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1.  Colorectal cancer screening: Why immunochemical fecal occult blood tests may be the best option 
BMC Gastroenterology  2012;12:183.
There are many test options available for colorectal cancer screening. The choice of test relates to the objectives of those offering or considering screening.
While all screening programs aim to detect disease early in order to improve the length and/or quality of life for the individual, some organizations and individuals prefer screening tests that offer the opportunity for cancer prevention. Others favor maximizing participation or the opportunity for shared decision-making, including discussion of information on test quality and availability. We propose three additional objectives for screening: minimizing harms, optimizing economic efficiency and maximizing equity of access to screening.
Applying these objectives to colorectal cancer screening, we advocate the use of immunochemical FOBTs as the preferred screening strategy, as it satisfies all three of these important objectives.
PMCID: PMC3548714  PMID: 23272939
Screening objectives; Colorectal cancer; Fecal occult blood testing; Harm minimization; Equity; Economic efficiency; Prevention; Participation
2.  Additional corpus biopsy enhances the detection of Helicobacter pylori infection in a background of gastritis with atrophy 
BMC Gastroenterology  2012;12:182.
The best sites for biopsy-based tests to evaluate H. pylori infection in gastritis with atrophy are not well known. This study aimed to evaluate the site and sensitivity of biopsy-based tests in terms of degree of gastritis with atrophy.
One hundred and sixty-four (164) uninvestigated dyspepsia patients were enrolled. Biopsy-based tests (i.e., culture, histology Giemsa stain and rapid urease test) and non-invasive tests (anti-H. pylori IgG) were performed. The gold standard of H. pylori infection was defined according to previous criteria. The sensitivity, specificity, positive predictive rate and negative predictive rate of biopsy-based tests at the gastric antrum and body were calculated in terms of degree of gastritis with atrophy.
The prevalence rate of H. pylori infection in the 164 patients was 63.4%. Gastritis with atrophy was significantly higher at the antrum than at the body (76% vs. 31%; p<0.001). The sensitivity of biopsy-based test decreased when the degree of gastritis with atrophy increased regardless of biopsy site (for normal, mild, moderate, and severe gastritis with atrophy, the sensitivity of histology Giemsa stain was 100%, 100%, 88%, and 66%, respectively, and 100%, 97%, 91%, and 66%, respectively, for rapid urease test). In moderate to severe antrum or body gastritis with atrophy, additional corpus biopsy resulted in increased sensitivity to 16.67% compare to single antrum biopsy.
In moderate to severe gastritis with atrophy, biopsy-based test should include the corpus for avoiding false negative results.
PMCID: PMC3573986  PMID: 23272897
Gastritis with atrophy; Biopsy-based test; Biopsy site; Helicobacter pylori
3.  Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett’s esophagus 
BMC Gastroenterology  2012;12:181.
Recent advances in the management of Barrett’s Esophagus (BE) have placed greater emphasis on accurate diagnosis of BE as well as better prediction of risk for progression to esophageal adenocarcinoma (EAC). Histological evaluation of BE is particularly challenging with significant inter-observer variability. We explored the presence and extent of genomic instability in BE biopsy specimens as a means to add supplementary information to the histological classification and clinical decision-making related to early disease.
We reviewed histology slides from 271 patients known to have BE. Using histological features as a guide, we microdissected target cell populations with various histological classifications of BE (intestinal metaplasia, “indefinite for dysplasia”, low grade dysplasia, or high grade dysplasia). DNA was extracted from microdissected targets and analyzed for loss of heterozygosity (LOH) using a panel of 16 LOH mutational markers associated with tumor suppressor genes at chromosomal loci 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, 22q. The presence or absence of mutations and the clonality of each mutation were determined for each marker.
The presence and clonal expansion of LOH mutations was formulated into mutational load (ML) for each microdissected target analyzed. ML correlated with the histological classification of microdissected targets, with increasingly severe histology having higher ML. Three levels of mutation load (no ML, low ML, and high ML) were defined based on the population of microdissected targets histologically classified as intestinal metaplasia. All microdissected targets with dysplasia had mutations, with a high ML consistently present in high grade dysplasia targets. Microdissected targets histologically classified as intestinal metaplasia or “indefinite for dysplasia” spanned a range of no, low, and high ML.
The results of this study reinforce the association of genomic instability with disease progression in BE. The presence and extent (clonality) of genomic instability, as assessed by mutational load, may assist histology in defining early stages of BE that are potentially at greater risk for disease progression. Assessment of mutational load using our panel of LOH mutational markers may be a useful adjunct to microscopic inspection of biopsy specimens, and thereby, improve patient management.
PMCID: PMC3553041  PMID: 23270334
Barrett’s esophagus; Intestinal metaplasia; Indefinite for dysplasia; Low grade dysplasia; High grade dysplasia; Allelic imbalance; Loss of heterozygosity; Clonal expansion; Tumor suppressor gene mutation; Genomic instability
4.  High prevalence of celiac disease among Saudi children with type 1 diabetes: a prospective cross-sectional study 
BMC Gastroenterology  2012;12:180.
There is lack of data on prevalence of celiac disease (CD) in children with type 1 diabetes (T1D) in Arabs in the Middle East. The present investigation aims to study the prevalence rate and clinical characteristics of CD among Saudi children with T1D using a combination of the most sensitive and specific screening serologic tests (anti- tissue transglutaminase antibodies IgA [anti-TTG] and ednomyseal antibodies [EMA]) and to determine the lower cut-off value of anti- anti-TTG level that best predicts CD in children with T1D.
Children with T1D following in diabetic clinic have been prospectively screened for presence of CD, over a two-year period (2008–2010), by doing anti-TTG, EMA, and total IgA. Children with positive anti-TTG titres (>50 U/ml) and/or EMA and children with persistently low positive anti-TTG titres (two readings 20–50 U/ml; within 6 months intervals) had upper endoscopy and 6 duodenal biopsies.
One hundred and six children with T1D have been screened for CD: age ranged between 8 months to 15.5 years (62 females). Nineteen children had positive anti-TTG and/or EMA, however only 12 children had biopsy proven CD (11.3%). Five of 12 had gastrointestinal symptoms (42%). Children with T1D and CD had significantly lower serum iron than children with T1D alone (8.5 μgm/L Vs 12.5 μgm/L; P = 0.014). The sensitivity and specificity of anti-TTG were 91.6% and 93.6%, with a positive and negative predictive value of 64.7% and 98.8%, respectively. Receiver operated characteristics analysis for the best cut-off value of anti-TTG level for diagnosis of CD was 63 units (sensitivity 100% and specificity 98.8%).
CD is highly prevalent among Saudi children with T1D. Anti-TTG titres more than 3 times the upper limit of normal has very high sensitivity and specificity for diagnosis of CD in T1D children.
PMCID: PMC3543703  PMID: 23259699
Celiac disease; Type 1 diabetes; Anti-tissue transglutaminase; Ednomyseal antibody; Saudi Arabia
5.  Effects of crystalloids and colloids on liver and intestine microcirculation and function in cecal ligation and puncture induced septic rodents 
BMC Gastroenterology  2012;12:179.
Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and intestine injury and microcirculation in septic rodents.
Sepsis was induced by cecal ligation and puncture (CLP) in 77 male rats. Animals were treated with different crystalloids (NaCl 0.9% (NaCl), Ringer’s acetate (RA)) or colloids (Gelafundin 4% (Gel), 6% HES 130/0.4 (HES)). After 24 h animals were re-anesthetized and intestinal (n = 6/group) and liver microcirculation (n = 6/group) were obtained using intravital microscopy, as well as macrohemodynamic parameters were measured. Blood assays and organs were harvested to determine organ function and injury.
HES improved liver microcirculation, cardiac index and DO2-I, but significantly increased IL-1β, IL-6 and TNF-α levels and resulted in a mortality rate of 33%. Gel infused animals revealed significant reduction of liver and intestine microcirculation with severe side effects on coagulation (significantly increased PTT and INR, decreased haemoglobin and platelet count). Furthermore Gel showed severe hypoglycemia, acidosis and significantly increased ALT and IL-6 with a lethality of 29%. RA exhibited no derangements in liver microcirculation when compared to sham and HES. RA showed no intestinal microcirculation disturbance compared to sham, but significantly improved the number of intestinal capillaries with flow compared to HES. All RA treated animals survided and showed no severe side effects on coagulation, liver, macrohemodynamic or metabolic state.
Gelatine 4% revealed devastated hepatic and intestinal microcirculation and severe side effects in CLP induced septic rats, whereas the balanced crystalloid solution showed stabilization of macro- and microhemodynamics with improved survival. HES improved liver microcirculation, but exhibited significantly increased pro-inflammatory cytokine levels. Crystalloid infusion revealed best results in mortality and microcirculation, when compared with colloid infusion.
PMCID: PMC3547783  PMID: 23245375
Sepsis; Microcirculation; Colloids; HES; Crystalloids
6.  Efficacy of telbivudine in Taiwanese chronic hepatitis B patients compared with GLOBE extension study and predicting treatment outcome by HBV DNA kinetics at Week 24 
BMC Gastroenterology  2012;12:178.
The aims of this study were to compare results from a Taiwanese sub-study of the GLOBE 2303 telbivudine study and evaluate the HBV DNA kinetics.
Forty-one Taiwanese patients were treated for an additional 2 years with telbivudine. Efficacy endpoints were the same as the GLOBE study. The correlations of reductions in HBV DNA levels at Week 24 were evaluated.
All 7 HBeAg-positive patients with undetectable HBV DNA levels at Week 24 sustained this response at Year 4 with rates of ALT normalization 71%, HBeAg seroconversion 57%, and cumulative resistance 0%. Out of 16 HBeAg-negative patients with undetectable HBV DNA levels at Week 24, 11 (78%) sustained this response at Year 4 with rates of ALT normalization 83% and cumulative resistance 8.7%. There were significant correlations between reductions of DNA of ≥5 log10 copies/mL at Week 24 with maintained PCR negativity at Years 2–4 and a lack of resistance at Year 2.
Long-term telbivudine efficacy in Taiwanese patients was comparable to the GLOBE 2303 study. A reduction in HBV DNA levels by ≥5 log10 copies/mL at Week 24 represented the optimal cut-off point, which may predict favourable outcomes in patients with high baseline HBV DNA levels.
Trial registration Identifier: NCT00142298 (
PMCID: PMC3563525  PMID: 23234302
Chronic hepatitis B; HBV DNA kinetics; Roadmap concept
7.  Risk of esophagus cancer in diabetes mellitus: a population-based case-control study in Taiwan 
BMC Gastroenterology  2012;12:177.
Diabetes mellitus (DM) has been associated with the cancer risk. This study investigated relationship between DM and esophageal cancer using Taiwan’s insurance data.
We identified 549 patients with esophageal cancer newly diagnosed in 2000-2009 and randomly selected 2196 controls without any cancer, frequency matched by sex, age and diagnosis year of cases. Logistic regression model estimated odds ratios (ORs) and 95% confidence intervals (CI) of esophageal cancer associated with DM, sex, age. co-morbidities and medications.
Cases were more prevalent than controls for alcoholism and esophageal disorders and using nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 inhibitors but not DM. Esophageal cancer had no association with DM (OR 0.99, 95% CI 0.71-1.37), but significantly associated with alcoholism (OR 14.1, 95% CI 7.87-25.4), esophageal ulcer (OR 10.1, 95% CI 5.70-17.9), esophageal reflux (OR 3.47, 95% CI 2.14-5.26) and uses of NSAIDs (OR 2.73, 95% CI 1.80-4.13). An elevated risk of esophageal cancer appeared in DM patients taking insulin (OR 2.57, 95% CI 1.08-6.15) or sulfonyurea (OR 3.80, 95% CI 1.16-12.5).
Patients with DM are not at higher risk for esophagus cancer. However, esophageal disorders and anti-diabetic drugs are associated with the risk of the disease.
PMCID: PMC3531311  PMID: 23234272
Case-control study; Diabetes; Esophagus cancer; Insulin
8.  Small intestinal transit in patients with liver cirrhosis and portal hypertension: a descriptive study 
BMC Gastroenterology  2012;12:176.
Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers.
We included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C) and portal hypertension (11 males, median age 54 years (range 38–73), median hepatic venous pressure gradient 18 mmHg (range 12–37)), and 18 healthy controls (8 males, median age 58 years (range 34–64)). The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs.
The velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m)/hour, range 0.82–2.68) than in the healthy controls (median 1.00 m/hour, range 0.46–1.88) (p = 0.03). Likewise, the magnet travelled significantly longer in both fast (p = 0.04) and slow movements (p = 0.05) in the patient group. There was no significant difference in either gastric emptying time—23 minutes (range 5–131) in patients and 29 minutes (range 10.5–182) in healthy controls (p = 0.43)—or total gastrointestinal transit time—1.6 days (range 0.5–2.9) in patients and 2.0 days (range 1.0–3.9) in healthy controls (p = 0.33). No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine.
Patients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies.
PMCID: PMC3520867  PMID: 23216853
Liver cirrhosis; Portal hypertension; Gastrointestinal motility; Small intestinal transit time; Colonic transit time
9.  Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn’s disease 
BMC Gastroenterology  2012;12:175.
Patients with Crohn’s disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD.
Twenty-six patients with inactive Crohn’s disease, as defined by a Crohn’s Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores ≥ 6 were considered to have dyspepsia. The control group was composed by 19 age- and sex-matched healthy volunteers.
Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery.
Delayed gastric emptying in inactive Crohn’s disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.
PMCID: PMC3537636  PMID: 23216812
Dyspeptic; Gastric emptying; Crohn
10.  Percutaneous ultrasonographically guided liver punctures: an analysis of 1961 patients over a period of ten years 
BMC Gastroenterology  2012;12:173.
Ultrasonographically guided punctures of the liver represent a decisive tool in the diagnosis of many diseases of the liver. Objective of the study was to determine the extent to which the complication rate for ultrasonographically guided punctures of the liver is affected by less comprehensively studied risk factors.
A total of 2,229 liver biopsies were performed in 1,961 patients (55.5% males; 44.5% females). We recorded actual complications and assessed the following risk factors: needle gauge, puncture technique, examiner experience, coagulation status, puncture target (focal lesion versus parenchyma), lesion size, patient sex and age.
he rate of complications stood at 1.2% (n = 27), of which 0.5% (n = 12) were major and 0.7% (n = 15) minor complications. A significant increase in complications involving bleeding was observed with larger-gauge needles compared with smaller-gauge needles and for cutting biopsy punctures compared with aspiration biopsies (Menghini technique). In the bivariate analysis complications were 2.7 times more frequent in procedures performed by experienced examiners compared with those with comparatively less experience. Lower values for Quick’s test and higher partial thromboplastin times were associated with a higher rate of bleeding. Neither the puncture target, lesion size or patient sex exerted any measurable influence on the puncture risk. Advanced patient age was associated with a higher rate of complications involving bleeding.
Our study helps to establish the importance of potential and less comprehensively studied risk factors and may contribute to further reduction in complications rates in routine clinical practice.
PMCID: PMC3552862  PMID: 23216751
Liver; Biopsy; Ultrasonography; Complications; Risk factors
11.  Systemic lupus erythematosus complicated by Crohn’s disease: a case report and literature review 
BMC Gastroenterology  2012;12:174.
Although patients with systemic lupus erythematosus (SLE) may experience various gastrointestinal disorders, SLE and Crohn’s disease (CD) rarely coexist. The diseases may have gastrointestinal (GI) manifestations, laboratory results, and radiographic findings that appear similar and consequently differentiating between GI involvement in CD and in SLE may be difficult. We present the case of a patient with SLE and CD who developed continuous GI bleeding and diarrhea that was initially treated as SLE-related colitis to little effect.
Case presentation
A 55-year-old Japanese woman with systemic lupus erythematosus (SLE) developed continuous gastrointestinal bleeding and diarrhea since the patient was aged 30 years that was initially treated as SLE-related colitis. Although a longitudinal ulcer and aphthous ulcers in the colon were observed every examination, biopsy showed only mild inflammation and revealed neither granuloma nor crypt abscess. The patient underwent surgery for anal fistulas twice at 50 and 54 years of age and her symptoms were atypical of lupus enteritis. Colonoscopy was performed again when the patient was 55 years of age because we suspected she had some type of inflammatory bowel disease (IBD). Cobblestone-like inflammatory polyps and many longitudinal ulcers were detected between the descending colon and the cecum. Macroscopic examination strongly suggested CD. Histopathological examination revealed non-caseating granuloma and no evidence of vasculitis, consistent with CD. Introduction of infliximab dramatically relieved the patient’s melena and abdominal symptoms.
Diagnostic criteria for CD and SLE overlap, making them difficult to diagnose correctly. It is important to consider CD for patients who have SLE with gastrointestinal manifestations. The pathology of lupus enteritis should be clarified through the accumulation of cases of SLE combined with CD.
PMCID: PMC3573972  PMID: 23216789
Systemic lupus erythematosus (SLE); Crohn’s disease (CD); Longitudinal ulcer; Aphthous ulcers; Cobblestone-like inflammatory polyps; Non-caseating granuloma; Vasculitis; Infliximab
12.  Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo 
BMC Gastroenterology  2012;12:172.
Induced regulatory T (iTreg) lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg) cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore new techniques to generate iTreg cells and to determine their physiological relevance.
Using phorbol myristate acetate (PMA)/ionomycin and anti-CD3 activation of CD4+CD25- cells we generated in vitro functional CD4+CD25+ iTreg (TregPMA) cells. Functionality of the generated TregPMA cells was tested in vivo in a mouse model of inflammatory bowel disease (IBD) - CD45RB transfer colitis model.
TregPMA cells expressed regulatory markers and proved to ameliorate the disease phenotype in murine CD45RB transfer colitis model. The body weight loss and disease activity scores for TregPMA treated mice were reduced when compared to diseased control group. Histological assessment of colon sections confirmed amelioration of the disease phenotype. Additionally, cytokine analysis showed decreased levels of proinflammatory colonic and plasma IL-6, colonic IL-1 β and higher levels of colonic IL-17 when compared to diseased control group.
This study identifies a new method to generate in vitro iTreg cells (TregPMA cells) which physiological efficacy has been demonstrated in vivo.
PMCID: PMC3536706  PMID: 23198878
IBD; CD45RB transfer; Treg; PMA/ionomycin
13.  The Zelnorm epidemiologic study (ZEST): a cohort study evaluating incidence of abdominal and pelvic surgery related to tegaserod treatment 
BMC Gastroenterology  2012;12:171.
Pre-marketing clinical studies of tegaserod suggested an increased risk of abdominal surgery, particularly cholecystectomy. We sought to quantify the association between tegaserod use and the occurrence of abdominal or pelvic surgery, including cholecystectomy.
This cohort study was conducted within an insured population. Tegaserod initiators and similar persons who did not initiate tegaserod were followed for up to six months for the occurrence of abdominal or pelvic surgery. Surgical procedures were identified from health insurance claims validated by review of medical records. The incidence of confirmed outcomes was compared using both as-matched and as-treated analyses.
Among 2,762 tegaserod initiators, there were 94 abdominal or pelvic surgeries (36 gallbladder): among 2,762 comparators there were 134 abdominal or pelvic surgeries (37 gallbladder) (hazard ratio HR] = 0.70, 95% confidence interval [C.I.] = 0.54-0.91 overall, HR = 0.98, 95% C.I. = 0.62-1.55 for gallbladder). Current tegaserod exposure compared to nonexposure was associated with a rate ratio [RR] of 0.68 (95% C.I. = 0.48-0.95) overall, while the RR was 0.99 (95% C.I. = 0.56-1.77) for gallbladder surgery.
In this study, tegaserod use was not found to increase the risk of abdominal or pelvic surgery nor the specific subset of gallbladder surgery.
PMCID: PMC3536557  PMID: 23198861
Abdominal surgery; Tegaserod; Cohort study
14.  Role of vitamin K2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: A meta-analysis of randomized controlled trials 
BMC Gastroenterology  2012;12:170.
Hepatocellular cancer is notorious for recurrence even after curative therapy. High recurrence determines the long term prognosis of the patients. Vitamin K2 has been tested in trials for its effect on prevention of recurrence and improving survival. The results are inconclusive from individual trials and in our knowledge no systematic review which entirely focuses on Vitamin K2 as a chemo preventive agent is available to date. This review is an attempt to pool all the existing trials together and update the existing knowledge on the topic.
Medline, Embase and Cochrane Register of Controlled trials were searched for randomized controlled trials where vitamin K2 or its analogues, in any dosage were compared to placebo or No vitamin K2, for participants of any age or sex. Reference lists and abstracts of conference proceedings were searched by hand. Additional papers were identified by a manual search of the references from the key articles. Attempt was made to contact the authors of primary studies for missing data and with the experts in the field.
Trials were assessed for inclusion by two independent reviewers. Primary outcomes were recurrence rates and survival rates. There were no secondary outcomes. Data was synthesized using a random effects model and results presented as relative risk with 95% Confidence Intervals.
For recurrence of hepatocellular cancer after hepatic resection or local ablative therapy, compared with controls, participants receiving Vitamin K2, pooled relative risks for hepatocellular cancer were 0.60; 95% CI: 0.28–1.28, p = 0.64) at 1 yr 0.66; 95% CI: 0.47–0.91), p = 0.01) at 2 yr; 0.71; 95% CI: 0.58–0.85, p = 0.004) at 3 yr respectively. The results were combined using the random analysis model.
Five RCTs evaluated the preventive efficacy of menatetrenone on HCC recurrence after hepatic resection or local ablative therapy. The meta-analysis of all five studies, failed to confirm significantly better tumor recurrence- free survival at 1 year. Improved tumor recurrence at 2nd and 3rd year may be just due to insufficient data. There was no beneficial effect on the overall survival. However, to confirm the beneficial effect or lack of it, large, higher quality randomized controlled trials are still required.
PMCID: PMC3574058  PMID: 23191943
15.  Marginal turbid band and light blue crest, signs observed in magnifying narrow-band imaging endoscopy, are indicative of gastric intestinal metaplasia 
BMC Gastroenterology  2012;12:169.
Gastric intestinal metaplasia (IM) usually appears in flat mucosa and shows few morphologic changes, making diagnosis using conventional endoscopy unreliable. Magnifying narrow-band imaging (NBI) endoscopy enables evaluation of detailed morphological features that correspond with the underlying histology. The aim of this study was to investigate and clarify the diagnostic efficacy of magnifying NBI endoscopic findings for the prediction and diagnosis of IM.
Forty-seven patients were prospectively enrolled, and magnifying NBI examinations were performed in the lesser curvature of the midbody and the greater curvature of the upper body. The marginal turbid band (MTB) was defined as an enclosing white turbid band on the epithelial surface/gyri; light blue crest (LBC), as a fine, blue-white line on the crest of the epithelial surface/gyri. Immediately after observation under magnifying endoscopy, biopsy specimens were obtained from the evaluated areas.
The degree of IM significantly increased with increasing MTB/LBC positivity (MTB-/LBC-, 0.00 ± 0.00; MTB+/LBC-, 0.44 ± 0.51; MTB+/LBC+, 0.94 ± 0.24; p < 0.001). Moderate-to-severe IM was more common in MTB+/LBC+ areas than in MTB+/LBC- areas (p < 0.001). For the diagnosis of IM, MTB had a sensitivity, specificity, and accuracy of 100%, 66.0%, and 81.7%, respectively, and the corresponding values for LBC were 72.1%, 96.0%, and 84.9%.
MTB and LBC observed in the gastric mucosa with magnifying NBI endoscopy are highly accurate indicators of the presence of IM. MTB likely represents a sign of early gastric IM, while LBC appears with progression to severe IM.
PMCID: PMC3543218  PMID: 23185997
Stomach; Magnifying endoscopy; Intestinal metaplasia
16.  A prospective experimental study of liver fibrosis with ultrasound and its correlation with hepatic reserve function and hemodynamics 
BMC Gastroenterology  2012;12:168.
Progressive hepatic fibrosis is the eventual cause of liver cirrhosis. Doppler ultrasound has been used to detect hemodynamic changes that are known to be present during the pre-cirrhotic stages of hepatic fibrogenesis. However, the relationship between the Doppler ultrasound parameters and the impairment of the liver function has not been fully investigated. The purpose of this study was to explore the hepatic function reserve and its relationship with the hepatic hemodynamics in a rabbit model of liver fibrosis using Doppler ultrasound.
A prospective study was performed. Sixty healthy New Zealand rabbits were included in this study. Eleven of them served as controls and were normally fed and provided with water drink; the rest of 49 rabbits that served as fibrosis group were normally fed but provided with 1.2 g/L of thioacetamide to create liver fibrosis model. Doppler measurements were performed in the portal trunk, proper hepatic artery and proper splenic artery. The hepatic circulation index (HCI) was calculated. Hepatic function reverse was evaluated by measuring the indocyanine green clearance and retention rate at 15 min (ICG R15) test. Portal venous pressure (PVP) was measured using the portal vein punctuation equipment.
HCI was significantly decreased and PVP increased in the advanced fibrotic stage (F4) compared to mild and moderate fibrotic stage (F1-3), respectively (p<0.05). PVP and ICG R15 in the fibrotic group were significantly higher than that in the control group (ICG: 0.209±0.086 vs. 0.093±0.023, p<0.01). Within the fibrotic groups, PVP was higher in advanced fibrotic stage (F4) than those in mild (F1-2) or moderate (F3) fibrotic stages (p<0.05). Both HCI and PVP correlated well with ICG R15 (r = −0.890, and r = 0.780, p <0.01).
Hepatic function reserve closely relates to the hepatic hemodynamics in the rabbit model of liver fibrosis. Doppler Ultrasound could be reliably used to assess the hepatic function reserve and hemodynamic changes in different stages of liver fibrosis.
PMCID: PMC3526408  PMID: 23173929
Hepatic circulation index; Liver fibrosis; Hepatic function reserve; Doppler
17.  Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan 
BMC Gastroenterology  2012;12:167.
The aim of this study was to evaluate whether polymorphisms in the guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1) and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment (PEG-IFNα-RBV).
We analyzed the association between RVR to PEG-IFNα-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the GNB1 gene. This study included 265 HCV-1 and 195 HCV-2 infected patients in a Chinese population in Taiwan.
Among the GNB1 SNPs examined, the combination of genotypes G/G and G/T populations of rs12126768 was significant inversely correlated with RVR in HCV-1 infected patients (P = 0.0330), whereas HCV-2 infected patients, combination of A/A and A/C genotypes populations at rs4648727 responded better to the PEG-IFNα-RBV treatment (P = 0.0089). However, there were no significant differences in the allele frequencies of those SNPs between RVR responders and non-responders. Several RVR susceptibility GNB1 haplotypes were identified, and the ACAT haplotype of the 4 SNPs may increase the successful outcomes of HCV-1 and HCV-2 infected patients (P = 0.0261 and P = 0.0253, respectively).
The data for GNB1 SNPs and the association of RVR showed that GNB1 polymorphisms might be associated with the therapeutic outcomes of HCV-1 and HCV-2 infected patients under standard of care (SOC) treatment.
PMCID: PMC3536692  PMID: 23171003
Hepatitis C virus; Standard of care treatment; Rapid virological response; G protein
18.  IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population 
BMC Gastroenterology  2012;12:166.
Patients with Irritable Bowel Syndrome (IBS) often relate their symptoms to the intake of food and modify their diet. IgE-mediated food allergy is uncommon in IBS, but the role of IgG-mediated food hypersensitivity remains inconclusive. The primary aim of this study was to compare food- and yeast-specific IgG and IgG4 antibodies in subjects with and without IBS.
This was a case control study in the general population for which subjects completed questionnaires about abdominal complaints and their intake of common food items. Blood samples were collected, and food- and yeast-specific IgG and IgG4 antibodies were measured. Antibodies were measured in mg/L.
We included 269 subjects with IBS and 277 control subjects. After correction for subject characteristics and diet, there were no significant differences with regard to food- and yeast-specific IgG and IgG4 antibodies between subjects with IBS and controls. Lower values of IgG antibodies against egg (OR 0.99 (0.98 to 1.00), p = 0.002) and beef (OR 0.75 (0.60 to 0.94), p = 0.012) and higher values of IgG antibodies against chicken (OR 1.14 (1.03 to 1.27), p = 0.009) were associated with more severe symptoms.
Our findings suggest that IgG-and IgG4-mediated food and yeast hypersensitivity in IBS is unlikely. IgG antibodies against food and yeast may reflect the diet.
PMCID: PMC3526446  PMID: 23170971
Human; Adult; Irritable bowel syndrome; Cross-sectional studies; Diet; Gastrointestinal tract; Immunoglobulin G; Food Hypersensitivity
19.  Green tea consumption and risk of esophageal cancer: a meta-analysis of epidemiologic studies 
BMC Gastroenterology  2012;12:165.
Green tea has shown the role of chemoprevention for cancer. Recently, several studies suggested that green tea intake may have effect on esophageal cancer risk, whereas the results were inconsistent.
We performed a meta-analysis of all English and Chinese language studies of green tea consumption and esophageal cancer risk indexed in Medline, Embase, the Science Citation Index, the Chinese Biomedical Database and Wanfang Data from 1980 to June 2012. After reviewing each study, extracting data, and evaluating heterogeneity (Chi-square-based Q test and Ι2) and publication bias (Begg and Egger test), a meta-analysis was performed to evaluate the association between high/medium/low green tea consumption and non-drinking esophageal cancer risk. Pooled relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effect models.
Ten eligible epidemiologic studies including 33731 participants and 3557 cases for esophageal cancer were included. Eight of which were case–control studies, and two were cohort studies. Overall, there were no association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer (High: highest vs non-drinker: RR/OR = 0.76, 95% CI: 0.49 to 1.02. Medium: drinker vs non-drinker: RR/OR = 0.86, 95% CI: 0.70 to 1.03. Low: lowest vs non-drinker: RR/OR = 0.83, 95% CI: 0.58 to 1.08). When stratified analyses according to study design (case–control and cohort studies), country (China and Japan), participates source (population-based and hospital-based case–control), and gender (female and male), there were significant association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer among female (High: RR/OR = 0.32, 95% CI: 0.10 to 0.54. Medium: RR/OR = 0.43, 95% CI: 0.21 to 0.66. Low: RR/OR = 0.45, 95% CI: 0.10 to 0.79), but not the others.
We did not found significant association between green tea consumption and non-drinking esophageal cancer risk, but an evidence of protective effect was observed among female.
PMCID: PMC3573987  PMID: 23170950
20.  Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study 
BMC Gastroenterology  2012;12:164.
There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.
It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl.
A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared.
260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups.
This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case.
Trial registration
Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
PMCID: PMC3607964  PMID: 23170921
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
21.  HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b 
BMC Gastroenterology  2012;12:162.
The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.
For 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).
The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.
Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.
Trial registration Identifier: NCT01342003
PMCID: PMC3526494  PMID: 23157720
Genotype 1a; HCV genotype 1 subtypes; Sustained virological response; Antiviral therapy; Pegylated interferon
22.  Rumination syndrome in children and adolescents: a school survey assessing prevalence and symptomatology 
BMC Gastroenterology  2012;12:163.
Rumination syndrome (RS) is a functional gastrointestinal disorder (FGD) increasingly recognized in children and adolescents. The epidemiology of this condition in school aged children is poorly understood. The main objective of this study was to assess the prevalence of rumination and other related associations in a cohort of Sri Lankan children.
Children aged 10-16 years were randomly selected from 8 schools in 4 provinces in Sri Lanka. RS was diagnosed using Rome III criteria. Data was collected using a self administered questionnaire distributed in an examination setting. It was translated into Sinhala, the native language and pretested before distribution.
A total of 2163 children were included in the study (55% boys, mean age 13.4 years, SD 1.8 years). Prevalence of RS was 5.1% (n = 110); boys 5.1% and girls 5.0%. When symptoms were analyzed, 73.6% reported re-swallowing of regurgitated food, while the rest spat it out. In 94.5% regurgitation occurred during the first hour after the meal. Only 8.2% had daily symptoms while 62.7% had symptoms weekly. Abdominal pain, bloating and weight loss were the commonest symptoms associated with RS (19.1%, 17.3% and 11.8% respectively). No significant association was observed between exposure to stressful events and rumination (p > 0.05). Twenty (18.2%) with RS fulfilled Rome III criteria for at least one other FGD. School absenteeism was seen in 11.8% of affected children.
RS was reasonably common in this cohort of school-aged children and adolescents in Sri Lanka. However, symptoms were severe enough to affect schooling only in 12% of affected children. Around one fifth with RS had at least one other overlapping FGD.
PMCID: PMC3538663  PMID: 23157670
Adolescent; Child; Epidemiology; Functional gastrointestinal disorder; Rumination syndrome
23.  Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma 
BMC Gastroenterology  2012;12:160.
The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy.
In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot.
ABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (p<0.01). The gene expression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4 than in well-differentiated G1/G2 HCC.
Our results suggest a correlation of ABCG2 gene expression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors.
PMCID: PMC3538657  PMID: 23153066
Liver cancer; Drug resistance; Gene expression; Doxorubicin
24.  Prevalence and risk factors of gastroesophageal reflux symptoms in a Chinese retiree cohort 
BMC Gastroenterology  2012;12:161.
Data about prevalence of gastroesophageal reflux diseases (GERD) from Asian populations are still scarce. To provide additional data on prevalence of GERD and investigate its potential risk factors, we performed this cross-sectional study in the Taizhou Retiree Cohort.
After physical examination, the participants were asked whether they suffered with heartburn or acid regurgitation in the last 12 months by trained interviewers, and if yes, the severity and frequency of the symptoms were recorded. Odds ratios (ORs) with 95% confidence intervals (CIs) for the associations of obesity and other risk factors with GERD were derived from logistic regression models.
8831 retirees completed the questionnaire and physical examination. In total 150 (1.7%) reported the symptoms occurring at least once per week within the last 12 months before the interview. Compared with subjects without GERD, having a history of diabetes mellitus (OR 2.2, 95% CI 1.4-3.5), hypertension (OR 1.4, 95% CI 1.0-2.1), gastritis (OR 8.2, 95% CI 5.8-11.5), peptic ulcer (OR 3.3, 95% CI 1.8-6.1) and high triglyceride level (≥1.81mmol/L) (OR 2.0, 95% CI 1.2-3.4) were associated with a significantly increased risk of GERD. However, there was no significant association between body mass index, waist-to-hip ratio or waist alone, smoking, consumption of alcohol & tea, and the occurrence of reflux symptoms.
Compared with Western populations, the prevalence of GERD in this Chinese retiree cohort is low. A history of diabetes mellitus, hypertension, gastritis, peptic ulcer or hypertriglyceridaemia increases GERD risk in this population.
PMCID: PMC3573958  PMID: 23153099
Gastroesophageal reflux symptoms; Body mass index; Obesity; Abdominal obesity; Retired population
25.  Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype 
BMC Gastroenterology  2012;12:158.
IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.
Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.
Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.
IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.
PMCID: PMC3503804  PMID: 23145809
IL28B; ITPA; Splenectomy; Liver cirrhosis

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