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1.  Effect of statin use on outcome of symptomatic cholelithiasis: a case-control study 
BMC Gastroenterology  2014;14:119.
Statins can modify bile cholesterol and, thus, the formation of gallstones. We examined whether statin use also modifies the severity of symptomatic gallstone disease and its treatment.
A total of 1,140 consecutive patients with symptomatic gallstone disease were recruited during 2008-2010 at Kuopio university hospital, Finland. Case-control analysis matched the patients using (n = 272) or not using (n = 272) statins by age and sex. The baseline characteristics of the patients, need and type of surgical treatment, duration of operation, perioperative bleeding, postoperative complications and overall mortality rate were compared statistically between the study groups.
Morbidity and subsequent polypharmacy occurred more frequently among the patients with statins compared to the patients without statins. There were no significant differences between the statin users and non-users regarding surgical treatment (open vs. laparoscopic cholecystectomy). The mean operation time for laparoscopic cholecystectomy was 10% shorter for the patients with statin use than for the patients without. In addition, there was a non-significant tendency for statin users to bleed less during laparoscopic operations than the non-users. There were no differences in other procedure-related parameters (e.g., operation urgency, conversions, choledochotomies, complications and mortality) in patients with or without statins.
Compared to no treatment, statin treatment was associated with a shorter operation time for laparoscopy cholecystectomy. Other surgical outcome parameters were similar in patients with or without statins, although statin users had more polypharmacy and circulatory illnesses than non-users.
PMCID: PMC4086267  PMID: 24993977
Cholelithiasis; Statins; Cholecystectomy
2.  Gastrinoma and neurofibromatosis type 2: the first case report and review of the literature 
BMC Gastroenterology  2014;14:110.
Gastroenteropancreatic neuroendocrine tumors have occasionally been described in association with neurofibromatosis type 1, whereas an association with neurofibromatosis type 2 has never been reported.
Case presentation
This report refers to an Italian 69 year old woman with neurofibromatosis type 2 and a pancreatic gastrinoma. In the past she had encephalic meningiomas, a tongue schwannoma and bilateral acoustic neurinomas. She presented with weight loss and a long-term history of diarrhea, responsive to proton pump inhibitors. Upper gastrointestinal endoscopy revealed peptic ulcer of the duodenal bulb. Blood tests were normal, except for the elevation of plasma gastrin (1031 pg/ml; reference value <108) and chromogranin A (337 U/L; reference value <36). After secretin stimulation testing, the plasma gastrin level rose to 3789 pg/ml. The abdomen magnetic resonance imaging and gallium68-DOTATOC positron emission tomography scan demonstrated the presence of a 1.2 x 2 cm lesion in the pancreatic head and a liver metastatis. Pancreatic endoscopic ultrasound with fine needle aspiration revealed cytomorphologic features suggestive of pancreatic gastrinoma. Brain magnetic resonance showed a pituitary microadenoma. There was no evidence of hyperparathyroidism. The genetic test for multiple endocrine neoplasia type 1 syndrome mutation was negative.
This report focuses on the first case of coexistence of gastrinoma with neurofibromatosis type 2. Although the clinical relevance of this association remains to be determined, our case report will surely give cause for due consideration.
PMCID: PMC4082280  PMID: 24961548
Gastrinoma; Neurofibromatosis type 2; Multiple endocrine neoplasia syndrome type 1; Neuroendocrine tumors; Zollinger Ellison syndrome
3.  Hepatobiliary cystadenocarcinoma without mesenchymal stroma in a female patient: a case report 
BMC Gastroenterology  2014;14:109.
Hepatobiliary cystadenocarcinoma is a rare epithelial malignant neoplasm of the liver or extrahepatic bile ducts. Early diagnosis of hepatobiliary cystadenocarcinoma is difficult because of its asymptomatic features and rarity. Moreover, the molecular pathogenesis of hepatobiliary cystadenocarcinoma remains unclear. Herein, we described a case of hepatobiliary cystadenocarcinoma in female with chronic hepatitis B and repeated hepatolithiasis.
Case presentation
A 65-year-old woman with medical history of latent hepatitis B virus infection, repeated choledocholisthiasis, and cholecystitis was admitted due to a heterogeneous cystic mass (5.6 cm × 4 cm) shown on abdominal ultrasonography during regular physical checkup. The patient complained about irregular bowel movements with intermittent diarrhea for two months before presentation. Computed tomography (CT) disclosed a multiloculated cystic lesion in the left hepatic lobe with the presence of intraductal stones and dilatation of intrahepatic ducts. Histological results obtained from left lobectomy specimens showed hepatobiliary cystadenocarcinoma without accompanied mesenchymal stroma.
Notably, hepatobiliary cystadenocarcinoma without mesenchymal stroma seldom occurs in women and is usually associated with poor prognosis. We present the rare findings in this patient and suggest that chronic inflammatory insults in the intrahepatic bile ducts might shed light on the cystadenocarcinogenesis.
PMCID: PMC4065581  PMID: 24934314
Hepatobiliary cystadenocarcinoma; Biliary tumors; Hepatolithiasis; Cholestasis
4.  Intestinal obstruction due to dual gastrointestinal atresia in infants: diagnosis and management of 3 cases 
BMC Gastroenterology  2014;14:108.
Several types of congenital lesions can cause complete or incomplete obstruction of the intestine. Our purpose is to present 3 neonates with dual intestinal type I atresia, i.e., simultaneous obstructive lesions at 2 locations in which the atresia manifested as diaphragm-like tissue.
Case presentation
All 3 cases were female infants ranging in age from 2 to 14 months. The common symptom in all cases was intermittent persistent vomiting. In some cases the vomitus was bilious, and other symptoms included abdominal distention and delayed meconium passage. Prior surgeries at another hospital were unsuccessful at relieving the symptoms in one case. One case had dual lesions in the colon, one dual lesions in the duodenum, and one atresia at both the distal portion of the ileum and the descending colon. Surgical exploration and removal of the lesions at our hospital was successful in all cases, and the infants were discharged in good condition.
Type I atresia can manifest as a diaphragm-like tissue obstructing the continuity of gastrointestinal tract, and in rare cases multiple areas may be present. Base on the intermittent nature of the associated symptoms, diagnosis can be difficult and is often delayed. Physicians should be aware of this condition during the work-up of an infant with persistent intermittent vomiting.
PMCID: PMC4064280  PMID: 24928109
Type I Atresia; Gastrointestinal diaphragm; Congenital; Intestinal obstruction; Infant
5.  Chronic stress induces steatohepatitis while decreases visceral fat mass in mice 
BMC Gastroenterology  2014;14:106.
Prolonged stress leads over time to allostatic load on the body and is likely to exacerbate a disease process. Long-term of stress exposure is one of a risk factor for metabolism-related diseases such as obesity and type 2 diabetes. However, the relationship between chronic stress and non-alcoholic fatty liver disease (NAFLD) remain unknown.
To address the hypothesis that chronic stress associate to NAFLD development, we subjected C57bl/6 mice to electric foot shock and restraint stress for 12 weeks to set up chronic stress model. Then the serum and hepatic triglyceride (TG), total cholesterol (TC) were measured. Hepatic HE and Oil red O staining were used to specify the state of the NAFLD. To investigate whether inflammation takes part in the stress-induced NAFLD process, related visceral fat, serum and hepatic inflammatory factors were measured.
We observed that chronic stress led to an overall increase of hepatic triglyceride and cholesterol while decreasing body weight and visceral fat mass. Microvesicular steatosis, lobular inflammation and ballooning degeneration were seen in stress liver section. This effect was correlated with elevated hepatic and serum inflammatory factors. Although the amount of visceral fat was decreased in stress group, various adipocytokines were elevated.
We showed that chronic stress is associated to NAFLD and chronic inflammation in visceral fat, though food intake and visceral fat mass were decreased. These results may contribute to better understanding of the mechanism from steatosis to steatohepatitis, and propose a novel insight into the prevention and treatment of NAFLD.
PMCID: PMC4070165  PMID: 24916323
Chronic stress; Homeostasis; Steatosis; Inflammation; Visceral fat
6.  Clinical and psychosocial variables associated with behavioral intentions to undergo surveillance endoscopy 
BMC Gastroenterology  2014;14:107.
Many patients with Barrett’s esophagus do not adhere to guideline-recommended endoscopic surveillance. Among patient factors related to cancer prevention behaviors, patients’ stated behavioral intention is a strong predictor of behavior performance. Little is known about the patient factors associated with having a strong behavioral intention to pursue surveillance endoscopy. This study explores the association of clinical and psychosocial variables and behavioral intention to pursue surveillance endoscopy among patients with Barrett’s Esophagus and no or low-grade dysplasia.
Potential subjects were screened using electronic medical records of a regional Veterans Affairs Medical Center and a pathologically confirmed Barrett’s esophagus registry. Eligible participants were recruited by a mailer or phone call and completed a questionnaire to measure six distinct psychosocial factors, their behavioral intention to undergo surveillance endoscopy, and various demographic and clinical variables. Univariate and multivariate linear regression identified the relation of behavioral intention with each of six psychosocial variables.
One-hundred and one subjects consented and returned surveys. The analytical sample for this study consists of the 94% of surveys with complete responses to the behavior intention items. Three of the six psychosocial domains were statistically significant predictors of intention in both univariate and adjusted univariate analysis (salience/coherence β = 0.59, 95% CI = 0.45-0.76, P <0.01; self-efficacy β = 0.30, 95% CI = 0.10-0.51, P <0.01; and social influence β = 0.20, 95% CI = 0.08-0.33, P <0.01). In a multivariate analysis only salience/coherence (β = 0.65, 95% CI = 0.42-0.88, P <0.01) remained statistically significant predictor of intention.
This study established the validity of a scale to measure psychosocial variables associated with behavioral intentions to undergo surveillance endoscopy. Results demonstrate the importance of assessing self-efficacy, social influences, and bottom-line belief in the value of surveillance endoscopy when evaluating a patient’s likelihood of completing surveillance endoscopy.
PMCID: PMC4079921  PMID: 24916457
Barrett’s esophagus; Surveillance; Intention; Endoscopy
7.  Evaluation of high-risk clinicopathological indicators in gastrointestinal stromal tumors for prognosis and imatinib treatment outcome 
BMC Gastroenterology  2014;14:105.
Although the clinical benefit of imatinib adjuvant therapy for high-risk patients with gastrointestinal stromal tumor (GIST) has been proven, the recurrence rate still remains high. This study aimed to sub-divide high-risk GIST patients with some “very high-risk” factors for more precise prognostic indicator, and possible association with efficiency of imatinib adjuvant therapy.
Clinicopathological data were confirmed by pathological diagnosis and clinical records. Recurrence-free survivals (RFS) were evaluated in 370 GIST patients (212 cases as test cohort and 158 cases as validation cohort) and 48 high-risk GISTs with imatinib adjuvant therapy after R0 resection.
Mitosis count > 10/50 high-power fields (HPF) and serosal invasion are independent prognostic factors for RFS of GIST patients. Mitosis count > 10/50HPF and serosal invasion can sub-divide high-risk GIST patients effectively and significantly improve the area under the curve (AUC) of receiver operating characteristics (ROC) curve for prognostic indicator both in test and validation cohort. Patients with serosal invasion after R0 resection showed a poorer prognosis with imatinib adjuvant therapy.
Sub-division of high-risk GIST patients helps to more precisely predicting the prognosis. Serosal invasion may be an adverse predictive factor in high-risk patients and imatinib treatment outcome.
PMCID: PMC4057930  PMID: 24906683
Gastrointestinal stromal tumor; Mitosis; Serosal invasion; Prognosis
8.  Clinical impact of body mass index on bactibilia and bacteremia 
BMC Gastroenterology  2014;14:104.
The aim of this study was to evaluate the association between obesity and infected bile or bacteremia in patients with acute calculous cholecystitis.
Authors analyzed the medical records of 139 patients who had undergone cholecystectomy for the treatment of acute calculous cholecystitis from January 2007 to June 2013 in a single teaching hospital. Association of body mass index (BMI) with bactibilia and bacteremia was assessed using univariate and multivariate analysis. Clinical findings and biliary infection related data were recorded for the following variables: gender, age, alcohol and smoking history, the results of blood and bile cultures, cholesterolosis, diabetes, hypertension, and duration of the hospital stay.
The microbial culture rate of bactibilia and bacteremia were 50.4% and 21.6%, respectively. In the univariate analysis, bacteremia was associated with bactibilia (OR: 4.33, p = 0.002). In the multivariate analysis for the risk factors of bactibilia, BMI and bacteremia were related with bactibilia (OR: 0.59, 95% CI: 0.42-0.84, p = 0.003) (OR: 3.32, 95% CI: 1.22-9, p = 0.02). In the multivariate analysis for the risk factors of bacteremia, BMI, bactibilia and age were related with bacteremia (OR: 0.76, 95% CI: 0.59-0.99, p = 0.04) (OR: 3.46, 95% CI: 1.27-9.45, p = 0.02) (OR: 1.05, 95% CI: 1.01-1.09, p = 0.02).
In this retrospective study, BMI was inversely correlated with bacteremia or bactibilia, which means obese or overweight patients are less likely to be associated with bacteremia or bactibilia in patients with acute calculous cholecystitis.
PMCID: PMC4073193  PMID: 24902609
Bacteremia; Cholecystitis; Obesity
9.  A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation 
BMC Gastroenterology  2014;14:103.
Oral iron supplementation is often associated with rapid onset of gastrointestinal side-effects. The aim of this study was to develop and trial a short, simple questionnaire to capture these early side-effects and to determine which symptoms are more discriminating.
The study was a double-blind placebo-controlled randomized parallel trial with one week treatment followed by one week wash-out. Subjects were randomized into two treatment groups (n = 10/group) to receive either ferrous sulphate (200 mg capsules containing 65 mg of iron) or placebo, both to be taken at mealtimes twice daily during the treatment period. Subjects completed the questionnaires daily for 14 days. The questionnaire included gastrointestinal symptoms commonly reported to be associated with the oral intake of ferrous iron salts (i.e. nausea, vomiting, heartburn, abdominal pain, diarrhoea, and constipation).
Seventy five per cent of participants reporting the presence of one or more symptoms in the first week of the study were in the ferrous sulphate group. In the second week of the study (i.e. wash-out), 67% of the participants reporting one or more symptom(s) were in the ferrous sulphate group. In the first week of the study (treatment) the number of symptoms reported by participants in the ferrous sulphate group (mean ± SEM = 6.7 ± 1.7) was significantly higher than that for participants in the placebo group (1.2 ± 0.5) (p = 0.01). In the second week of the study (wash-out) the number of symptoms reported by participants in the ferrous sulphate group (4.6 ± 2.0) appeared higher than for participants in the placebo group (1.0 ± 0.7) although this did not reach significance (p = 0.12). Events for which the gastrointestinal symptom questionnaire was most discriminatory between ferrous sulphate and placebo groups were: heartburn, abdominal pain and the presence of black stools (all p ≤ 0.03).
A tool for the detection of commonly-occurring side effects should not require large study numbers to be effective. With just 10 subjects per group (iron or placebo), this simple questionnaire measures gastrointestinal side-effects associated with oral iron (ferrous sulphate) supplementation, and would be appropriate for use in intervention studies or clinical trials.
Trial registration Identifier: NCT02146053 (21/05/2014).
PMCID: PMC4082414  PMID: 24899360
Gastrointestinal symptoms; Ferrous sulphate; Iron supplementation; Side-effects; Adverse events; Oral iron
10.  Impact of clinical experience on type V pit pattern analysis using magnifying chromoendoscopy in early colorectal cancer: a cross-sectional interpretation test 
BMC Gastroenterology  2014;14:100.
Although type V pit pattern analysis is effective in determining the invasion depth of early colorectal cancers, the clinical results may vary because findings are operator-dependent. This study aimed to assess the benefits of type V pit pattern analysis in estimating the invasion depth using magnifying chromoendoscopy compared to that with conventional colonoscopy.
A cross-sectional interpretation test involving 32 endoscopists with varying levels of experience performing colonoscopies was conducted. Fifty histopathologically diagnosed cases of intramucosal or submucosal cancer were selected retrospectively. The lesions were classified as superficial or deep by the endoscopists, based on magnifying chromoendoscopic and non-magnifying endoscopic images. The endoscopists were classified into 3 groups based on the number of colonoscopies performed: I (<500), II (501–5000), and III (>5000). Differences in the interpretation of invasion depth between group III and groups I and II were assessed using the Mann–Whitney U test.
There was no significant difference in the median number of correct interpretations using non-magnifying endoscopic images among the groups. However, a significant difference (P = 0.007) was observed between the results of groups III and I when the analysis was performed using magnifying chromoendoscopic images.
When performed by less experienced endoscopists, pit pattern analysis of colonic lesions using magnifying chromoendoscopy is not a reliable modality for estimating invasion depth in early colorectal cancer.
PMCID: PMC4046150  PMID: 24885943
Magnifying chromoendoscopy; Early colorectal cancer; Pit pattern; Type V pit
11.  Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis 
BMC Gastroenterology  2014;14:101.
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.
PMCID: PMC4057999  PMID: 24886123
Esophageal cancer; Physical activity; Exercise; Prevention; Barrett’s esophagus
12.  Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis 
BMC Gastroenterology  2014;14:102.
The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications.
We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (,, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis.
Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction.
The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.
PMCID: PMC4061927  PMID: 24886242
Acute pancreatitis; Protease inhibitors; Mortality; Control mortality rate; Complication
13.  Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease 
BMC Gastroenterology  2014;14:99.
The consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis.
Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls.
No differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p < 0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there was no difference.
No major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet.
PMCID: PMC4046848  PMID: 24885742
Coeliac; Diabetes; Glycaemic control; Growth; Nutrition
14.  High glucose increases LPS-induced DC apoptosis through modulation of ERK1/2, AKT and Bax/Bcl-2 
BMC Gastroenterology  2014;14:98.
This study investigates the effect of glucose on the LPS-induced apoptosis of dendritic cells in the intestinal tract of mice and the dendritic cell line DC2.4.
Flow cytometry was used to detect dendritic cell apoptosis both in vivo and in vitro. Hoechst 33258 staining was used to detect the morphological changes characteristic of apoptotic nuclei. Expression of apoptosis related proteins was investigated by western blot analysis and immunohistochemistry.
Pretreatment with a high concentration of glucose increased apoptosis of LPS-treated dendritic cells both in vivo and in vitro at 24 h. No effect was evident at the earlier time points of 15 min and 6 h in vitro. Furthermore, at 24 hours the expression of the survival proteins AKT, ERK and Bcl-2 was decreased, while the expression of the proapoptotic protein Bax was increased. AKT, ERK, Bcl-2 and Bax were mainly located in the cytoplasm by immunohistochemistry.
These results suggest that high glucose concentrations might prime dendritic cells for apoptosis induced by LPS in the intestinal tract through upregulating the expression of Bax and downregulating the expression of AKT, ERK and Bcl-2. Therefore, this study may give clues to understanding the immunological mechanism behind gastrointestinal complications in diabetes mellitus.
PMCID: PMC4081508  PMID: 24885625
Dendritic cell; Apoptosis; Diabetes mellitus; Glucose; Gastrointestinal complications diabetes
15.  Diagnostic sensitivity of carbohydrate deficient transferrin in heavy drinkers 
BMC Gastroenterology  2014;14:97.
Background and Aim
Carbohydrate deficient transferrin (CDT) is the most specific serum biomarker of heavy alcohol consumption, defined as ≥ 350–420 g alcohol/week. Despite introduction of a standardized reference measurement technique, widespread use of CDT remains limited due to low sensitivity. The aim of this study was to determine the factors that affect diagnostic sensitivity in patients with sustained heavy alcohol intake.
Patients with a self-reported history of sustained heavy alcohol consumption were recruited from the hepatology outpatient department or medical wards. Each patient was interviewed with a validated structured questionnaire of alcohol consumption and CDT analysis using the standardized reference measurement technique with high performance liquid chromatography was performed on serum collected at time of interview.
52 patients were recruited: 19 from the hepatology outpatient department and 33 from general medical wards. Median alcohol intake was 1013 (range 366–5880) g/week over the preceding two week period. 26 patients had a diagnostic CDT based on a threshold value of %CDT > 1.7 indicating heavy alcohol consumption, yielding a sensitivity of 50%. Overweight/obesity (defined as body mass index (BMI) ≥ 25 kg/m2 in Caucasians and ≥ 23.0 kg/m2 in Asians), female gender and presence of cirrhosis were independently associated with non-diagnostic %CDT (≤ 1.7).
CDT has limited sensitivity as a biomarker of heavy alcohol consumption. Caution should be applied when ordering and interpreting %CDT results, particularly in women, patients with cirrhosis and those with an elevated BMI.
PMCID: PMC4042141  PMID: 24885510
Alcohol; High performance liquid chromatography; Cirrhosis; Biomarker; Obesity
16.  Up-regulation of CNDP2 facilitates the proliferation of colon cancer 
BMC Gastroenterology  2014;14:96.
Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis.
We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena.
The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E.
Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.
PMCID: PMC4035726  PMID: 24885395
CNDP2; Colon cancer; Poliferation; Clinicopathological Characteristics; RNA interference
17.  Prevalence of faecal incontinence and its related factors among patients in a Malaysian academic setting 
BMC Gastroenterology  2014;14:95.
Prevalence data is essential for planning of healthcare services. The prevalence of faecal incontinence (FI) varies worldwide, and in Malaysia is not known. We sought to estimate its prevalence among patients with various conditions in a Malaysian academic setting.
A questionnaire-based survey was conducted among a convenience sample of adult patients and relatives who visited the Obstetrics and Gynaecology and General Surgery Clinics of University of Malaya Medical Centre (UMMC) from June 2009 to February 2010. Data collected included patient demographics and pre-existing medical conditions known to be FI risk factors. Severity of FI was assessed using the Wexner Continence Scale (WCS).
Among the 1000 subjects recruited into the study, 760 (76%) were female and the median age was 38 years with an inter-quartile range of 24 years. The prevalence of FI among the study subjects was found to be 8.3%. Among them, 63 subjects (75.9%) were determined to have mild FI as measured by the WCS. The proportions of patients with moderate and severe FI were 18.3% and 6.0%, respectively. FI was found to be significantly associated with older age, presence of diabetes mellitus and increased duration of defaecation. There was no statistically significant association between FI and sex, defaecation frequency, or history of surgery.
FI in our setting is prevalent enough to warrant targeted healthcare interventions, including the need to improve general public awareness of the condition in order to counter social stigma and embarrassment that may be faced by patients.
PMCID: PMC4029879  PMID: 24885285
Faecal incontinence; Prevalence; Sphincter defects; Soiling; Constipation
18.  Coexistence of HBsAg and HBsAb in a difficult-to-treat chronic hepatitis B: loss of HBsAg with entecavir plus tenofovir combination 
BMC Gastroenterology  2014;14:94.
Some reports have documented the coexistence of Hepatitis B surfage Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological escape variant.
HBV genome has a very compact coding organization, with four partially overlapping open reading frames (ORFs). Because the reverse transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is possible that some mutations in the HBsAg region correspond to mutations in the rt ORF, conferring resistance to current antiviral therapies.
This unique case explores the response to antiviral therapies of a CHB with concurrent HBsAg and HBsAb positivity, and analyse the clinical implications of possible mutations in rt and HBsAg ORFs.
Case presentation
Here we describe the case of a 59 year-old Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with concurrent HBsAb positivity. By ultra-deep pyro-sequencing (UDPS) technique, mutations conferring immunological escape or resistance to antiviral therapies were found neither in HBsAg nor in HBV rt ORFs, respectively.
The patient was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combination. Surprisingly, during entecavir plus tenofovir combination, anti-HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb persisted.
Concurrent HBsAg/HBsAb positivity in active CHB is a clinical and virological dilemma. In this setting, there are not consistent data about the response to conventional therapies and the immunological balance between host and virus remains so far unexplained. This is, to our knowledge, the first case described of a CHB with HBsAg/HBsAb positivity, wild type for clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a combination of nucleot(s)ide analogues (NAs).
PMCID: PMC4031327  PMID: 24885182
HBeAg positive chronic hepatitis B; HBsAg; Anti-HBs; Coexistence; Ultra-deep pyro-sequencing; Immunological escape; Nucleos(t)ide analogues; Combination; Entecavir; Tenofovir
19.  Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children 
BMC Gastroenterology  2014;14:93.
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.
PMCID: PMC4037749  PMID: 24885054
Paneth cell; Metaplasia; Paediatric; Ulcerative colitis; Crohn’s disease
20.  Sigmoid colon cancer arising in a diverticulum of the colon with involvement of the urinary bladder: a case report and review of the literature 
BMC Gastroenterology  2014;14:90.
Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images.
Case presentation
A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum.
The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.
PMCID: PMC4030041  PMID: 24884743
Colon cancer; Diverticulum; Urinary bladder invasion
21.  Acid suppressive agents and risk of Mycobacterium Tuberculosis: case–control study 
BMC Gastroenterology  2014;14:91.
The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported.
We conducted a case–control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed.
TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended.
Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.
PMCID: PMC4030068  PMID: 24884853
Proton pump inhibitor; Histamine2-receptor antagonist; Mycobacterium Tuberculosis; National health insurance database; Taiwan
22.  Increasing late stage colorectal cancer and rectal cancer mortality demonstrates the need for screening: a population based study in Ireland, 1994-2010 
BMC Gastroenterology  2014;14:92.
This paper describes trends in colorectal cancer incidence, survival and mortality from 1994 to 2010 in Ireland prior to the introduction of population-based screening.
We examined incidence (National Cancer Registry Ireland (NCRI) and mortality (Central Statistics Office) from 1994 to 2010. Age standardised rates (ASR) for incidence and mortality have been calculated, weighted by the European standard population. Annual percentage change was calculated in addition to testing for linear trends in treatment and case fraction of early and late stage disease. Relative survival was calculated considering deaths from all causes.
The colorectal cancer ASR was 63.7 per 100,000 in males and 38.7 per 100,000 in females in 2010. There was little change in the ASR over time in either sex, or when colon and rectal cancers were considered separately; however the number of incident cancers increased significantly during 1994-2010 (1752 to 2298). The case fractions of late stage (III/IV) colon and rectal cancers rose significantly over time. One and 5 year relative survival improved for both sexes between the periods 1994-2008. Colorectal cancer mortality ASRs decreased annually from 1994-2009 by 1.8% (95% CI -2.2, -1.4). Rectal cancer mortality ASRs rose annually by 2.4% (95% CI 1.1, 3.6) and 2.8% (95% CI 1.2, 4.4) in males and females respectively.
Increases in late-stage disease and rectal cancer mortality demonstrate an urgent need for colorectal cancer screening. However, the narrow age range at which screening is initially being rolled-out in Ireland means that the full potential for reductions in late-stage cancers and incidence and mortality are unlikely to be achieved. While it is possible that the observed increase in rectal cancer mortality may be partly an artefact of cause of death misclassification, it could also be explained by variations in treatment and adherence to best practice guidelines; further investigation is warranted.
PMCID: PMC4041914  PMID: 24884929
Colorectal; Cancer; Ireland; Incidence; Survival; Mortality; Mass screening; Colon; Rectal
23.  Fast food diet with CCl4 micro-dose induced hepatic-fibrosis –a novel animal model 
BMC Gastroenterology  2014;14:89.
Non-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of conditions ranging from hepatocellular steatosis to steatohepatitis and fibrosis, progressing to cirrhosis, which occur in the absence of excessive alcohol use. Several animal models capture aspects of NAFLD but are limited either in their representation of the disease stages or use for development of therapeutics due to the extended periods of time required to develop full histological features.
Here, we report the development of a novel rat model for NAFLD that addresses some of these limitations. We used a fast food diet (FFD) and a CCl4 micro dose (0.5 ml/kg B.wt) for 8 weeks in Wistar rats. Serological analyses, gene expression profiling and liver histology studies were conducted to investigate the development of steatosis, steatohepatitis and fibrosis in the FFD-CCl4 model when compared to the individual effects of a FFD or a micro dose of CCl4 in rats.
The serum biochemical profile of the FFD-CCl4 model showed an increase in liver injury and fibrosis. This was also accompanied by a significant increase in liver triglycerides (TG), inflammation and oxidative stress. Importantly, we observed extensive fibrosis confirmed by: i) increased gene expression of fibrosis markers and, ii) moderate to severe collagen deposition seen as perisinusoidal and bridging fibrosis using H&E, Trichome and Sirius Red staining.
In summary, we find that the FFD-CCl4 rat model developed NAFLD histological features including, steatosis, inflammation and fibrosis in 8 weeks showing promise as a model that can be used to develop NAFLD therapeutics and liver anti-fibrotics.
PMCID: PMC4036109  PMID: 24884574
24.  Can the type of gallstones be predicted with known possible risk factors?: a comparison between mixed cholesterol and black pigment stones 
BMC Gastroenterology  2014;14:88.
Pathogenesis of gallstones (GS) is multifactorial and multiple genetic and environmental factors have been identified in different populations for different types of GS with varying prevalence. However the role of the each aetiological factor on the formation of mixed cholesterol and black pigment GS has not being addressed adequately. Hence in this study we attempted to compare known possible risk factors for mixed cholesterol and black pigment GS among two groups of patients with two types of GS.
The study was done on a cohort of patients with symptomatic GS admitted to the Teaching Hospital Peradeniya, Sri Lanka over a period of 18 months. Clinical and epidemiological data and physical parameters of the patients were recorded and surgically removed GS were analyzed chemically and physically to identify the type of GS. In addition lipid profile was done in all the patients with normal serum bilirubin levels.
A total of 86 patients were included in the study. Mixed cholesterol GS was significantly common among females than males (χ2 test, p = 0.029). Mixed cholesterol GS was commonly seen among patients belonging to Moor ethnicity (χ2 test, p = 0.009). Majority of patients with mixed cholesterol GS had body mass index above 25 kg/m2 (χ2 test, p = 0.018). Black pigment GS were significantly common among patients with type II diabetes mellitus (Fisher’s exact test, p = 0.035). Further all the patients with chronic haemolytic anaemia and alcoholic cirrhosis had black pigment GS. Age, family history, Fasting Blood Glucose, dyslipidaemia, lipid profile, parity and use of oral contraceptive pills in females, smoking and alcohol intake in males did not differ significantly among patients in the two groups.
Gender, ethnicity and body mass index can be used to predict the formation of mixed cholesterol GS and black pigment GS.
PMCID: PMC4017087  PMID: 24884475
Gallstones; Risk factors; Mixed cholesterol; Black pigment
25.  Presentation, aetiology and treatment of adult intussusception in a tertiary Sub-Saharan Hospital: a 10-year retrospective study 
BMC Gastroenterology  2014;14:86.
Adult intussusception is a rare clinical condition worldwide. It contributes to less than 5% of all cases of intussusception. Few studies have been conducted in low-income countries compared to high-income countries; particularly Sub-Saharan Africa. Based on anecdotal evidence, the authors hypothesized that the condition is not as rare in a Sub-Saharan setting in comparison with western countries. We set out to conduct the first review study of adult intussusception in Uganda.
The medical records of 37 (out of a total of 62 cases) adolescent and adult patients with a postoperative diagnosis of intussusception at Mulago National Referral and Teaching Hospital, from January 2003 to December 2012, were analyzed. The clinical features, diagnosis, treatment and pathologic features of lesions for these patients were reviewed. Intraoperative findings were described with reference to: the site of the intussusception, and the triggering lesion (either idiopathic or with a lead point).
The mean age was 33.6 years, with a range of 13 – 72 years. The male to female ratio was 1.85:1. The mean number of days for which symptoms had been present prior to presentation was 6.3 days, while the median was 4 days. All 37 patients presented with abdominal pain. Only 13 (35.1%) had the classical paediatric triad of abdominal pain, a palpable abdominal mass and bloody stool. Most of the remaining patients presented sub-acutely with non-specific symptoms. A lead point was present in 28 patients (75.7%). Of these, 24 (64.9%) cases involved tumours. Among the tumours, 54.2% were malignant. Treatment did not involve intussusception reduction in 14 patients (37.8%). Some form of operative surgery was conducted in 31 (83.8%) patients; mainly segmental bowel resections and hemi-colectomies.
Adult intussusception is uncommon in the Uganda, though probably less so than in western countries. It presents sub-acutely or chronically and is often diagnosed at laparotomy. Lead points are the triggering lesion most times and are due mainly to tumours. The bulk of tumours are malignant. Most patients require surgical resection, with prior reduction done in selected cases.
PMCID: PMC4016697  PMID: 24886558
Adult intussusception; Sub-acute and chronic symptoms; Tumour; Malignancies; Lead point; Idiopathic; Reduction; Resection

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