Efficacy and tolerability of a novel galactomannan-based formulation for symptomatic treatment of gastroesophageal reflux disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Proton Pump Inhibitors (PPIs) and traditional antacids are the common standard set of therapy for the management of gastroesophageal reflux disease (GERD) symptoms. The aim of the current study was to evaluate efficacy and safety of a novel galactomannan-based liquid formulation in reducing typical GERD symptoms in patients not taking PPIs. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, placebo-controlled study. Sixty patients met the eligibility criteria and were treated either with the investigational product (RefluG™) or placebo, one sachet three times per day for 14 consecutive days. Symptom intensity/frequency and quality of life were assessed over the course of the study by Reflux Disease Questionnaire (RDQ) and GERD-Health related Quality of life (HRQL) Questionnaire, respectively. The primary endpoint was to determine the number of subjects with at least 30% symptoms reduction from baseline to day 14 compared to placebo. RESULTS: RefluG™ was statistically superior to placebo (p <0.001) as 100% of subjects experienced at least 30% symptoms reduction at the end of the study while none achieved a 30% reduction in the placebo group. For all domains both after 7 and 14 days of treatment, significant improvement in HRQL was seen in the active group in comparison to placebo. Tolerability and safety were good and comparable between groups. CONCLUSIONS: The investigational product was safe and effective as mono-therapy in providing early resolution of troublesome GERD symptoms as well as for improving quality of life.

Large diameter fully covered self-expanding metal stent placement for palliation of proximal malignant esophageal strictures.

In patients with malignant esophageal strictures within 6 cm from the upper esophageal sphincter, self-expanding metal stents placement represents a challenge because there is an increased risk of complications. The aim of this study was to assess the safety and effectiveness of large-diameter WallFlex(®) fully covered self-expanding metal stents for palliation of patients with proximal malignant esophageal strictures. From March 2010 to December 2012, 12 patients with proximal strictures (4-6 cm from the upper esophageal sphincter) and six with very proximal strictures (<4 cm from the upper esophageal sphincter) were palliated with this fully covered self-expanding metal stent and included in the study. Technical success was 100% and clinical success was 94%. The mean baseline dysphagia score was 3.2, and 1 week after stenting it improved significantly to 1.3 (P < 0.001). Early complications occurred in four patients, more frequently in patients with very proximal strictures as compared with patients with proximal strictures (P = 0.02). Late complications occurred in five patients, and there were no differences between patients with very proximal strictures or proximal strictures (P = 0.245). The mean survival after stent placement was 119 days, and no differences between patients with very proximal strictures versus proximal strictures were found (P = 0.851). There was no stent-related mortality or 30-day mortality. Our results suggested that a large-diameter fully covered self-expanding metal stent is an effective and secure device for palliation of patients with proximal malignant esophageal strictures.

Serum adipokine levels in overweight patients and their relationship with non-alcoholic fatty liver disease.

AIM: Non-alcoholic fatty liver disease (NAFLD) is a relevant public health matter in Western countries. The pathogenetic link between visceral fat, insulin resistance (IR) and NAFLD has been reported in literature. However, there are contradictions on the changes of adipokine levels in serum related to the presence of NAFLD. The aim of the present study was to evaluate the serum concentrations of a selected set of adipokines, that is, adiponectin, leptin, resistin and the pro-inflammatory cytokine interleukin-6 (IL-6) in overweight patients, and to clarify their relationship with NAFLD. METHODS: Fasting serum levels of adipokines were determined in 42 consecutive overweight patients and in 25 lean controls. The degree of ultrasound (US) liver steatosis was graded according to the Hamaguchi score. RESULTS: Liver steatosis was detected in 33 patients (78%) by US examination. Twelve patients with elevated transaminases levels showed significantly higher values of IR, leptin and resistin levels (P<0.05). Patients with steatosis presented a significantly higher leptin and a lower adiponectin levels (P<0.05) than controls. A significant inverse correlation was found between US steatosis progression and adiponectin and resistin levels (p<0.05). Considering the multiple logistic regression, adiponectin and leptin were good predictors to detect the presence of steatosis (p<0.05). CONCLUSION: Our data support the concept that adipokine level changes are closely linked with IR. In addition, serum adiponectin and leptin levels may be used as diagnostic markers to determine the presence of NAFLD in overweight patients.

GastroPanel® test for non-invasive diagnosis of atrophic gastritis in patients with dyspepsia.

AIM: Atrophic gastritis (AG), first step in the cascade leading to gastric adenocarcinoma, is related to Helicobacter pylori (H. pylori) infection. Currently, the gold standard for the diagnosis of AG is esophagogastroduodenoscopy (EGD) with histological examination of the biopsy specimens. However, since the latter are taken in random order and the distribution of AG is often patchy, histology is only representative of mucosal status. Considering this limitation, a test named GastroPanel®, that measures the blood concentrations of pepsinogen I and II, gastrin-17 and H. pylori antibodies, has been developed as a potential non-invasive biopsy. Aim of this study has been to assess the accuracy of GastroPanel® in patients with AG. METHODS: Forty-seven dyspeptic patients (24 males, mean age 52.2±9.3 years), in follow-up for antral or diffuse AG, were enrolled. All underwent at least two EGDs with random biopsies and blood collection for GastroPanel® parameters examination. RESULTS: Of the 47 patients, 16 (34.1%) had histological diagnosis of antral and 31 (65.9%) multifocal AG; 17 (36.2%) patients had mild and 30 (63.8%) had moderate-severe AG. H. pylori was detected in 39 (82.9%) and intestinal metaplasia was found in all patients. GastroPanel® showed 82.9% sensitivity for the diagnosis of AG and 53.8% for the diagnosis of H. pylori infection. The prediction of advanced atrophy was not sufficiently accurate, neither in patients with antral nor in those with multifocal AG. CONCLUSION: GastroPanel® can be useful for detecting patients with AG. However, it does not reflect the severity of atrophy.

Liver steatosis in celiac disease: the open door.

Non-alcoholic fatty liver disease (NAFLD) is a common disease of unknown origin characterized by histological features similar to alcoholic-like liver injury but in the absence of significant alcohol intake. Non-alcoholic fatty liver disease refers to a spectrum of diseases of the liver ranging from simple steatosis (i.e., fatty infiltration of the liver) to nonalcoholic steatohepatitis (i.e., steatosis with inflammation and hepatocyte necrosis) to cirrhosis. Non-alcoholic fatty liver disease is frequently associated with disorders such as insulin resistance, obesity, type 2 diabetes mellitus, hyperlipidemia and protein-calorie malnutrition. However, in a subgroup of NAFLD patients, the true relevant cause remains undetermined. Celiac disease (CD) is a common immune-mediated disorder and develops in genetically susceptible subjects after the ingestion of gluten proteins. Celiac disease has been found in about 10% of patients with unexplained abnormal liver tests, and in about 3.5% of patients with NAFLD as the only manifestation of the disease. The frequency of subclinical or silent presentations in older children and adults highlights the importance of CD screening in patients with unexplained chronic abnormal liver function tests and NAFLD without any specific etiology. The pathogenesis of liver steatosis in CD is uncertain. The aims of this review are to describe the possible mechanisms involved in the occurrence and progression of liver steatosis in CD patients.

The Gastro-Laryngeal Tube for interventional endoscopic biliopancreatic procedures in anesthetized patients.

The Gastro-Laryngeal Tube (G-LT) is a modification of the laryngeal tube which provides a dedicated channel for the insertion of an endoscope while acting as a supraglottic airway for ventilation. The aim of this study was to assess the safety and effectiveness of this device in patients undergoing anesthesia for interventional endoscopic biliopancreatic procedures (IEBPPs).A total of 22 patients were included in the study. The G-LT was inserted successfully in all patients. Arterial oxygen saturation was stable; the mean value was 97.9%. The IEBPPs were performed successfully in all patients through the endoscopic channel, with a mean duration of 99 minutes. The maneuverability of the endoscope was considered good in all patients. There were two cases of sore throat after the procedures, two cases of asymptomatic erosion of the upper esophageal mucosa, one case of Mallory-Weiss syndrome, and one case of pancreatitis after endoscopic retrograde cholangiopancreatography.Our results suggest that the G-LT is an effective and secure device for airway management and for use during IEBPPs.

Insulin-like growth factor-II is a useful marker to detect hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The utility of serum alpha-fetoprotein (α-FP) in its detection is questionable. Over-expression and high circulating levels of insulin-like growth factor-II (IGF-II) were reported in tissue and in serum of patients with HCC. We investigated the diagnostic application of IGF-II in the diagnosis of HCC. METHODS: Serum IGF-II and α-FP levels were measured in 178 patients (82 with HCC and 96 with liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric combination test and confidence interval analysis were used for statistical evaluation of data. RESULTS: The best cut-off values selected by ROC curves were 796 ng/ml for IGF-II and 132 ng/ml for α-FP. IGF-II mean values were higher in patients with HCC than in those with liver cirrhosis (LC) (p=0.0001) but lower in LC than in controls (p=0.0001). Serum IGF-II levels above cut-off were found in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of controls. α-FP serum levels >132 ng/ml were observed in 48% of HCC, in 3.1% of LC and in none of control group. By correlation study, serum IGF-II levels were significantly correlated with serum α-FP levels (r=0.427, p=0.0001) and with nodules' diameter (r=0.252, p=0.0130) but not with nodules' number (p>0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive values than α-FP. CONCLUSION: Circulating IGF-II is not a useful marker for HCC. Further researches are however needed to evaluate its diagnostic accuracy before and after nutritional adjustment.

Cholangioscopy using a new type of cholangioscope for the diagnosis of biliary tract disease: a case series.

We present an initial report regarding the clinical usefulness of peroral cholangioscopy, using a new type of cholangioscope, the Polyscope. Peroral cholangioscopy was performed in four patients with strictures after orthotopic liver transplantation (OLT) which were suspected of being ischemic biliary lesions, in three with indeterminate biliary strictures, in three with suspected retained bile duct stones, and in two for evaluation of the intraductal spread of adenomatous tissue after an ampullectomy. In all cases peroral cholangioscopy was performed successfully without complications. On the basis of direct viewing and/or tissue sampling a correct diagnosis was reached in all cases: in all patients who underwent OLT the strictures were not ischemic; the indeterminate strictures were all benign; and, in patients with suspected stones, complete clearance was confirmed. Intraductal spread was confirmed in one patient and excluded in the other. In our experience, peroral cholangioscopy using a Polyscope is a safe and effective method for diagnosing bile duct lesions.

Endoscopic ultrasound-guided transmural drainage of infected pancreatic fluid collections with placement of covered self-expanding metal stents: a case series.

Endoscopic ultrasound-guided transmural drainage (EUS-GTD) has become the standard procedure for treating symptomatic pancreatic fluid collections. The aim of this series was to evaluate the efficacy and safety of covered self-expanding metal stent (CSEMS) placement for treating infected pancreatic fluid collections. From January 2007 to May 2010, 22 patients (18 M/4F; mean age 56.9) with infected pancreatic fluid collections (mean size, 13.2 cm) at two Italian centers were evaluated for EUS-GTD. In 20 of the 22 patients, EUS-GTD with CSEMS placement was indicated. Early complications occurred in two patients: one patient developed a superinfection, which was managed conservatively, and one experienced stent migration and superinfection, and was managed surgically. The CSEMSs were removed without difficulty in 18 patients after a median of 26 days, while stent removal failed in one patient due to inflammatory tissue ingrowth; instead it was removed during surgery performed for renal cancer. Clinical success was achieved without additional intervention in 17 patients during a mean follow-up of 610 days; only one symptomatic recurrence was observed. In our experience, EUS-GTD with CSEMS placement appears safe for the treatment of infected pancreatic fluid collections.

Molecular findings on Helicobacter pylori: update for clinicians.

Helicobacter pylori (H. pylori) is a gram-negative bacterium which is responsible for a wide range of disorders of the stomach, from chronic gastritis to peptic ulcers to gastric cancer which, however, occurs in a lower percentage of subjects. The difference in the clinical course of infection seems to be correlated both to the typical pathogenicity of the bacterium and to factors related to the host. The reasons underlying these observations include differences in bacterial pathogenicity as well as in host susceptibility. Numerous studies published in the last year have provided new insights into H. pylori virulence factors, their interaction with the host and the relative consequences in the pathogenesis. In this review, we have set ourselves the target of summarising the latest progress made in understanding the molecular aspects of H. pylori infection of notable importance for the physician.

Carbon dioxide insufflation versus air insufflation during endoscopic retrograde cholangiopancreatography under general anesthesia.

AIM: The aim of this paper was to evaluate the effect of carbon dioxide (CO2) vs. air insufflation on post-endoscopic retrograde cholangiopancreatography (ERCP) abdominal pain and distension. In addition, we investigated the changes in the partial pressure of end-tidal CO2 (PetCO2) and the partial pressure of arterial CO2 (PaCO2). METHODS: From October 2009 to January 2010, all patients admitted to our centre for ERCP were screened for enrollment; the patients recruited were randomised to CO2 or air insufflation. The patients were asked to rate their abdominal pain intensity and distension using a 100-mm Visual Analogue Scale (VAS) before, in the recovery room and at 1, 3, 6 and 24 hours after the ERCP. All anesthesiological and endoscopic details and complications were evaluated. RESULTS: We included 76 patients, 39 in the Air group and 37 in the CO2 group. The groups were similar for age, gender, indications and duration of the procedure. Post-procedure mean values of pain (in the recovery room and at 1, 3 and 6 hours) and distension (at recovery room, and at 1 and 3 hours) according to the VAS were significantly reduced in the CO2 group as compared to the Air group. At baseline, the PetCO2 values were similar between the two groups while, during the ERCP, they increased significantly in CO2 group as compared to the Air group; these values were reduced by simply increasing the ventilation. CONCLUSION: CO2 insufflation during ERCP significantly reduces post-procedural abdominal pain and distension. Increased PetCO2 and PaCO2 values remained within acceptable or readily controllable ranges.

Complications of endoscopic ultrasonography.

Since its development in the 1980s, endoscopic ultrasonography (EUS) has undergone a great deal of technological modifications. EUS has become an important tool in the evaluation of patients with various clinical disorders and is increasingly being utilized in many centers. EUS has been evolving over the years; EUS-guided fine needle aspiration (FNA) for cytological and/or histological diagnosis has become standard practice and a wide array of interventional and therapeutic procedures are performed under EUS guidance for diseases which otherwise would have needed surgery, with its associated morbidities. EUS shares the risks and complications of other endoscopic procedures. This article addresses the specific adverse effects and risks associated with EUS, EUS-FNA and interventional EUS, namely perforation, bleeding, pancreatitis and infection. Measures to help minimizing these risks will also be discussed.

EUS-guided biliary drainage with placement of a new partially covered biliary stent for palliation of malignant biliary obstruction: a case series.

Endoscopic ultrasonography-guided biliary drainage (EUS-BD) has been developed as an alternative drainage technique in patients with obstructive jaundice where endoscopic retrograde cholangiopancreatography (ERCP) has failed. Between July 2008 and December 2009, 16 patients (9 men; median age 79 years) with biliopancreatic malignancy, who were candidates for alternative techniques of biliary decompression because ERCP had been unsuccessful, underwent EUS-BD with placement of a transmural or transpapillary partially covered nitinol self-expandable metal stent (SEMS). EUS-assisted cholangiography was successful in all patients, with definition of the relevant anatomy, but biliary drainage was successfully performed in only 12 (75 %) of the 16 patients (9 choledochoduodenostomies with SEMS placement and 3 biliary rendezvous procedures with papillary SEMS placement), with regression of the cholestasis. No major complications and no procedure-related deaths occurred. There was one case of pneumoperitoneum which was managed conservatively. The median follow-up was 170 days. During the follow-up, eight patients of the 12 patients in whom biliary draining was successful died; four are currently alive. None of the patients required endoscopic reintervention. This series demonstrated that EUS-BD with a partially covered SEMS has a high rate of clinical success and low complication rates, and could represent an alternative choice for biliary decompression.

Short- and long-term outcomes of self-expanding metal stent placement as a bridge to surgery for acute left-sided colorectal cancer obstruction.

AIM: The aim of this study was to evaluate the short- and long-term outcomes of self-expanding metal stent (SEMS) insertion as a bridge to surgery (BTS) in patients presenting with acute left-sided colorectal cancer obstruction (LCCO). METHODS: All patients with acute LCCO who underwent endoscopic SEMS placement as a BTS between January 2005 and December 2010 were reviewed and included in the study. RESULTS: Thirty-six patients (19M and 17F; mean age 68.5) were included. The most frequent location was the sigmoid colon (47.2%). Technical success was achieved in 91.6% and clinical success in 88.9%. Technical failure was related to the location of the stricture at the rectosigmoid junction (P=0.03). There were four SEMS-related complications: one fecal obstruction, one haemorrhage treated with APC and two silent perforations which were noted during surgical resection. The mean time between SEMS insertion and surgical treatment was 19 days (range 6-80 days) and the most frequent intervention was a left hemicolectomy (46.9%). No intraoperative mortality and morbidity, or postoperative mortality were observed. The postoperative morbidity rate was 18.8% (two wound infections, one deep venous thrombosis, one case of pneumonia and one anastomotic dehiscence). Finally, after discharge from hospital, a total of 29 patients (90%) were stoma free. At the end of the follow-up period, 24 patients are still alive and the mean survival rate was 37.3±18 months (range 9-72). CONCLUSION: In our experience, SEMS placement as a BTS is a safe and effective strategy for the treatment of patients with acute LCCO.