This study demonstrated that in obese, insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal.

Therapeutic implications of mesenchymal stem cells in liver injury.

Mesenchymal stem cells (MSCs), represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

Stem cell-based therapies for liver diseases: state of the art and new perspectives.

Millions of patients worldwide suffer from end-stage liver pathologies, whose only curative therapy is liver transplantation (OLT). Given the donor organ shortage, alternatives to OLT have been evaluated, including cell therapies. Hepatocyte transplantation has been attempted to cure metabolic liver disorders and end-stage liver diseases. The evaluation of its efficacy is complicated by the shortage of human hepatocytes and their difficult expansion and cryopreservation. Recent advances in cell biology have led to the concept of "regenerative medicine", based on the therapeutic potential of stem cells (SCs). Different types of SCs are theoretically eligible for liver cell replacement. These include embryonic and fetal SCs, induced pluripotent cells, annex SCs, endogenous liver SCs, and extrahepatic adult SCs. Aim of this paper is to critically analyze the possible sources of SCs suitable for liver repopulation and the results of the clinical trials that have been published until now.

Role of trait anxiety in persistent radicular pain after surgery for lumbar disc herniation: a 1-year longitudinal study.

OBJECTIVE: To evaluate anxiety and depression as prognostic factors for radicular and back pain after surgery in patients with lumbar disc herniation in a 1-year follow-up study. METHODS: A total of 108 patients with lumbar disc herniation were enrolled in the study. Anxiety was assessed by State and Trait Anxiety Inventory; current depression was assessed by Zung Self-Rating Depression Scale. Severity of pain was scored on the visual analog scale (VAS). The State and Trait Anxiety Inventory, Zung Self-Rating Depression Scale, and VAS were administered before surgery and 1, 3, 6, and 12 months after surgery. RESULTS: Before surgery, 72.2% of patients showed state anxiety, 54.6% of patients showed trait anxiety, and 11.1% of patients showed current depression. During the follow-up period, there was a significant decrease in the prevalence of state anxiety (P < .0001), no variation in the prevalence of trait anxiety (P = .115), and a significant increase in the prevalence of current depression (P = .002). Linear regression analysis showed that the presence of trait anxiety before surgery was the main determinant of the presence of pain after surgery (P < .0001). VAS scores were evaluated by dividing patients into 2 groups based on the presence or absence of trait anxiety before surgery. The subgroup affected by trait anxiety before surgery had significantly higher VAS scores at each follow-up assessment compared with patients without trait anxiety (P < .0001). CONCLUSION: The presence of trait anxiety before surgery is a prognostic factor for the persistence of pain after surgery.

Biofilm demolition and antibiotic treatment to eradicate resistant Helicobacter pylori: a clinical trial.

BACKGROUND & AIMS: Helicobacter pylori attaches to gastric mucosa and grows as a biofilm. This constitutes protection from antimicrobial agents. We assessed the role of a pretreatment with n-acetylcysteine in destroying biofilm and overcoming H pylori antibiotic resistance. METHODS: In an open-label, randomized controlled trial, 40 subjects with a history of at least 4 H pylori eradication failures were evaluated for biofilm presence, antibiotic susceptibility, and H pylori genotypes. Subjects were assigned randomly to receive (group A) or not (group B) n-acetylcysteine before a culture-guided antibiotic regimen. The primary end point was the H pylori eradication rate as assessed by (13)C-labeled urea breath testing. RESULTS: H pylori was eradicated in 13 of 20 (both per-protocol and intention-to-treat analyses, 65%; 95% confidence interval, 44%-86%) group A participants and 4 of 20 (both per-protocol and intention-to-treat analyses, 20%; 95% confidence interval, 3%-37%) group B participants (P < .01). Biofilms persisted only in unsuccessfully treated participants. H pylori genotypes did not influence treatment outcome. CONCLUSIONS: N-acetylcysteine pretreatment before a culture-guided antibiotic regimen is effective in overcoming H pylori antibiotic resistance.

[Focal myocarditis mimicking ST-elevation myocardial infarction in a patient with Helicobacter pylori infection: role of magnetic resonance with late gadolinium enhancement]. / Miocardite simulante un infarto miocardico acuto con sopraslivellamento del tratto ST in paziente con infezione da Helicobacter pylori: ruolo della risonanza magnetica con late gadolinium enhancement.

Myocarditis is an emerging disease. We have investigated a case of focal myocarditis with ventricular thrombus in a patient with Helicobacter pylori infection who came to our attention for the persistence of chest pain one week after previous discharge. The patient was before and otherwise misunderstood as myocardial infarction and recognized in our Centre as myocarditis by magnetic resonance. Diagnostic iter was focused on understanding the pathogenesis of the previous reported cardiac event as well as a link with the persistence of chest pain finally found related to Helicobacter pylori infection. We briefly discuss about role and some caveats of magnetic resonance with late gadolinium enhancement as new diagnostic approach of myocarditis, compared to myocardial biopsy.

[Helicobacter pylori infection: from gastric to systemic disease]. / Manifestazioni extragastriche dell'infezione da Helicobacter pylori.

H. pylori infection, through a chronic stimulation of the immune system and the occurrence of molecular mimicry mechanisms, is responsible for the majority of the gastroduodenal diseases and also for some extragastric disorders, including sideropenic anemia and idiopathic thrombocytopenic purpura; other diseases are under investigation.

Percutaneous laser ablation of hepatocellular carcinoma in patients with liver cirrhosis awaiting liver transplantation.

OBJECTIVE: The aim of this study was to determine the effectiveness and safety of percutaneous laser ablation for the treatment of cirrhotic patients with hepatocellular carcinoma awaiting liver transplantation. MATERIALS AND METHODS: The data of 9 male cirrhotic patients (mean age 50 years, range 45-60 years) with 12 biopsy proven nodules of hepatocellular carcinoma (mean diameter 2.0 cm, range 1.0-3.0 cm) treated by laser ablation before liver transplantation between June 2000 and January 2006 were retrospectively reviewed. Laser ablation was carried out by inserting 300 nm optical fibers through 21-Gauge needles (from two to four) positioned under ultrasound guidance into the target lesions. A continuous wave Neodymium:Yttrium Aluminium Garnet laser was used. Transarterial chemoembolization prior to liver transplantation was performed in two incompletely ablated tumors. RESULTS: No procedure-related major complications were recorded. During the waiting time to liver transplantation local tumor progression after ablation occurred in 3 nodules (25%). At histological examination of the explanted livers complete necrosis was found in 8 nodules (66.7%, all treated exclusively with laser ablation), partial necrosis >50% in 3 nodules (25%), and partial necrosis <50% in 1 nodule. CONCLUSION: In patients with cirrhotic livers awaiting liver transplantation, percutaneous laser ablation is safe and effective for the management of small hepatocellular carcinoma.

Role of the tumor necrosis factor antagonists in the treatment of inflammatory bowel disease: an update.

Crohn's disease and ulcerative colitis represent the two major forms of inflammatory bowel disease (IBD). Recent research points out the role of uncontrolled intestinal inflammation in the pathogenesis of IBD. Therefore, there is a growing interest in developing novel biologic therapies targeting specific molecules of the inflammatory cascade. Among them, anti-tumor necrosis factor (anti-TNF) agents (i.e. infliximab, adalimumab, certolizumab pegol) have proved to be effective, particularly for patients with refractory IBD. These biological therapies have changed, at least partially, the clinical course and medical management of IBD. However, the administration of anti-TNF drugs has also been associated with serious side-effects, which have raised concerns on the application of these drugs in clinical practice. The goal of this review is to provide an update and analyze the pros and cons of using anti-TNF therapies in the treatment of IBD.

Increased serum high-density lipoprotein-cholesterol concentration in celiac disease after gluten-free diet treatment correlates with body fat stores.

BACKGROUND: Low high-density lipoprotein-cholesterol (HDL-C) concentration correlates with increased cardiovascular risk. A great prevalence of celiac disease (CD) was reported among patients with low HDL-C concentration, and gluten-free diet (GFD) treatment seems to normalize lipid profile. We evaluated blood lipids and body composition in 26 CD patients with low HDL-C level (<1.0 mmol/L) at diagnosis and after GFD. STUDY: A case-control study. METHODS: The diagnosis was based on histologic evidence of subtotal or total duodenal villous atrophy. Patients were studied before and after GFD treatment (14.2+/-1.4 mo) with biopsy-proven return to normal of the duodenal mucosa. HDL-C was enzymatically assessed after precipitation of very low-density lipoprotein and low-density lipoprotein with heparin-magnesium. Apolipoprotein (Apo)-AI level was assessed by immunoturbidimetric assay; triglycerides by an enzymatic colorimetric method. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS: Body composition improved after GFD, with increasing body weight (P<0.05) essentially owing to increased fat mass (FM) (P<0.01), rather than fat-free mass (P=0.064). Total cholesterol and HDL-C were lower in untreated compared with treated patients (P<0.001 and P<0.0001). Apo-AI level increased significantly after GFD (1.20+/-0.22 vs. 1.46+/-0.17 g/L; P<0.0001). Apo-AI, sex, and FM were all significant determinants of HDL-C level; a positive correlation (R=0.68; P<0.0001) was found between increase in HDL-C level and in FM after GFD treatment. CONCLUSIONS: Restoration of lipid profile in CD patients after GFD treatment may be explained by an increase in both Apo-AI secretion by intestinal cells and body fat stores.