Showing papers in "BMC Gastroenterology in 2014"

Intestinal permeability – a new target for disease prevention and therapy

Abstract: Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms ‘intestinal barrier’ and ‘intestinal permeability’ are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by ‘intestinal permeability’. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and – more recently recognized – obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.

Over-expression of COX-2 mRNA in colorectal cancer

Abstract: Background Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data strongly vary and seem to depend on the methodology used.

Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany

Abstract: Background Despite strong recommendations for colorectal cancer (CRC) screening, participation rates are low. Understanding factors that affect screening choices is essential to developing future screening strategies. Therefore, this study assessed patient willingness to use non-invasive stool or blood based screening tests after refusing colonoscopy.

The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center.

Abstract: Background Celiac disease is a multiform, challenging condition characterized by extremely variable features. Our goal was to define clinical, serological and histopathological findings in a large cohort of celiacs diagnosed in a single referral center.

A new adult appendicitis score improves diagnostic accuracy of acute appendicitis - a prospective study

Abstract: Background The aim of the study was to construct a new scoring system for more accurate diagnostics of acute appendicitis. Applying the new score into clinical practice could reduce the need of potentially harmful diagnostic imaging.

Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics.

Abstract: The liver is the first line of defence against continuously occurring influx of microbial-derived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved. Relative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n = 13), non-cirrhotic alcoholics (n = 15), non-alcoholic controls (n = 14) and in 7 healthy male volunteers using real-time quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples. Relative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p = 0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p = 0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p = 0.004). Our results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis.

Characterization and prognosis of patients with hepatocellular carcinoma (HCC) in the non-cirrhotic liver

Abstract: HCC predominantly develops in the condition of chronic inflammation that has led to liver cirrhosis. A small proportion of patients with HCC is diagnosed in the non-cirrhotic liver (NCL). Data on patients with HCC in NCL in advanced stages are scarce. A retrospective analysis was performed comparing 93 patients with HCC in NCL to 571 patients with HCC in liver cirrhosis (LC) with respect to clinical and demographic characteristics. Also factors influencing survival in patients with HCC in NCL were analyzed. Patients with HCC in NCL were diagnosed at older age and in more advanced tumor stages than patients with LC. More than 25% of patients with HCC in NCL presented with extrahepatic metastases. Only a minority of patients with HCC in NCL lacked any sign of hepatic damage. Risk factors for LC and risk factors for NAFLD are present in the majority of patients with HCC in NCL. The BCLC classification corresponded with the survival of patients with HCC in NCL although the therapeutic options differ from those for patients with liver cirrhosis. It will be one of the major challenges in the future to awake awareness of carrying a risk of hepatic malignancies in patients with chronic liver diseases apart from liver cirrhosis, especially in NAFLD. Surveillance programs need to be implemented if these are cost-effective.

Overall survival in response to sorafenib versus radiotherapy in unresectable hepatocellular carcinoma with major portal vein tumor thrombosis: propensity score analysis

Abstract: This study investigated the survival benefits of sorafenib vs. radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch. Ninety-seven patients were retrospectively reviewed. Forty patients were enrolled by the Kanagawa Liver Study Group and received sorafenib, and 57 consecutive patients received RT in our hospital. Overall survival was compared between the two groups with PVTT by propensity score (PS) analysis. Factors associated with survival were evaluated by multivariate analysis. The median treatment period with sorafenib was 45 days, while the median total radiation dose was 50 Gy. The Child-Pugh class and the level of invasion into hepatic large vessels were significantly more advanced in the RT group than in the sorafenib group. Median survival did not differ significantly between the sorafenib group (4.3 months) and the RT group (5.9 months; P = 0.115). After PS matching (n = 28 per group), better survival was noted in the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months; P = 0.025). A Cox model showed that des-γ-carboxy prothrombin <1000 mAU/mL at enrollment and RT were significant independent predictors of survival in the PS model (P = 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P = 0.007, HR, 0.434; 95% CI, 0.235 to 0.779; respectively). RT is a better first-line therapy than sorafenib in patients who have advanced unresectable HCC with PVTT.

Long term follow-up and liver-related death rate in patients with non-alcoholic and alcoholic related fatty liver disease

Abstract: Few studies have compared the prognosis and liver-related mortality in patients with NAFLD (nonalcoholic fatty liver disease) and AFLD (alcoholic fatty liver disease). We aimed to investigate the etiology and liver-related mortality of patients with liver biopsy verified fatty liver disease in a population based setting. In this retrospective study, all patients who underwent a liver biopsy 1984–2009 at the National University Hospital of Iceland were identified through a computerized pathological database with the code for fatty liver. Only patients with NAFLD and AFLD were included and medical records reviewed. The patients were linked to the Hospital Discharge Register, the Causes of Death Registry and Centre for Addiction Medicine. A total of 151 had NAFLD and 94 AFLD with median survival of 24 years and 20 years, respectively (p = NS). A total of 10/151 (7%) patients developed cirrhosis in the NAFLD group and 19/94 (20%) in AFLD group (p = 0.03). The most common cause of death in the NAFLD group was cardiovascular disease (48%). Liver disease was the most common cause of death in the AFLD group (36%), whereas liver-related death occurred in 7% of the NAFLD group. The mean liver-related death rate among the general population during the study period was 0.1% of all deaths. There was a significantly worse survival for patients in the AFLD group compared to the NAFLD group after adjusting for gender, calendar year of diagnosis and age at diagnosis (HR 2.16, p = 0.009). The survival for patients with moderate to severe fibrosis was significantly worse than for patients with mild fibrosis after adjusting for gender, calendar year of diagnosis and age at diagnosis (HR 2.09, p = 0.01). Patients with fatty liver disease showed a markedly higher risk of developing liver-related death compared to the general population. The AFLD group had higher liver-related mortality and had a worse survival than the NAFLD group. Patients with more severe fibrosis at baseline showed a worse survival than patients with none or mild fibrosis at baseline.

Chronic gastritis in China: a national multi-center survey

Abstract: Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity

Abstract: Background Non-celiac gluten sensitivity is a syndrome characterized by gastrointestinal and extra-intestinal symptoms occurring in a few hours/days after gluten and/or other wheat protein ingestion and rapidly improving after exclusion of potential dietary triggers. There are no established laboratory markers for non-celiac gluten sensitivity, although a high prevalence of first generation anti-gliadin antibodies of IgG class has been reported in this condition. This study was designed to characterize the effect of the gluten-free diet on anti-gliadin antibodies of IgG class in patients with non-celiac gluten sensitivity.

NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease.

Abstract: Background Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver.

Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model

Abstract: Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model. The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor β1 (TGF-β1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays. According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P <0.01). The percentage of the collagen proportionate area decreased from 16.72 ± 5.51 to 5.06 ± 1.27 after BM-MSC treatment (P <0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 ± 13.19) compared to the untreated cirrhotic group (85.81 ± 17.62; P <0.01). BM-MSC administration significantly decreased TGF-β1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-β1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation. BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.

Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C

Abstract: The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-β1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC). Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-β1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes. Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak’s fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-β1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients. Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFβ1 and IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2. ClinicalTrials.gov identifier: NCT02161952 . Protocol Registration Date: 06/11/2014.

Deregulated expression of circadian clock genes in gastric cancer.

Abstract: Gastric cancer (GC), an aggressive malignant tumor of the alimentary tract, is a leading cause of cancer-related death. Circadian rhythm exhibits a 24-hour variation in physiological processes and behavior, such as hormone levels, metabolism, gene expression, sleep and wakefulness, and appetite. Disruption of circadian rhythm has been associated with various cancers, including chronic myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, endometrial carcinoma, and breast cancer. However, the expression of circadian clock genes in GC remains unexplored. In this study, the expression profiles of eight circadian clock genes (PER1, PER2, PER3, CRY1, CRY2, CKIϵ, CLOCK, and BMAL1) of cancerous and noncancerous tissues from 29 GC patients were investigated using real-time quantitative reverse-transcriptase polymerase chain reaction and validated through immunohistochemical analysis. We found that PER2 was significantly up-regulated in cancer tissues (p < 0.005). Up-regulated CRY1 expression was significantly correlated with more advanced stages (stage III and IV) (p < 0.05). Our results suggest deregulated expressions of circadian clock genes exist in GC and circadian rhythm disturbance may be associated with the development of GC.

Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children.

Abstract: Paneth cell metaplasia (PCM) is well described in adults but little is known about the distribution of colonic Paneth cells and the occurrence of PCM in a paediatric population. The aim of this study is to determine whether Paneth cell hyperplasia or metaplasia characteristically occurs in the colons of children with newly diagnosed idiopathic inflammatory bowel disease (IBD). We retrospectively reviewed colonic series from 28 new diagnoses of paediatric IBD at a tertiary referral centre, and from a further 14 children with IBD-like symptoms whose colonic biopsies and ancillary investigations were normal. Paneth cells were counted at 6 anatomical sites in the colon, and at each site acute and chronic inflammation were assessed semi-quantitatively and the presence or absence of crypt architectural distortion and eosinophilia was documented. In control, ulcerative colitis (UC) and Crohn’s disease (CD) groups there was a gradient of decreasing Paneth cell numbers from caecum to rectum. Paneth cells were not seen in the distal colon in the control group, but they were present there in 11 of 13 patients with ulcerative colitis and 14 of 15 with Crohn’s disease. Only patients with IBD showed Paneth cell hyperplasia, assessed as more than 10 Paneth cells per 10 well-oriented crypts at any site. There was a statistically significant increase in Paneth cells in the caecum, ascending, transverse and descending colon in UC and in the ascending, transverse, descending and sigmoid colon in CD compared with controls. There was no significant difference between UC and CD. There was no correlation between the site of PCM and acute or chronic inflammation, crypt distortion or eosinophilia. Paneth cells are found in the proximal but not the distal colon in otherwise normal paediatric colonic series. A high proportion of UC and CD patients show PCM in the distal colon. This is present early in the disease and does not correlate with histological features of chronicity.

The relationship between hepatic resistin overexpression and inflammation in patients with nonalcoholic steatohepatitis

Abstract: Background The relationship between resistin and non-alcoholic steatohepatitis (NASH) is not clear, some studies claimed that serum resistin levels were associated with neither the presence of NASH nor its severity, others declared that serum resistin was related with inflammation and fibrosis in NASH. Our animal study verified that the distribution of resistin in the liver is correlated with inflammation in NASH. However, there is no pertinent study in humans.

Risk factors for early and delayed post-operative bleeding after endoscopic submucosal dissection of gastric neoplasms, including patients with continued use of antithrombotic agents

Abstract: Endoscopic submucosal dissection (ESD) has become widely accepted as a standard treatment for gastric epithelial neoplasms. Antithrombotic agents are widely used to prevent thromboembolic disease. However, the feasibility of endoscopic procedures for patients using such agents has been rarely investigated. The aim of this study was to identify risk factors for post-operative bleeding after gastric ESD and to evaluate the relationship between the use of antithrombotic agents and post-operative bleeding. From June 2005 to March 2014, 413 patients with 425 gastric neoplasms were treated by ESD. The demographic and clinical parameters associated with post-operative bleeding were investigated. 83 patients receiving antithrombotic agents were separately assessed using various methods of administration during the ESD procedure. Post-operative bleeding that occurred within 5 days of ESD was defined as early post-operative bleeding, whereas subsequent bleeding was defined as delayed bleeding. The overall post-operative bleeding rate was 4.7%. In patients with continued low-dose aspirin (LDA), heparin replacement (HR), or continued LDA along with HR, post-operative bleeding rates were 9.5%, 23.8%, and 25.0%, respectively. On multivariate analysis, a specimen size of ≥40 mm was a risk factor for early post-operative bleeding [odds ratio (OR) 6.08, 95% CI: 1.74–21.27], and HR and chronic kidney disease (CKD) requiring hemodialysis were risk factors for delayed bleeding (OR 12.23, 95% CI: 2.63–56.77 and OR 28.35, 95% CI: 4.67–172.11, respectively). Continued LDA was not a risk factor for post-operative bleeding. Large specimen size is a risk factor for early post-operative bleeding, and HR and CKD requiring hemodialysis are risk factors for delayed bleeding. Patients with risk factors should be carefully watched, allowing for the timing of post-operative bleeding after ESD.

The serotonin transporter gene polymorphism (5-HTTLPR) and irritable bowel syndrome: a meta-analysis of 25 studies

Abstract: The results of previous studies assessing the association between the 5-HTTLPR polymorphism of serotonin transporter gene and irritable bowel syndrome (IBS) are inconsistent. The aim of this study was to clarify the association between the 5-HTTLPR mutation and the presence of IBS and its subtypes with a meta-analysis of 25 studies. A thorough search for case–control studies evaluating the association between the 5-HTTLPR polymorphism of serotonin transporter gene and the presence of IBS was carried out in four electronic databases. A meta-analysis was performed in accordance with the Cochrane Handbook for systemic reviews. A total of 25 articles with 3443 IBS cases and 3359 controls were included into our meta-analysis. No significant association was found between this polymorphism and IBS in all populations. Whereas the LL genotype was demonstrated to be a risk factor for constipation predominant IBS (IBS-C) development in the overall population (LL vs SS: OR = 1.570, 95% CI = 1.147-2.148, P = 0.005, Bon = 0.030; LL vs LS: OR = 1.658, 95% CI = 1.180-2.331, P = 0.004, Bon = 0.024; LL vs LS/SS: OR = 1.545, 95% CI = 1.187-2.012, P = 0.001, Bon = 0.006). In the analysis of different ethnicities, L allele and LL genotype were significantly associated with increased IBS-C risk in the East Asian population (L vs S: OR = 1.487, 95% CI = 1.139-1.941, P = 0.003, Bon = 0.018; LL vs SS: OR = 2.575, 95% CI = 1.741-3.808, P = 0.000, Bon = 0.000; LL vs LS: OR = 3.084, 95% CI = 2.017-4.715, P = 0.000, Bon = 0.000; LL vs LS/SS: OR = 2.759, 95% CI = 1.933-3.938, P = 0.000, Bon = 0.000), but not in the Caucasian population. Different from the conclusions of the earlier meta-analyses, the 5-HTTLPR mutation affects IBS-C but not IBS-D and IBS-M development and this effect only exists in the East Asian population but not other populations.

Study of Helicobacter pylori genotype status in cows, sheep, goats and human beings

Abstract: Helicobacter pylori is one of the most controversial bacteria in the world causing diverse gastrointestinal diseases. The transmission way of this bacterium still remains unknown. The possibility of zoonotic transmission of H. pylori has been suggested, but is not proven in nonprimate reservoirs. In the current survey, we investigate the presence of H. pylori in cow, sheep and goat stomach, determine the bacterium virulence factors and finally compare the human H. pylori virulence factors and animals in order to examine whether H. pylori might be transmitted from these animals to human beings. This cross- sectional study was performed on 800 gastric biopsy specimens of cows, sheep, goats and human beings. The PCR assays was performed to detection of H. pylori, vacA and cagA genes. The PCR products of Ruminant’s samples with positive H. pylori were subjected to DNA sequencing analysis. Statistical tests were applied for data analysis. Overall 6 (3%) cows, 32 (16%) sheep and 164 (82%) human beings specimens were confirmed to be H. pylori positive; however we were not able to detect this bacterium in all 200 goat samples. The vacA s1a/m1a was the predominant H. pylori genotype in all three kinds of studied population. There was 3.4–8.4% variability and 92.9-98.5% homology between sheep and human samples. Considering the high sequence homology among DNA of H. pylori isolated from sheep and human, our data suggest that sheep may act as a reservoir for H. pylori and in the some extent share the ancestral host for the bacteria with human.

Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis.

Abstract: Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. The analysis included 9 studies (4 cohort, 5 case–control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose–response relationship. Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC.

Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis

Abstract: Efforts to identify cell sources and approaches for cell therapy of liver diseases are ongoing, taking into consideration the limits recognized for adult liver tissue and for other forms of stem cells. In the present study, we described the first procedure of via hepatic artery transplantation of human fetal biliary tree stem cells in patients with advanced cirrhosis. The cells were immune-sorted from human fetal biliary tree by protocols in accordance with current good manufacturing practice (cGMP) and extensively characterized. Two patients with advanced liver cirrhosis (Child-Pugh C) have been submitted to the procedure and observed through a 12 months follow-up. The resulting procedure was found absolutely safe. Immuno-suppressants were not required, and the patients did not display any adverse effects correlated with cell transplantation or suggestive of immunological complications. From a clinical point of view, both patients showed biochemical and clinical improvement during the 6 month follow-up and the second patient maintained a stable improvement for 12 months. This report represents proof of the concept that the human fetal biliary tree stem cells are a suitable and large source for cell therapy of liver cirrhosis. The isolation procedure can be carried out under cGMP conditions and, finally, the infusion procedure is easy and safe for the patients. This represents the basis for forthcoming controlled clinical trials.

Dietary guideline adherence for gastroesophageal reflux disease

Abstract: Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disease, and the cost of health care and lost productivity due to GERD is extremely high. Recently described side effects of long-term acid suppression have increased the interest in nonpharmacologic methods for alleviating GERD symptoms. We aimed to examine whether GERD patients follow recommended dietary guidelines, and if adherence is associated with the severity and frequency of reflux symptoms. We conducted a population-based cross-sectional study within the Kaiser Permanente Northern California population, comparing 317 GERD patients to 182 asymptomatic population controls. All analyses adjusted for smoking and education. GERD patients, even those with moderate to severe symptoms or frequent symptoms, were as likely to consume tomato products and large portion meals as GERD-free controls and were even more likely to consume soft drinks and tea [odds ratio (OR) = 2.01 95% confidence interval (CI) 1.12-3.61; OR = 2.63 95% CI 1.24-5.59, respectively] and eat fried foods and high fat diet. The only reflux-triggering foods GERD patients were less likely to consume were citrus and alcohol [OR = 0.59; 95% CI: 0.35-0.97 for citrus; OR = 0.41 95% CI 0.19-0.87 for 1 + drink/day of alcohol]. The associations were similar when we excluded users of proton pump inhibitors. GERD patients consume many putative GERD causing foods as frequently or even more frequently than asymptomatic patients despite reporting symptoms. These findings suggest that, if dietary modification is effective in reducing GERD, substantial opportunities for nonpharmacologic interventions exist for many GERD patients.

The epidemiology and treatment of anal fissures in a population-based cohort

Abstract: Anal fissure (AF) is regarded as a common problem, but there are no published epidemiologic data, nor information on current treatment. The purpose of this study was to examine the incidence, associated comorbidities, and treatment of AF in a population-based cohort. We conducted a retrospective analysis of all persons who were enrolled in one large regional managed care system and treated for AF during calendar years 2005–2011. All persons aged 6 years or older who had a clinic, hospitalization, or surgical procedure associated with AF were identified from utilization data. To identify comorbidities associated with AF, each case was matched by age and gender to 3 controls. There were 1,243 AF cases, including 721 (58%) females and 522 (42%) males; 150 (12%) of the cases occurred in children aged 6–17 years. The overall annual incidence was 0.11% (1.1 cases per 1000 person-years), but ranged widely by age [0.05% in patients 6–17 years to 0.18% in patients 25–34 years]. The incidence also varied by sex, and was significantly higher among females 12–24 years, and among males 55–64 years (P < 0.001). Comorbidities associated with AF included chronic constipation (prevalence 14.2% vs 3.6%), hypothyroidism (14.7% vs 10.4%), obesity (13.0% vs 7.7%), and solid tumors without metastasis (5.2% vs 3.7%) (P < 0.001 for all comparisons). A total of 448 were dispensed a topical prescription medication, 31 had botulinum toxin injection, and only 13 had lateral internal sphincterotomy. AF is a common clinical problem, and the incidence varies substantially by age and sex. Constipation, obesity, and hypothyroidism are associated comorbidities. Most patients are prescribed topical treatments, although it appears that many prescriptions are never filled. Surgical interventions for AF including botulinum toxin and lateral internal sphincterotomy are uncommon.

Decreasing incidence of inflammatory bowel disease in Eastern Canada: a population database study

Abstract: Nova Scotia has one of the highest incidences of inflammatory bowel disease (IBD) in the world. We wished to determine trends of IBD over time. All Provincial residents have government provided health insurance and all interactions with the hospital, and physician billing systems, are captured on an administrative database. We used a validated measure to define incident cases of Crohn’s (CD), ulcerative colitis (UC) and undifferentiated IBD (IBDU). Incidence rates of these diseases for the years 1996–2009 were calculated. Over the study period, 7,153 new cases of IBD were observed of which 3,046 cases were categorized as CD (42.6%), 2,960 as UC (41.4%) and 1,147 as IBDU (16.0%). Annual age standardized incidence rates were very high but have declined for CD from 27.4 to 17.7/100,000 population and for UC from 21.4 to 16.7/100,000. The decline was seen in all age groups and both genders. The decrease was not explained by a small increase in IBDU. The incidence of CD and UC are decreasing in Nova Scotia. If replicated elsewhere this indicates a reversal after a long period of increasing occurrence of IBD. This has implications for both epidemiology and health planning.

Covered versus uncovered self-expandable metallic stents for palliation of malignant gastric outlet obstruction: a systematic review and meta-analysis.

Abstract: Self-expandable metallic stents (SEMSs) are widely used for palliation of malignant gastric outlet obstruction (GOO). There are two types of SEMS, covered and uncovered, each with its own advantages and disadvantages. We aimed to compare the efficacy and safety between uncovered and covered SEMSs in the palliation of malignant gastric outlet obstruction. Databases including PubMed, EMBASE, the Cochrane Library, the Science Citation Index and momentous meeting abstracts were searched and evaluated by two reviewers independently. Nine trials involving 849 patients were analyzed. Meta-analysis showed there was no significant difference in technical success rate (RR 1.0, 95% CI [0.98, 1.01]), clinical success rate (RR 1.04, 95% CI [0.98, 1.11]), post-stenting dysphagia score (WMD −0.01, 95% CI [−0.52, 0.50]), stent patency (WMD −0.31, 95% CI [−1.73, 1.11]), overall complications (RR 1.07, 95% CI [0.87, 1.32]) and reintervention rate (RR 1.30, 95% CI [0.92, 1.83]) between covered and uncovered SEMSs group. However, covered SEMSs were associated with higher migration rate (RR 3.48, 95% CI [2.16, 5.62], P < 0.00001) and lower obstruction rate (RR 0.42, 95% CI [0.24, 0.73], P = 0.002). In the palliative treatment of malignant gastric outlet obstruction, both covered and uncovered SEMSs are safely and effective. Covered stents can reduce the risk of restenosis, whereas uncovered stents are effective in decreasing stent migration.

Abdominal attacks and treatment in hereditary angioedema with C1-inhibitor deficiency

Abstract: Hereditary angioedema (HAE) is characterized by unpredictable attacks of debilitating subcutaneous and mucosal edema. Gastrointestinal attacks are painful, of sudden onset and often mistaken for acute abdomen leading to unnecessary surgery. The purpose of this study was to analyze symptom presentation of gastrointestinal angioedema in pediatric and adult HAE patients. Information collected during the clinical development of ecallantide for treatment of acute HAE attacks included affected anatomic location, accompanying symptoms, medical history, and pain assessments. Efficacy endpoints included Treatment Outcome Score (TOS, maximum score = 100; minimally important difference = 30), a point-in-time measure of treatment response, and time to treatment response. Forty-nine percent of 521 HAE attacks only involved abdominal symptoms. The most commonly reported abdominal symptoms were distension (77%), cramping (73%) and nausea (67%). The most common pain descriptors were tender, tiring-exhausting, aching, cramping and sickening. White blood cell counts were elevated (>10 × 109/L) in 23% of attacks (mean ± SD: 15.1 ± 11.27 × 109/L). A high proportion of patients reported a history of abdominal surgery, including appendectomy (23%), cholecystectomy (16.4%), and hysterectomy (8.2%). Mean TOS at 4 hours post ecallantide was 77±33 versus 29±65 for placebo. Median time to significant symptom resolution was 165 minutes (95% CI 136, 167) for ecallantide versus >4 hours (95% CI 161, >4 hours) for placebo. Anaphylactic reactions occurred in 6 of the 149 treated patients. HAE should be considered in the differential diagnosis of patients with recurrent discrete episodes of severe, unexplained crampy abdominal pain associated with nausea. The data used in the analysis were gathered across multiple clinical trials conducted during the clinical development program for ecallantide. All of the studies were conducted using Good Clinical Practices (GCP) and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. Each site that participated in the clinical trials obtained the appropriate IRB or Ethics Committee approval prior to enrolling any patients. All patients provided written informed consent prior to undergoing any study-related procedures. Pediatric patients provided written assent and their parents or guardians gave written informed consent. The following trials have been registered at http://www.clinicaltrials.gov : EDEMA2 (identifier NCT01826916 ); EDEMA3 (identifier NCT00262080 ); EDEMA4 (identifier NCT00457015 ); and DX-88/19 (identifier NCT00456508 ).

Effectiveness and safety of ferric carboxymaltose treatment in children and adolescents with inflammatory bowel disease and other gastrointestinal diseases

Abstract: The treatment of iron deficiency anemia in children with inflammatory bowel disease is a particular challenge and often insufficient. Absorption of orally given iron may be impaired by intestinal inflammation and treatment with oral iron may aggravate intestinal inflammation. This retrospective study is the first to describe the use of intravenous ferric carboxymaltose (FCM) in the pediatric setting. All subjects who had received at least one dose of FCM intravenously in the observation period were included in this analysis with data collected for up to 3 months post last FCM dose. In total, 72 children between 0 and 18 years with underlying gastrointestinal disorders had been treated for concomitant iron deficiency anemia. The majority of patients had Crohn’s disease (40.3%) or ulcerative colitis (30.5%). The total number of FCM administrations was 147, the mean number per patient was 2.0 and the mean cumulative dose 821 mg iron (median single dose: 500 mg; max. 1000 mg). Post administration of FCM, correction of iron deficiency anemia was observed with improved mean hemoglobin levels from 9.5 g/dL at baseline to 11.9 g/dL within 5–12 weeks. Decreases in white cell count, platelets and C-reactive protein were observed post FCM, potentially suggesting reduced inflammation with iron repletion. Three subjects reported mild adverse drug reactions related to FCM; two of these were considered to be potentially related to long duration of administration and to high volume of saline solution for dilution. As such, the method of administration was amended to have a maximum infusion time of 60 minutes and dilution with less than or equal to 100 mL saline solution. Overall FCM was well tolerated in this pediatric population and appeared to be effective in correcting iron deficiency anemia. We cannot exclude that the correction of iron deficiency anaemia is in some part due to the treatment of the underlying disease and not related to the iron supplementation only.

A retrospective study showing maintenance treatment options for paediatric CD in the first year following diagnosis after induction of remission with EEN: supplemental enteral nutrition is better than nothing!

Abstract: A limited body of research suggests that ongoing maintenance enteral nutrition (MEN) can be beneficial in maintaining disease remission in Crohn’s Disease (CD). We aimed to assess how achievable MEN is and whether it helps to prolong remission. Patients newly diagnosed with CD in 2010 and 2011 who commenced exclusive enteral nutrition (EEN) for 8 weeks were followed up for a year post diagnosis. All patients who took EEN were encouraged to continue MEN post EEN. Data on azathioprine use was also collected. Categorical variables were compared using chi–square/Fischer’s exact test. Medians were expressed along with complete data ranges. 59 patients (34 male, median age 11.07 years, range 2.5-16.33 years) were identified. 11/59 (18%) had a poor response to EEN and were switched to steroids. 48/59 patients completed 8 weeks EEN and achieved clinical remission/response. 46/48 patients received Modulen IBD®, 29/48 (60%) consumed EEN orally and 19/48 (40%) via NGT. 15/48 (31%) patients were able to continue MEN post EEN completion. MEN was consumed for a mean of 10.8 months (range 4–14 months). 14/15 patients drank MEN and 1/15 had MEN via NGT. Remission rates at 1 year in patients continuing MEN were 60% (9/15) compared to15% (2/13) in patients taking no treatment (p = 0.001) and 65% (13/20) in patients taking azathioprine (p = 0.14). A sub group of patients can continue MEN as a maintenance treatment and this seems a useful strategy, especially in those who are not commencing azathioprine.

Initial presentations and final outcomes of primary pyogenic liver abscess: a cross-sectional study.

Abstract: Although pyogenic liver abscess (PPLA) fatalities are decreasing owing to early diagnosis and effective treatments, PPLA-associated complications still exist. The purpose of this study was to analyze the characteristic features of initial presentations and final outcomes of PPLA caused by different pathogens. This retrospective study collected and analyzed information regarding initial presentations and final outcomes in patients diagnosed with PPLA at admitted at Changhua Christian Hospital from January 1 to December 31, 2010. During the study period, we analyzed the records of a total of 134 patients with documented PPLA. There were no significant causative pathogen-related differences in symptoms at initial presentation. Compared with the survivor group, patients in the mortality group were characterized by male gender (p < 0.001), malignancy (p < 0.001), respiratory distress (p =0.007), low blood pressure (p = 0.024), jaundice (p = < 0.001), rupture of liver abscess (p < 0.001), endophthalmitis (p = 0.003), and multiple organ failure (p < 0.001). No patients received liver transplantation or were diagnosed with HIV during the study period. According to univariate logistic regression analysis, gender (OR = 1.185, 95% CI: 0.284–11.130, p = 0.006), malignancy (OR = 2.067, 95% CI: 1.174–13.130, p = 0.004), respiratory distress (OR = 1.667, 95% CI: 1.164–14.210, p = 0.006), low blood pressure (OR = 2.167, 95% CI: 2.104–13.150, p = 0.003), jaundice (OR = 1.9, 95% CI: 1.246–3.297, p = 0.008), rupture of liver abscess (OR = 5.167, 95% CI: 2.194–23.150, p = 0.003), endophthalmitis (OR = 2.167, 95% CI: 1.234–13.140, p = 0.005), and multiple organ failure (OR = 3.067, 95% CI: 1.184–15.150, p = 0.001) differed significantly between the mortality and survivor groups. Although the initial presentations of PPLA caused by different pathogens were similar, there were significant differences in mortality in cases involving: (1) male patients, (2) malignancy, (3) initial respiratory distress, (4) initial low blood pressure, (5) jaundice, (6) rupture of liver abscess, (7) endophthalmitis, , and (8) multiple organ failure. We strongly recommend using a severity score of the disease to determine the risk of mortality for each patient with PPLA. In order to prevent complications and reduce mortality, more attention must be paid to high-risk PPLA patients.