Long versus short peroral endoscopic myotomy for the treatment of achalasia: results of a non-inferiority randomised controlled trial.

OBJECTIVE: Peroral endoscopic myotomy (POEM) has become standard treatment for achalasia with comparable efficacy to surgery. In most of published series, the length of myotomy is 12-13 cm. Shorter cuts could have the advantage of shorter procedure time and possibly reduced gastro-oesophageal reflux disease (GORD) rate. DESIGN: This single-centre, patient-blinded, randomised, non-inferiority clinical trial included 200 patients, who were randomly allocated, to receive either a long-POEM (13 cm; 101 patients) or a short-POEM (8 cm; 99 patients). Primary outcome was defined as an Eckardt symptom score of ≤3 at 24 months after the procedure; a non-inferiority design was chosen with an accepted success range of 6% between the two treatments. Secondary outcomes included operating time, complication rate, postoperative manometry, GORD rate and quality of life. RESULTS: In the intention-to-treat analysis, clinical success rates were 89.1% in the long-POEM and 98.0% in the short-POEM group, resulting in an absolute between-group difference of -8.9% (90% CI -14.5 to -3.3).Procedure time was significantly reduced in the short-POEM as compared with the long-POEM group (40 vs 50 min, p<0.0001). Severe adverse events occurred in one patient in both groups.No differences were observed in postoperative GORD: acid exposure >6% on pH monitoring study at 6 months was seen in 34.3% (long-POEM) vs 31.1% (short-POEM), while endoscopic oesophagitis was diagnosed in 37.6% vs 51.5% at 6 months and in 21% vs 24.5% at 24 months. Regular proton pump inhibitor use was not different either (36.8% vs 37.5%). CONCLUSIONS: Our study demonstrates non-inferiority of a shorter cut length of POEM as compared with the standard treatment, which saved some procedural time. GORD rate was not reduced by reducing cutting length. TRIAL REGISTRATION NUMBER: NCT03450928.

Poem Versus Laparoscopic Heller Myotomy in the Treatment of Esophageal Achalasia: A Case-Control Study from Two High Volume Centers Using the Propensity Score.

BACKGROUND: POEM has recently had a widespread diffusion, aiming at being the treatment of choice for esophageal achalasia. The results of ongoing RCTs against laparoscopic myotomy are not available, yet. We, therefore, designed this propensity score (PS) case-control study with the aim of evaluating how POEM compares to the long-standing laparoscopic Heller myotomy + Dor fundoplication (LHD) and verifying if it may really replace the latter as the first-line treatment for achalasia. METHODS: Two groups of consecutive patients undergoing treatment for primary achalasia from January 2014 to November 2017 were recruited in two high-volume centers, one with extensive experience with POEM and one with LHD. Patients with previous endoscopic treatment were included, whereas patients with previous LHD or POEM were excluded. A total of 140 patients in both centers were thus matched. LHD and POEM were performed following established techniques. The patients were followed with clinical (Eckardt score), endoscopic, and pH-manometry evaluations. RESULTS: The procedure was successfully completed in all the patients. POEM required a shorter operation time and postoperative stay compared to LHD (p < 0.001). No mortality was recorded in either group. Seven complications were recorded in the POEM group (five mucosal perforations) and 3 in the LHD group (3 mucosal perforations)(p = 0.33). Two patients in the POEM group and one in the LHD were lost to follow-up. One patient in both groups died during the follow-up for unrelated causes. At a median follow-up of 24 months [15-30] for POEM and 31 months [15-41] for LHD (p < 0.05), 99.3% of the POEM patients and 97.7% of the LHD patients showed an Eckardt score ≤ 3 (p < 0.12). Four years after the treatment, the probability to have symptoms adequately controlled was > 90% for both groups (p = 0.2, Log-rank test). HR-Manometry showed a similar reduction in the LES pressure and 4sIRP; 24-h pH-monitoring showed however an abnormal exposure to acid in 38.4% of POEM patients, as compared to 17.1% of LHD patients (p < 0.01) and esophagitis was found in 37.4% of the POEM and 15.2% of LHD patients (p < 0.05). CONCLUSION: POEM provides the same midterm results as LHD. This study confirms, however, a higher incidence of postoperative GERD with the former, even if its real significance needs to be further evaluated.

Eosinophilic oesophagitis (in nickel-allergic patient) regressed after nickel oral desensitization: A case report.

The eosinophilic oesophagitis (EoE) is a chronic immune/antigen disorder of the oesophagus clinically characterized by dysphagia and pathologically by mucosa eosinophilic infiltration. Th2-type allergic reactions are considered having important roles in the aetiopathogenesis of EoE. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the oesophagus are the most important treatments. 'Systemic nickel allergy syndrome' (SNAS) interests about 20% of patients with nickel contact allergy which could present systemic cutaneous manifestations (urticaria, oedema, etc.) and also respiratory and digestive symptoms (meteorism, abdominal pain, diarrhoea, etc.). In the literature, it is demonstrated that nickel oral immunotherapy is effective in reducing symptoms of SNAS and in modulating inflammatory parameters. We describe the case of a 48-year-old woman suffering from EoE not responsive to the topical steroid administration and diagnosis of SNAS. The patient started nickel oral desensitization according to the literature protocol continuing nickel-free diet. After 1 year from the beginning of the treatment, during the maintenance dose (500 ng three times a week), she decreased gradually the dosage of immunotherapy and reintroduced all the culprit foods. After the immunotherapy interruption, during the free diet, she repeated the oesophagogastroscopy with a complete macroscopic and histological resolution. We showed the first case of an EoE in a patient affected by SNAS responsive to the nickel-free diet and the oral immunotherapy.

Screening of colorectal cancer: present and future.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in males and second in females, and the fourth most common cause of cancer death worldwide. Currently, about 60-70% of diagnosed cases in symptomatic patients are detected at an advanced stage of disease. Earlier stage detection through the use of screening strategies would allow for better outcomes in terms of reducing the disease burden. Areas covered: The aim of this paper is to review the current published evidence from literature which assesses the performance and effectiveness of different screening tests for the early detection of CRC. Expert commentary: Adequate screening strategies can reduce CRC incidence and mortality. In the last few decades, several tests have been proposed for CRC screening. To date, there is still insufficient evidence to identify which approach is definitively superior, and no screening strategy for CRC can therefore be defined as universally ideal. The best strategy would be the one that can be economically viable and to which the patient can adhere best to over time. The latest guidelines suggest colonoscopy every 10 years or annual fecal immuno-chemical test (FIT) for people with normal risk, while for individuals with high risk or hereditary syndromes specific recommendations are provided.

Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C.

Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylated-interferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.

Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update.

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the "forgotten organ", Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor(®) (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN.

Gut microbiota in autism and mood disorders.

The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.

Coeliac disease: an old or a new disease? History of a pathology.

The celiac disease is an ancient pathology, present since the introduction of the wheat in the diet, of which the first description of the compatible clinical symptoms and signs goes back to 250 A.D. Today it is known that the expression of this pathology is multifaceted, ranging from clinical features indicative of bowel disease and malabsorption, until symptoms once unexpected, because of their extra-digestive clinical features. With our work, we wanted to retrace the history of this disease, correlating it with the intake of gluten present in wheat after cooking , ever since mankind has increased the cultivation of cereals. Re-evaluating the clinical and instrumental methods for the diagnosis of Celiac Disease, and benefitting from the most modern techniques for the morphological, biochemical and genetic study of the patients, we sought to understand whether the incidence of the disease is actually increased or if has been considered less frequent for the lower valuation of the signs once deemed more atypical, but currently considered preliminary indicative of the pathology, for its association with other autoimmune diseases, and for the study of some genetic and familiar characteristics. Each of these factors has led the modern medicine to increase epidemiological studies and expand the research potential carriers of celiac disease with safer diagnostic tests.

Gut microbial flora, prebiotics, and probiotics in IBD: their current usage and utility.

Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn's disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the "forgotten organ", gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD.