Showing papers in "Annals of Gastroenterology in 2014"

Molecular genetics of colorectal cancer.

Abstract: Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer.

The history of genetics in inflammatory bowel disease.

Abstract: The influence of genetics in the etiology of inflammatory bowel disease (IBD) was initially demonstrated by epidemiological data, including differences in prevalence among different ethnic groups, familial aggregation of IBD, concordance in twins, and association with genetic syndromes. These early observations paved the way to molecular genetics in IBD, and culminated in the identification of nucleotide-binding oligomerization domain containing 2 (NOD2) gene as an IBD risk gene in 2001. As in other complex diseases, the advent of Genome Wide Association studies has dramatically improved the resolution of the IBD genome and our understanding of the pathogenesis of IBD. However, the complexity of the genetic puzzle in IBD seems more pronounced today than ever previously. In total, 163 risk genes/loci have been identified, and the corresponding number of possible causal variants is challenging. The great majority of these loci are associated with both Crohn’s disease and ulcerative colitis, suggesting that nearly all of the biological mechanisms involved in one disease play some role in the other. Interestingly, a large proportion of the IBD risk loci are also shared with other immune-mediated diseases, primary immunodeficiencies and mycobacterial diseases.

Anti-reflux mucosectomy for gastroesophageal reflux disease in the absence of hiatus hernia: a pilot study.

Abstract: Background In our previous case report of circumferential mucosal resection for short-segment Barrett’s esophagus with high-grade dysplasia, symptoms of gastro-esophageal reflux disease (GERD) were significantly improved. This observation suggests that anti-reflux mucosectomy (ARMS) could represent an effective anti-reflux procedure, with the advantage that no artificial devices or prostheses would be left in situ.

Gastric MALT lymphoma: old and new insights.

Abstract: The stomach is the most frequent site of extranodal lymphoma. Gastric lymphoma originating from mucosa-associated lymphoid tissue (MALT) is typically a low-grade, B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori) infection. Only certain H. pylori strains in some predisposed patients determine lymphoma development in the stomach, according to a strain-host-organ specific process. The clinical presentation is poorly specific, symptoms ranging from vague dyspepsia to alarm symptoms. Similarly, different endoscopy patterns have been described for gastric lymphoma. H. pylori eradication is advised as first-line therapy in early stage disease, and complete lymphoma remission is achieved in 75% of cases. Neoplasia stage, depth of infiltration in the gastric wall, presence of the API2-MALT1 translocation, localization in the stomach, and patient ethnicity have been identified as predictors of remission. Recent data suggests that H. pylori eradication therapy may be successful for gastric lymphoma treatment also in a small subgroup (15%) of H. pylori-negative patients. The overall 5-year survival and disease-free survival rates are as high as 90% and 75%, respectively. Management of patients who failed to achieve lymphoma remission following H. pylori eradication include radiotherapy, chemotherapy and, in selected cases, surgery.

Sofosbuvir: a novel oral agent for chronic hepatitis C.

Abstract: Major changes have emerged during the last few years in the therapy of patients with chronic hepatitis C (CHC). Several direct acting antiviral agents (DAAs) have been developed showing potent activity against hepatitis C virus (HCV) and incrementally improving the rates of sustained virological response (SVR), even in difficult-to-treat CHC patients. Sofosbuvir, a new nucleotide analog, HCV NS5B polymerase inhibitor, represents the first key step towards the new era in the management of CHC, since it is the first approved DAA with excellent tolerability and favorable pharmacokinetic profile, limited potential for drug interactions, potent antiviral activity and high genetic barrier against all HCV genotypes. Sofosbuvir has recently become commercially available in combination with ribavirin, with or without pegylated interferon, achieving high SVR rates after 12-24 weeks of therapy. Finally, since interferon-free regimens are close to becoming the new standard of care in CHC patients, sofosbuvir has an ideal profile to be the cornerstone antiviral agent, especially in difficult-to-treat CHC patients, given in combination with other new DAAs. This review summarizes the main updated issues related to the efficacy and safety of sofosbuvir-containing regimens in CHC patients.

Psychological disorders in gastrointestinal disease: epiphenomenon, cause or consequence?

Abstract: Background Psychological disorders have been associated with irritable bowel syndrome (IBS) for decades in the absence of other objective etiology. However, such associations are also evident in other chronic diseases with more clearly defined pathogenesis such as ulcerative colitis. In this study, we examined the prevalence and severity of psychological disorders among IBS and ulcerative colitis (UC) patients relative to healthy controls. Methods A review was conducted of English-language literature to identify case-control studies reporting the prevalence of depression or anxiety in IBS and UC populations relative to healthy controls. Our primary endpoint was the pooled prevalence or average score of depression or anxiety in an IBS or UC population relative to healthy control. Results Seven case-control studies evaluating IBS and three evaluating UC were included. All IBS and UC studies reported excess prevalence and severity of depression as well as anxiety, relative to healthy controls. The prevalence of depression in excess of healthy controls was 39% in UC casecontrol trials and 33% in IBS studies, and excess anxiety was present in UC (42%) and IBS (19%) case-control trials as well. Anxiety and depression scores were higher (representing more severe symptoms) in both UC and IBS patients compared to healthy controls. Conclusions Anxiety and depressive disorders are associated with both IBS and UC. The nonspecific association between these psychological and gastrointestinal disorders could suggest that chronic gastrointestinal illness might affect psychosocial behavior.

C-reactive protein and bacterial infection in cirrhosis.

Abstract: In the general population, C-reactive protein (CRP) level increases in the presence of acute or chronic inflammation and infections. In patients with cirrhosis, the basal level is higher than in patients without cirrhosis, due to chronic hepatic and other inflammation, but when infection occurs the more severe the underlying liver dysfunction, the lower the increase in CRP. Therefore, the predictive power of CRP for infection and prognosis is weak in patients with decompensated/advanced cirrhosis and in the intensive care setting. However, higher CRP and also persistently elevated CRP levels can help identify patients with a higher short-term risk of mortality.

Risk factors for therapeutic ERCP-related complications: an analysis of 2,715 cases performed by a single endoscopist

Abstract: Background Endoscopic retrograde cholangiopancreatography (ERCP) is now the exclusive endoscopic therapeutic modality for biliary as well as pancreatic diseases. The aim of the present study was to investigate patient- and procedure-related risk factors for post-ERCP complications in a large-scale study of procedures performed by a single experienced endoscopist. Methods This is a retrospective cohort study which included a total of 2,715 therapeutic ERCPs enrolled in the final analysis. Potential important patient- and procedure-related risk factors for overall post-ERCP complications, pancreatitis and post-endoscopic sphincterotomy (ES) bleeding were investigated by univariate and multivariate analyses. Results Following the first therapeutic ERCP, 327 patients suffered complications; pancreatitis was observed in 132 (4.9%) patients, hemorrhage in 122 (4.5%) patients, cholangitis in 63 (2.3%) patients, perforation in 3 (0.11%) patients, and basket impaction in 7 (0.26%) patients. History of acute pancreatitis was more common in patients with post-ERCP complications (P<0.001). Female gender, young age (<40 years), periampullary diverticulum, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct and suprapapillary fistulotomy were not found to be risk factors for overall post-ERCP complications and postERCP pancreatitis (PEP). Multivariate analysis showed a history of acute pancreatitis, difficult cannulation, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first and second class pancreatic ductules and acinarization as independent risk factors for overall complications and PEP, whereas antiplatelet and anticoagulation drug use were not found to be independent risk factors for post-ES bleeding. Conclusions The results of this study demonstrate that the endoscopist’s experience reduces patient- and procedure-related risk factors for post-ERCP complications.

DNA methylation changes in inflammatory bowel disease.

Abstract: The cause of inflammatory bowel disease, encompassing Crohn’s disease and ulcerative colitis, remains a mystery but evidence is accumulating that complex interactions between the genetic background and the gut microbiota of the host and environmental factors associated with rapid industrialization and westernized life styles may underlie its pathogenesis. Recent epigenetic studies have suggested that interactions between environment and host DNA may play a leading role in the phenotypical expression of both diseases, explaining amongst others the differences in disease expression in monozygotic twins. DNA methylation is the most studied epigenetic modification and during the last decade its correlation to IBD pathogenesis has been well established. Genes from different molecular pathways have been studied but till now there is no standardized database of methylated genes in IBD. Thus, a thorough and in depth study of DNA methylation, its potential relation to IBD and its interaction with the available pharmaceutical armamentarium is of great interest.

The clinical significance of occult HBV infection

Abstract: The presence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg)-negative individuals is defined as occult HBV infection (OBI). OBI is related in some cases to infection with variant viruses (S-escape mutants) undetectable by HBsAg commercial kits. More frequently, however, it is due to infection with wild-type viruses that are strongly suppressed in their replication activity. OBI may be involved in different clinical contexts, including the transmission of the infection by blood transfusion or liver transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it may contribute to the development of cirrhosis and may have an important role in hepatocarcinogenesis.

Clinical course and prognosis in ulcerative colitis: results from population-based and observational studies

Abstract: The clinical course of ulcerative colitis (UC) may range from a quiescent course with prolonged periods of remission to fulminant disease requiring intensive medical treatment or surgery. Disease outcome is often determined by relapse rates, the development of colorectal cancer (CRC) and mortality rates. Early patient classification, identifying those with a high risk of developing complicated disease, is essential for choosing appropriate treatment. This paper reviews the clinical outcomes of UC patients as reported in population-based and observational studies representative of the whole patient population. Extensive colitis, a high level of systemic symptoms and young age at diagnosis are factors associated with a high risk of colectomy. Patients with distal disease who progress to extensive colitis seem to be a subgroup with an especially high risk of colectomy. Some prognostic factors of severe disease have been identified which could be used to optimize treatment and possibly reduce future complications. The overall risk of CRC and mortality was not significantly different from that of the background population. These results may have implications for follow-up strategies, especially regarding endoscopic surveillance of UC patients.

Therapeutic drug monitoring in inflammatory bowel disease

Abstract: Tumor necrosis factor (TNF)-α inhibitors and thiopurines are among the most important classes of medications utilized in the clinical management of Crohn's disease and ulcerative colitis. A significant proportion of patients loses response to these agents or develops adverse effects during the course of the treatment. Monitoring of drug levels and anti-drug antibodies (for TNF-α inhibitors) and metabolite levels (for thiopurines) can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients. This review summarizes the current knowledge on the clinical implications of therapeutic drug monitoring in inflammatory bowel disease patients treated with TNF-α inhibitors and thiopurines.

Morphological features of fluid collections on endoscopic ultrasound in acute necrotizing pancreatitis: do they change over time?

Abstract: Background There have been attempts to develop universally applicable nomenclature for pancreatic fluid collections (PFCs) in acute pancreatitis. But PFCs following acute necrotizing pancreatitis (ANP) has not been studied by sensitive imaging techniques like endoscopic ultrasound (EUS). The aim of the study was to prospectively study morphological structure of pancreatic fluid collections occurring after ANP by serial EUS. Methods Patients with ANP having PFC at ≥4 weeks of onset of symptoms seen at our center from October 2011 to November 2012 were prospectively followed up with EUS at 6 weeks, 3 months and 6 months respectively and the amount of solid content in the collection was quantified as percentage amount of echogenic material. The symptomatic patients undergoing EUS/percutaneous drainage also underwent EUS prior to drainage for assessment of solid content. Results Of the 54 patients enrolled, 7 patients were lost to follow up or refused EUS. Forty seven patients (34 males; mean age 36.7±11.6 years) were studied. Etiology of acute pancreatitis was alcohol (n=22), gallstones (n=10), idiopathic (10), gallstones+alcohol (n=3) and drug induced (n=2). Contrast enhanced computed tomography done after 3 days of onset of ANP had shown less than 30%, 30-50% and more than 50% necrosis in 6 (13%), 14 (30%) and 27 (57%) patients respectively. On EUS at 6 weeks, 41/47 (87%) patients had fluid collection with solid debris. Follow up EUS at 3 and 6 months revealed progressively decreasing solid content in PFCs. Conclusions All PFCs following ANP may not have solid necrotic content and over a period of time necrotic content tends to liquefy. This may have therapeutic implications. Keywords Endoscopic ultrasound, walled off pancreatic necrosis, acute pancreatitis, computed tomography Ann Gastroenterol 2014; 27 (3): 258-261

The hepatoprotective and hypolipidemic effects of Spirulina (Arthrospira platensis) supplementation in a Cretan population with non-alcoholic fatty liver disease: a prospective pilot study.

Abstract: Background A pilot study was conducted to determine the effects of Spirulina (Arthrospira platensis) on Cretan patients with non-alcoholic fatty liver disease (NAFLD). Spirulina is a filamentous cyanobacterium taken as a dietary supplement. Methods Fifteen adult Cretan outpatients (13 men), median age 48 (range: 29-62) years, with NAFLD were orally supplemented with 6 g of Spirulina (Greek production) per day for six months. Anthropometric characteristics (height, weight, waist circumference), systolic and diastolic blood pressure, complete blood count, biochemical assessments, homeostasis model assessment of insulin resistance (HOMA-IR) index, health-related quality of life and abdominal sonographic findings were recorded and measured, before and after Spirulina supplementation. Results At the end of the 6-month intervention period, the mean levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, triglycerides, low-density lipoproteincholesterol, total cholesterol, and the ratio of total cholesterol to high-density lipoprotein cholesterol were significantly decreased: 38.5%, 37.5%, 26.7%, 24.8%, 9.6%, 9.1%, and 13.5% respectively, whereas the mean levels of high-density lipoprotein-cholesterol and hemoglobin were significantly increased: 4.2% and 4.1% respectively. Spirulina supplementation resulted also in a significant reduction in weight and HOMA-IR index (8.1% and 19.6% respectively) and a significant improvement in healthrelated quality of life scale. No changes in sonographic findings were observed. Conclusion Spirulina supplementation at a high dosage of 6 g daily in NAFLD patients has strong and multiple beneficial metabolic effects and improves their health-related quality of life. Keywords Arthrospira, lipids, liver, NAFLD, spirulina, steatosis Ann Gastroenterol 2014; 27 (4): 387-394

The role of HBsAg levels in the current management of chronic HBV infection

Abstract: Chronic hepatitis B virus (HBV) infection can result in liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). However, the natural course of the disease is highly dynamic and not every patient requires therapy. The challenges for optimal management are who to treat, which therapeutic regimen to use, and when to begin or stop treatment. Constant monitoring is mandatory to predict the natural course and guide treatment decisions. Surrogate markers for baseline and on treatment decisions are needed. Besides HBV DNA, hepatitis B surface antigen levels also proved to be useful to help judge the natural course and guide treatment. High levels of HBsAg are suggestive of low fibrosis and immune tolerance in hepatitis B e antigen (HBeAg) positive patients; whereas low levels of HBsAg indicate a lower risk for HCC and inactive carrier state in HBeAg negative patients. Data also support the possible use of HBsAg levels as an on-treatment response marker. So far, the best evidence exists for treatment with interferon (IFN)-α where lack of HBsAg decline after 12 weeks is associated with non-response. Thus, stopping rules after 12 weeks therapy could be established for HBeAg positive as well as for HBeAg negative patients. However, the positive predictive value for achieving sustained response is still vague. The value of HBsAg monitoring is less clear during treatment with nucleos(t)ide analogues (NA) but it can be a useful marker for new concepts such as stopping NA or add-on IFN strategies. Currently, several studies are underway to validate HBsAg in these settings.

Beta-blockers in liver cirrhosis

Abstract: Since the original description of the effectiveness of β-blockers in lowering the portal pressure and therefore the risk of variceal bleeding, more than 500 articles in the English literature on the use of non selective β-blockers (NSBB) in cirrhosis have been published. The use of NSBB in pre-primary prophylaxis of variceal bleeding is currently not indicated. In primary prophylaxis, patients with high risk small varices or large/medium varices should receive primary prophylaxis either with NSBB or with endoscopic band ligation if there are contraindications to NSBB. For secondary prophylaxis the current recommendation is to receive a combination of NSBB and endoscopic variceal ligation. In addition to lowering portal pressure, NSBB can also reduce bacterial translocation, potentially exerting multiple beneficial effects which go beyond the reduction of bleeding risk. Carvedilol is a NSBB with intrinsic anti-α(1)-adrenergic activity, possibly more effective than propranolol in lowering portal hypertension. A potential harmful effect of propranolol in patients with cirrhosis with refractory ascites deserves further confirmation. NSBB remain the cornerstone of therapy in cirrhotic patients with portal hypertension.

Study design considerations for irritable bowel syndrome clinical trials.

Abstract: Clinical trials of therapies intended to alleviate symptoms of irritable bowel syndrome (IBS) are prevalent. However, the ideal study design remains elusive since there is no obvious pathophysiological target and no universally accepted endpoint to assess symptom improvement in IBS. The purpose of this paper is to identify and discuss the most problematic issues in the design of clinical trials intended to evaluate the effectiveness of treatments for IBS symptoms. Lack of standardized diagnostic criteria, symptom variability, heterogeneous subject characteristics, large placebo effects, lack of statistical power, inappropriate endpoint selection, and poorly selected study design are the most critical issues that may confound study outcomes in IBS clinical trials.

Helicobacter pylori infection in patients with liver cirrhosis: prevalence and association with portal hypertensive gastropathy

Abstract: Background The role of Helicobacter pylori (H. pylori) in the pathogenesis of portal hypertensive gastropathy (PHG) in cirrhotic patients is poorly defined. The aim of this study was toinvestigate the prevalence of H. pylori infection and its association with PHG in patients with liver cirrhosis. Methods Seroprevalence of H. pylori was tested in 70 cirrhotic patients with PHG (cases) and 70 cirrhotic patients without PHG (controls) using an anti-H. pylori IgG ELISA. All patients underwent upper gastrointestinal endoscopy to assess the severity of PHG and grade of varices. Results The presence of H. pylori was observed in 31 (44.3%) cirrhotic patients with PHG (cases) compared to 19 (27.1%) cirrhotic patients without PHG (controls). The risk estimate showed a significant association between H. pylori and PHG in cirrhotic patients (P=0.034, OR 2.134, 95% CI 1.052-4.327). Out of the 31 patients with PHG and H. pylori infection, 19 had severe PHG and 12 had mild PHG while 5 patients had severe PHG and 34 had mild PHG in the group of H. pylori negative patients. The difference was statistically significant (P<0.001, OR 10.767, 95% CI 3.293-35.205). Of the 70 patients with PHG, 24 had severe PHG and of these 18 (75%) were in Child C compared to 6 (25%) in Child B. Conclusion There is significant association between H. pylori infection and PHG in cirrhotic patients which is also related to severity of PHG. Thus, H. pylori needs to be eradicated in cirrhotic patients with PHG.

Cardiac dysfunction in cirrhotic portal hypertension with or without ascites.

Abstract: Background Alteration of cardiovascular functions in patients with liver cirrhosis has been described and it correlates with severity of hepatic failure. But cardiac functions by conventional 2-dimensional (2-D) echocardiography has limitations. The aim of the study was to evaluate cardiac systolic and diastolic functions in liver cirrhosis patients with or without ascites by tissue Doppler imaging and conventional 2-D- echocardiography. Methods A cross sectional case control study of sixty patients. Twenty subjects grouped as healthy controls, pre-ascitic cirrhosis and cirrhosis with ascites were enrolled. Cardiac evaluation was done by both conventional Doppler and tissue Doppler echocardiography. Results Cirrhosis with portal hypertension is associated with increased heart rate, ejection fraction and mean peak systolic velocity, while mean arterial pressure is decreased. All cardiac chamber dilation occurs and is mostly seen in the left atrium. Ratio of early diastolic annular velocity to peak early diastolic annular wave velocity (E/eʹ) was the most significant marker for diastolic dysfunction. E/eʹ ratio was 7.76±0.40, 12.55±1.73 and 11.4±1.19 in healthy controls, preascitic cirrhosis and ascitic cirrhosis respectively (P<0.0001). Overall Type I and II Left ventricular diastolic dysfunction was present in 70% cirrhotic patient with or without ascites, while there were no cases of Type III (Severe) diastolic dysfunction. Conclusion Left ventricular diastolic dysfunction is commonly associated with advancement of hepatic dysfunction while systolic function is maintained till advanced hepatic failure. Peak early diastolic wave velocity, deceleration time and E/e’ ratio for left ventricular diastolic dysfunction are accurately assessed by pulsed tissue Doppler imaging. Keywords Tissue Doppler imaging, peak systolic velocity, early diastolic velocity, late diastolic velocity, peak early diastolic wave velocity Ann Gastroenterol 2014; 27 (3): 244-249

Recent developments in the surgical management of perianal fistula for Crohn’s disease

Abstract: Perianal manifestations of Crohn’s disease (CD) are common and, of them, fi stulas are the most common. Perianal fi stulas can be extremely debilitating for patients and are oft en very challenging for clinicians to treat. CD perianal fi stulas usually require multidisciplinary and multimodality treatment, including both medical and surgical approaches. Th e majority of patients require multiple surgical interventions. CD patients with perianal fi stulas have a high rate of primary nonhealing, surgical morbidity, and high recurrence rates. Th is has led to constant eff orts to improve surgical management of this disease process.

Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome

Abstract: Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms “ion channels” “or” “receptors” “and” “visceral hypersensitivity” “or” “visceral nociception” “and” “irritable bowel syndrome”. Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models.

Normal values and reproducibility of the real-time index of vagal tone in healthy humans: a multi-center study.

Abstract: Background Th e parasympathetic nervous system has been implicated in the pathogenesis of a number of gastrointestinal disorders including irritable bowel syndrome. Within the fi eld, cardiometric parameters of parasympathetic/vagal tone are most commonly derived from time, or frequency, domain analysis of heart rate variability (HRV), yet it has limited temporal resolution. Cardiac vagal tone (CVT) is a non-invasive beat-to-beat measure of brainstem eff erent vagal activity that overcomes many of the temporal limitations of HRV parameters. However, its normal values and reproducibility in healthy subjects are not fully described. Th e aim of this study was to address these knowledge gaps. Methods 200 healthy subjects (106 males, median age 28 years, range 18-59 years) were evaluated across three study centers. Aft er attachment of CVT recording equipment, 20 min of data (resting/no stimulation) was acquired. 30 subjects, selected at random, were restudied aft er 1 year. Results Th e mean CVT was 9.5±4.16 linear vagal scale (LVS). Th us, the normal range (mean±2 standard deviations) for CVT based on this data was 1.9-17.8 LVS. CVT correlated negatively with heart rate (r=-0.6, P=0.001). CVT reproducibility over 1 year, as indexed by an intra-class correlational coeffi cient of 0.81 (95% confi dence interval 0.64-0.91), was good. Conclusions In healthy subjects, the normal range for CVT should be considered to be 1.9-17.8 LVS and is reproducible over 1 year. Future research utilizing CVT should refer to these values although further study is warranted in patient groups.

Low hygiene and exposure to infections may be associated with increased risk for ulcerative colitis in a North Indian population.

Abstract: Background Previous studies have attempted to link hygiene hypothesis with IBD. However most of these studies come from developed countries where the level of hygiene is high and universal. Very little data is available from developing countries. The present study explores the truth of hygiene hypotheses and other risk factors for ulcerative colitis (UC) in a North Indian population where the prevalence of UC has been increasing. Methods A total of 518 patients diagnosed with UC and 188 age-matched controls were included in the study. A structured questionnaire concerning socio-demographics and level of hygiene was completed by all participants. Logistic regression analysis was used to study the association between hygiene-related factors and the risk for UC. Odds ratios and 95% confidence intervals were estimated. Results There was a higher proportion of females (P<0.001), and a higher educational status (P=0.01) in UC patients compared with controls. A family history of IBD was present in 7.2% of cases and non-existent in controls. On multivariate analysis, after accounting for potential confounders, having a private bed (P<0.001), and having better toilet facilities [(RCA versus none, P=0.01; Flush toilet versus none, P=0.01), (RCA LATRINE as a toilet technology used in rural areas where no flush facility exists. It was developed under RCA project)] were inversely associated with risk for UC whereas owning a pet (P=0.01) and stressful events like a death in the family (P=0.01) were associated with greater risks for UC. Conclusion Our study does not provide definitive evidence to support hygiene hypothesis and rather suggests that the rising incidence of UC in North India may be attributable to inadequate sanitary measures or other as yet unidentified factors. Keywords Hygiene hypothesis, ulcerative colitis, infections Ann Gastroenterol 2014; 27 (3): 219-223

Gelatin tannate for treating acute gastroenteritis: a systematic review

Abstract: Gelatin tannate (GT) is a complex of tannic acid, which possesses astringent, antibacterial, and anti-inflammatory properties, and a protective gelatin. It is increasingly being marketed as an antidiarrheal drug. Our aim was to review data on the effectiveness of GT in treating acute gastroenteritis (AGE) in children and adults. The MEDLINE, EMBASE, and the Cochrane Library databases were searched in July 2013, with no language restrictions, for controlled clinical trials. Additional references were obtained from reviewed articles. Two trials met the inclusion criteria. In adults, one randomized controlled trial involving 40 subjects (mean age: 43±13 years) found that, compared with placebo, GT may be more effective at reducing some symptoms of AGE in the first 48 h after initiation of treatment. In children, one poor quality study (no randomization and no blinding) involving 211 children (mean age: 2.5±2.4 years) reported some beneficial effect of GT at 12 h after initiation of treatment. None of the studies evaluated the effect of GT on the primary outcome measures for this review such as stool output, duration of diarrhea, admission to hospital, duration of hospital stay, and (in children) weight gain after rehydration. Currently, there is no evidence to support the use of GT for treating AGE in children and only sparse evidence to support the use of GT in adults. Further well-designed trials, with sufficient power, adequate follow-up periods, and clinically relevant outcome measures, are needed. These include stool volume, duration of diarrhea, admission to hospital, duration of hospital stay, weight gain after rehydration, and adverse effects.

Capsule endoscopy in patients with cardiac pacemakers, implantable cardioverter defibrillators and left heart assist devices.

Abstract: According to the recommendations of the US Food and Drug Administration and manufacturers, capsule endoscopy should not be used in patients carrying implanted cardiac devices. For this review we considered studies indexed (until 30.06.2013) in Medline [keywords: capsule endoscopy, small bowel endoscopy, cardiac pacemaker, implantable cardioverter defibrillator, interference, left heart assist device], technical information from Given Imaging and one own publication (not listed in Medline). Several in vitro and in vivo studies included patients with implanted cardiac devices who underwent capsule endoscopy. No clinically relevant interference was noticed. Initial reports on interference with a simulating device were not reproduced. Furthermore technical data of PillCam (Given Imaging) demonstrate that the maximum transmission power is below the permitted limits for cardiac devices. Hence, impairment of cardiac pacemaker, defibrillator or left ventricular heart assist device function by capsule endoscopy is not expected. However, wireless telemetry can cause dysfunction of capsule endoscopy recording. Application of capsule endoscopy is feasible and safe in patients with implanted cardiac devices such as pacemakers, cardioverter defibrillators, and left heart assist devices. Development of new technologies warrants future re-evaluation.

Application of confocal laser endomicroscopy in the diagnosis and management of Barrett's esophagus.

Abstract: Confocal laser endomicroscopy is an advanced endoscopic imaging modality that can be used for the diagnosis of early mucosal dysplasia in various gastrointestinal conditions. It provides histology-like images at 1000-fold magnification. The technology offers potential advantages in the diagnosis of Barrett’s esophagus and early esophageal cancer due to the low yield of the current practice of surveillance endoscopy with biopsies. Confocal laser endomicroscopy has the potential to eliminate the need for biopsy, establish diagnosis and facilitate application of endoscopic therapy during the time of actual endoscopy. There are several studies that have demonstrated reasonable diagnostic accuracy in patients undergoing surveillance for Barrett’s esophagus from tertiary academic medical centers. However, the application of confocal laser endomicroscopy in routine clinical endoscopy is still in the process of refinement. Its role in the diagnosis and treatment of Barrett’s-associated dysplasia will continue to evolve with improvement in technology, criteria for diagnosis and experience among endoscopists in interpreting confocal imaging.

Analysis of NHANES 1999-2002 data reveals noteworthy association of alcohol consumption with obesity

Abstract: Background With the obesity pandemic sweeping the globe and alcohol use on the rise worldwide, there is growing interest in how the two might be linked epidemiologically. The aim of the study was to use data from the NHANES registry from 1999-2002 to analyze the association between obesity and alcohol use. Methods Multivariate logistic regression was used to assess the relationship between alcohol use and obesity. Risk was assessed separately for men and women. Results Of the 9,193 individuals (49% males), 26.8% of males and 33.6% of females were obese. About 17% of males and 12% of females were never drinkers (less than 12 drinks in their lifetime). After adjusting for age, race, marital status, highest level of education of the individual and spouse, country of origin, annual household income and duration of physical activity in the past 30 days, the odds of obesity were higher in never drinkers compared to ever drinkers in both men and women. Consumption of alcohol for more than 45 days, binge drinking (>5 drinks/day) for more than 90 days and being “ever binge drinker” were associated with significantly higher odds of obesity (in both genders) than those who drank for shorter duration or were “never binge drinkers”. Consumption of alcohol more than the recommended limit for moderate drinking (3 drinks/day in females and 4 drinks/day in males) was associated with increased (OR 1.074, 95%CI 1.072-1.076) and decreased (OR 0.970, 95%CI 0.968-0.972) obesity in females and males respectively.

Effectiveness of adalimumab for ambulatory ulcerative colitis patients after failure of infliximab treatment: a first "real-life" experience in primary gastroenterology centers in Italy.

Abstract: Background Adalimumab (ADA) is the key treatment for ulcerative colitis (UC) unresponsive or intolerant to standard treatments. Our aim was to assess the effi cacy and safety of ADA in treating ambulatory UC patients in primary gastroenterology centers. Methods Fift een patients (6 male, median age 29.9 years, range 22.8-39.9 years) were enrolled. All were previously treated with infl iximab (IFX). Clinical activity and endoscopic severity were scored according to the Crohn’s disease activity index (CDAI) score and Mayo subscore for endoscopy, respectively. Patients were clinically assessed at weeks 4, 8, and thereaft er at weeks 16, 24, 32, 40, 48, and 54. Colonoscopy was performed before starting treatment, at weeks 24 and 54. Th e co-primary endpoints were clinical remission at 24 and 54 weeks. Th e secondary endpoints included: 1) sustained clinical remission; 2) steroid-sparing eff ect; 3) mucosal healing; 4) need for colectomy. Induction dose of ADA was 160 mg at week 0, and then 80 mg at week 2, while ADA maintenance treatment was 40 mg every two weeks. Results Clinical remission was obtained in 11 (73.3%) and 15 (100%) patients at weeks 24 and 54 respectively. Ten patients (66.7%) were able to discontinue steroids and were under corticosteroidfree remission at week 54. No patients underwent to colectomy. Eight patients (53.33%) at week 24 and 9 patients (60%) at week 54 achieved complete mucosal healing (Mayo endoscopic score 0). Side eff ects were reported in 2 of 15 patients (13.3%); none of those patients stopped treatment. Conclusion ADA seems to be eff ective and safe in UC outpatients aff ected by UC, and previously treated with IFX.

Clinicopathological and treatment analysis of 13 extragastrointestinal stromal tumors of mesentery and retroperitoneum.

Abstract: Background Extragastrointestinal stromal tumors (EGISTs) are extremely rare mesenchymal tumors histologically and immunophenotypically similar to GI stromal tumors (GISTs). The aim of this study was to analyze the clinicopathological factors and treatment outcome in 13 patients with EGISTs treated at a tertiary care center. Methods Of 109 patients with GISTs treated at our center between April 2002 and December 2012, 13 patients with EGISTs were analyzed for clinicopathological factors and treatment outcome. Results Mean age was 45.8 (range 30-61) years, and females constituted 62% with a male:female ratio of 0.6:1. The most common tumor sites were mesentery in 10 patients and retroperitoneum in 3 patients. Mean tumor size was 11.7 (range 5-18) cm. Four (31%) patients were metastatic at presentation, the most common site of metastases being the liver in 3 (75%) patients. Lymph node enlargement was seen in 2 patients. Surgery was performed in 8 (62%) patients, 7 with localized disease, and 1 with metastatic disease. R0 resection was achieved in 3 (38%) patients. Five (71%) patients were considered as high-risk. Recurrences were seen in 3 patients (patient 3, 5 and 13) with localized disease after surgical resection, at 18, 7 and 137 months, respectively. At the last follow up, 7 patients were alive and 6 died of disease progression. The median overall survival was 34 (7-148) months. Conclusions EGISTs present at a younger age in the developing than in the developed countries. Females are more commonly affected than males. Lymph node metastases may be commonly present. Keywords Extrgastrointestinal stromal tumors, mesentery, retroperitoneum Ann Gastroenterol 2015; 28 (1): 105-108

Factors predicting early discharge and mortality in post-percutaneous endoscopic gastrostomy patients

Abstract: Background The aim of our study was to ascertain factors that favor early discharge and predict mortality in post-percutaneous endoscopic gastrostomy (PEG) patients. Methods Successive patients who underwent successful PEG placement during a 10-year period in a single New York City hospital were included in the study. Data was retrospectively extracted from hospital electronic medical records. Results Two hundred and eighty-four patients underwent successful PEG placement. Forty-six patients (16%) were discharged within 3 days of PEG placement (early discharge). Two hundred and thirty six patients (84%) remained in hospital from 4 to 244 days (median 13.5) after PEG insertion (late discharge). Twenty-six (9%) patients died in-house after PEG placement. A serum albumin level <2.2 g/dL (P=0.007) and presence of 2 or more co-morbidities (P=0.019) were predictors of late discharge. A dementia indication was twice as likely to result in an early discharge compared to a stroke indication (OR 2.39; 95% CI 1.07-5.36; P=0.033). Female sex, positive urine cultures and low serum albumin levels were independent predictors of in-house mortality. Conclusion Clinical and laboratory markers may predict post-PEG mortality as well as early patient discharge. Keywords Post-PEG mortality, co-morbidities Ann Gastroenterol 2014; 27 (1): 42-47