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1.  Faecal short-chain fatty acids - a diagnostic biomarker for irritable bowel syndrome? 
BMC Gastroenterology  2016;16:51.
Background
The diagnosis of irritable bowel syndrome (IBS) relies on symptom-based criteria. A valid and reliable biomarker that could confirm the diagnosis is desirable. This study evaluated the properties of faecal short-chain fatty acids (SCFA) as diagnostic biomarkers for IBS.
Methods
Twenty-five subjects with IBS and 25 controls were included in this explanatory case–control study. Stool samples were analysed for SCFA (acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid) with gas chromatography and reported as mmol/l and molar%. In the search for the best way to distinguish between subjects with and without IBS, the total amount and the amount of each of the SCFA were measured, and the proportions and differences between the SCFA were calculated.
Results
In the IBS and control group, the mean age was 46.2 (SD 12.9) and 49.2 (SD 14.6), and the number of females was 13/25 (52 %) and 15/25 (60 %) respectively. The difference between propionic and butyric acid (mmol/l) had the best diagnostic properties, the area under the Receiver Operating Characteristic curve was 0.89 (95 % CI: 0.80–0.98) (p < 0.001). With a cut-off value > 0.015 mmol/l indicating IBS, the sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio were 92 %, 72 %, 3.29, 0.11 and 29.6 respectively. Similar diagnostic properties were shown for all the IBS subgroups.
Conclusions
The study indicated that faecal SCFA could be a non-invasive, valid and reliable biomarker for the differentiation of healthy subjects from subjects with IBS.
doi:10.1186/s12876-016-0446-z
PMCID: PMC4847229  PMID: 27121286
2.  Evaluation of dose-efficacy of sorafenib and effect of transarterial chemoembolization in hepatocellular carcinoma patients: a retrospective study 
BMC Gastroenterology  2016;16:50.
Background
Transarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively. High costs with adverse events (AE) of sorafenib might limit sorafenib dosage, further affecting therapeutic response. To attain greatest benefit, we evaluated the efficacy of different doses and effect of TACE during and after sorafenib discontinuation in patients representing Child-Pugh Classification Class A with venous or extra-hepatic invasion.
Methods
A total 156 patients met the criteria and were divided into Groups I (n = 52) accepting 800 mg/day; II (n = 58) accepting 800 mg/day and reduced to 400 mg/day owing to AE; and III (n = 46) accepting 400 mg/day. TACE was performed during and after sorafenib discontinuation and therapeutic response bimonthly to four-monthly was rated thereafter.
Results
Median duration of sorafenib treatment and patients’ survival were 4.00 ± 0.45 and 7.50 ± 1.44 months in all cases; 2.50 ± 0.90 and 5.00 ± 1.10 months in Group I; 5.50 ± 1.27 and 16.50 ± 1.86 months in Group II; 4.00 ± 0.94 and 6.50 ± 2.49 months in Group III. Group II presented the best response and survival benefit (p = 0.010 and p = 0.011 respectively). Child-Pugh Classification score 5 (Hazard Ratio = 0.492, p = 0.049), absent AE (3.423, p = 0.015), tumor numbers ≤ 3 (0.313, p = 0.009), sorafenib duration ≤ 1 cycle (3.694, p = 0.004), and absent TACE (3.197, p = 0.008) significantly correlated with patient survival. TACE benefit appeared in separate and total cases during (p = 0.002, p = 0.595, p = 0.074, p = 0.002 respectively) and after discontinuation of sorafenib administration (p = 0.001, p = 0.034, p = 0.647, p = 0.001 respectively).
Conclusions
Low-dosage sorafenib not only appeared tolerable and lowered economic pressure but also provided satisfactory results. TACE benefited patient’s survival during and after sorafenib discontinuation.
doi:10.1186/s12876-016-0464-x
PMCID: PMC4847248  PMID: 27117280
Dose-efficacy; Sorafenib; TACE; Hepatocellular carcinoma patient
3.  Determination of the appropriate propofol infusion rate for outpatient upper gastrointestinal endoscopy-a randomized prospective study 
BMC Gastroenterology  2016;16:49.
Background
Pain and discomfort related to endoscopy sessions can be alleviated by sedation, which minimizes anxiety and allows safe examination. For outpatient endoscopy, reliable short-term sedation without secondary effects is required. This study aimed to assess the effects of intravenous propofol rates on sedation in outpatients undergoing upper gastrointestinal endoscopy.
Methods
This randomized prospective study evaluated 300 outpatients submitted to upper gastrointestinal endoscopy. Patients received propofol at 500, 1000 or 2000 ml/h. The primary outcome assessed was hypoxemia incidence. In addition, time to sedation and incidence of hypotension, deep sedation, extremity motor activity, cough, nausea, hiccough, and awareness were evaluated.
Results
Recovery time and incidence of hypoxemia, hypotension, and deep sedation were significantly increased in individuals treated at 2000 ml/h in comparison with values obtained for 500 and 1000 ml/h groups (P < 0.01). Compared with the 500 ml/h group, motor activity of the extremities, cough, nausea, hiccough, and awareness were significantly decreased and the mean scores for endoscopist’s and patients’ satisfaction were significantly increased in the 1000 and 2000 ml/h groups (P < 0.01).
Conclusion
Propofol infused at 1000 ml/h appeared to be the most suitable infusion rate for outpatient upper gastrointestinal endoscopy.
Trial registration
Registration number: ChiCTR-TRC-14004786; Registration date: 2014-06-04
doi:10.1186/s12876-016-0463-y
PMCID: PMC4845313  PMID: 27117223
Propofol; Outpatient; Upper gastrointestinal endoscopy; Sedation; Complications
4.  Fecal calprotectin level correlated with both endoscopic severity and disease extent in ulcerative colitis 
BMC Gastroenterology  2016;16:47.
Background
The relationship between fecal calprotectin (FC) and disease extent in ulcerative colitis (UC) has not been fully elucidated. The aim of this study was to clarify the correlation of FC with disease extent and severity in UC patients.
Methods
UC patients scheduled to undergo an ileocolonoscopy were enrolled and fecal samples for FC measurement were collected prior to the procedure. A Mayo endoscopic subscore (MES) was determined for each of 5 colonic segments. To evaluate the association of FC with extent of affected mucosa as well as disease severity, we assessed the correlation of FC level with the sum of MES (S-MES) for the 5 colonic segments as compared to the maximum score of MES (M-MES).
Results
FC measurements in conjunction with findings from 136 complete colonoscopies in 102 UC patients were evaluated. FC level showed a stronger correlation with S-MES (correlation coefficient r = 0.86, p < 0.001) as compared to M-MES (r = 0.79, p < 0.001). In patients with an M-MES of 1, 2, and 3, FC level showed a significant correlation with S-MES (r = 0.67, p < 0.001; r = 0.70, p < 0.001; r = 0.47, p = 0.04, respectively). Our findings indicate that FC level is elevated in patients with greater areas of affected mucosa even in those with the same M-MES value.
Conclusions
FC level was shown to be correlated with the extent of affected mucosa as well as severity in UC patients, thus it is useful for precise assessment of mucosal inflammation.
doi:10.1186/s12876-016-0462-z
PMCID: PMC4830074  PMID: 27071448
Ulcerative colitis; Fecal calprotectin; Disease extent
5.  Presenting symptoms predict local staging of anal cancer: a retrospective analysis of 86 patients 
BMC Gastroenterology  2016;16:46.
Background
Incidence of anal carcinoma (AC) is increasing and timely diagnosis is critical for efficient therapy. However, there is a paucity of recent studies addressing clinical symptoms and physical findings of anal carcinoma.
Methods
We performed a retrospective study reviewing history, symptoms and physical findings from 86 patients with newly diagnosed AC. We analyzed frequency of symptoms and physical findings according to T and TNM stage and their predictive value regarding tumor stage.
Results
Most patients presented with T2 (37 %) or T3 (29 %) cancer. 85 of 86 patients were symptomatic with anal bleeding (78 %), anal/perianal pain (63 %), weight loss (31 %) and foreign body sensation (22 %). 95 % of patients had ≥1 finding on physical examination including a visible tumor, palpable resistance and pain/blood during digital rectal examination. Patients with locally advanced disease (T3/T4) presented with more symptoms (p < 0.01) and more physical findings (p = 0.04) than patients with T1/T2 disease. On multivariate regression analysis perianal pain, painful defecation and weight loss were significantly associated with T3/T4 disease.
Conclusion
Clinical symptoms and physical findings are present in nearly all AC patients. Pain referred to the perianal region, painful defecation and weight loss have predictive value for locally advanced disease.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-016-0461-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-016-0461-0
PMCID: PMC4822238  PMID: 27048435
Anal carcinoma; Symptoms; Physical examination; Tumor staging
6.  Implementation of baby boomer hepatitis C screening and linking to care in gastroenterology practices: a multi-center pilot study 
BMC Gastroenterology  2016;16:45.
Background
Estimates suggest that only 20 % of HCV-infected patients have been identified and <10 % treated. However, baby boomers (1945-1965) are identified as having a higher prevalence of HCV which has led the Centers for Disease Control and Prevention to make screening recommendations. The aim of this study was to implement the CDC’s screening recommendations in the unique setting of gastroenterology practices in patients previously unscreened for HCV.
Methods
After obtaining patient informed consent, demographics, clinical and health-related quality of life (HRQOL) data were collected. A blood sample was screened for HCV antibody (HCV AB) using the OraQuick HCV Rapid Antibody Test. HCV AB-positive patients were tested for presence of HCV RNA and, if HCV RNA positive, patients underwent treatment discussions.
Results
We screened 2,000 individuals in 5 gastroenterology centers located close to large metropolitan areas on the East Coast (3 Northeast, 1 Mid-Atlantic and 1 Southeast). Of the screened population, 10 individuals (0.5 %) were HCV AB-positive. HCV RNA testing was performed in 90 % (9/10) of HCV AB-positive individuals. Of those, 44.4 % (4/9) were HCV RNA-positive, and all 4 (100 %) were linked to caregiver. Compared to HCV AB negative subjects, HCV AB-positive individuals tended to be black (20.0 vs. 5.2 %, p = 0.09) and reported significantly higher rates of depression: 60.0 vs. 21.5 %, p = 0.009. These individuals also reported a significantly lower HRQOL citing having more fatigue, poorer concentration, and a decreased level of energy (p < 0.05).
Discussion
Although the prevalence of HCV AB-positive was low in previously unscreened subjects screened in the gastroenterology centers, the linkage to care was very high. The sample of patients used in this study may be biased, so further studies are needed to assess the effectiveness of the CDC screening recommendations.
Conclusion
Implementation of the Baby Boomer Screening for HCV requires identifying screening environement with high prevalence of HCV+ individuals as well as an efficient process of linking them to care.
doi:10.1186/s12876-016-0438-z
PMCID: PMC4820944  PMID: 27044402
7.  Case report of hepatic artery dissection secondary to hepatic artery pseudoaneurysm after living donor liver transplantation 
BMC Gastroenterology  2016;16:44.
Background
Hepatic artery pseudoaneurysm (HAP) and Hepatic artery dissection are rare vascular complications after living donor liver transplantation (LDLT), which may lead to graft loss and death of the recipients. Conventional gray-scale and Doppler ultrasound, as well as contrast-enhanced ultrasound (CEUS), play important roles in identifying vascular complications in the early postoperative period and during follow-up. We report a case of hepatic artery dissection secondary to HAP after LDLT, which was diagnosed and followed for one year by ultrasound. To the best of our knowledge, few studies have reported similar cases after liver transplantation in the English literature.
Case presentation
A 43-year-old man underwent right-lobe LDLT for treatment of a severe acute hepatitis B infection and was followed up with ultrasound examinations for one year. Conventional gray-scale and Doppler ultrasound combined with contrast-enhanced ultrasound (CEUS) accurately revealed the occurrence of HA dissection secondary to HAP and accompanied by thrombosis and collateral circulation, as well as secondary biliary complications, which provided a prompt diagnosis and guidance for the treatment.
Conclusion
Our case suggests that ultrasound can help detect hepatic artery pseudoaneurysm and dissection, as well as secondary biliary lesions after LDLT in an accurate and timely manner and provide useful information for the treatment chosen. CEUS shows potential as an important complementary technique to gray-scale and Doppler ultrasound.
doi:10.1186/s12876-016-0458-8
PMCID: PMC4818394  PMID: 27036207
Hepatic artery pseudoaneurysm; Dissection; Living-donor liver transplantation; Ultrasound; Contrast-enhanced ultrasound
8.  Role of preoperative biliary stents, bile contamination and antibiotic prophylaxis in surgical site infections after pancreaticoduodenectomy 
BMC Gastroenterology  2016;16:43.
Background
The routine use of preoperative biliary drainage before pancreaticoduodenectomy (PD) remains controversial. This observational retrospective study compared stented and non-stented patients undergoing PD to assess any differences in post-operative morbidity and mortality.
Methods
A total of 180 consecutive patients who underwent PD and had intra-operative bile cultures performed between January 2010 and February 2013 were retrospectively identified. All patients received peri-operative intravenous antibiotic prophylaxis, primarily cefazolin.
Results
Overall incidence of post-operative surgical complications was 52.3 %, with no difference between stented and non-stented patients (53.4 % vs. 51.1 %; p = 0.875). However, stented patients had a significantly higher incidence of deep incisional surgical site infections (SSIs) (p = 0.038). In multivariate analysis, biliary stenting was confirmed as a risk factor for deep incisional SSIs (p = 0.044). Significant associations were also observed for cardiac disease (p = 0.010) and BMI ≥25 kg/m2 (p = 0.045). Enterococcus spp. were the most frequent bacterial isolates in bile (74.5 %) and in drain fluid (69.1 %). In antimicrobial susceptibilty testing, all Enterococci isolates were cefazolin-resistant.
Conclusion
Given the increased risk of deep incisional SSIs, preoperative biliary stenting in patients underging PD should be used only in selected patients. In stented patients, an antibiotic with anti-enterococcal activity should be chosen for PD prophylaxis.
doi:10.1186/s12876-016-0460-1
PMCID: PMC4815172  PMID: 27036376
Stent; Pancreaticoduodenectomy; Surgical site infection; Enterococcus spp
9.  Comparison of the effectiveness of polyethylene glycol with and without electrolytes in constipation: a systematic review and network meta-analysis 
BMC Gastroenterology  2016;16:42.
Background
Polyethylene glycol is commonly used to manage constipation and is available with or without electrolytes. The addition of electrolytes dates back to its initial development as lavage solutions in preparation for gastrointestinal interventions. The clinical utility of the addition of electrolytes to polyethylene glycol for the management of constipation is not established.
The objective of this systematic review and network meta-analysis (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG + E) or without electrolytes (PEG) in the management of functional constipation in adults.
Methods
A systematic review was conducted to identify randomised controlled clinical trials that assessed the use of polyethylene glycol in functional constipation. The primary outcome was the mean number of bowel movements per week.
Results
Nineteen studies were included in the NMA (PEG N = 9, PEG + E N = 8, PEG versus PEG + E N = 2; involving 2247 patients). PEG and PEG + E are both effective, increasing the number of bowel movements per week by 1.8 (95 % Crl 1.0, 2.8) and 1.9 (95 % Crl 0.9, 3.0) respectively versus placebo and by 1.8 (95 % Crl 0.0, 3.5) and 1.9 (95 % Crl 0.2, 3.6) respectively versus lactulose. There was no efficacy difference between PEG + E and PEG (0.1, 95 % Crl −1.1, 1.2) and there were no differences in safety or tolerability.
Conclusions
Polyethylene glycol with and without electrolytes are effective and safe treatments for constipation in adults. The addition of electrolytes to polyethylene glycol does not appear to offer any clinical benefits over polyethylene glycol alone in the management of constipation.
doi:10.1186/s12876-016-0457-9
PMCID: PMC4815254  PMID: 27029340
Systematic review; Meta-analysis; Constipation; Polyethylene glycol; Macrogol
10.  Synergistic effect of κ-carrageenan on oxazolone-induced inflammation in BALB/c mice 
BMC Gastroenterology  2016;16:41.
Background
Carrageenan is a traditional ingredient that has been widely used in the food industry. In the present study, we propose a hypothesis that carrageenan is a conditional inflammatory agent. When the intestinal tract is in an “unhealthy” state such as that during bacterial infection or acute inflammation, carrageenan can synergistically enhance the inflammatory response.
Methods
BALB/C mice received κ-carrageenan via intragastric administration prior to the induction of oxazolone colitis. Weight changes, survival rate, histologic change, secretion of inflammatory cytokines, ratio of regulatory T cells (Tregs) in peripheral blood, and expression of genes and proteins involved in inflammation and cell proliferation in the colonic mucosa were examined.
Results
Intragastric administration of κ-carrageenan to BALB/c mice prior to the induction of oxazolone colitis resulted in an aggravation of body weight loss, a decrease in the survival ratio, aggravation of colonic inflammation, and decrease in the ratio of CD4 + CD25+/CD4+. The secretion of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) also significantly increased after κ-carrageenan administration. κ-Carrageenan, together with oxazolone, suppressed the expression of forkhead box p3 (FOXp3) and increased the expression of Toll-like receptor 4 (TLR4), Nuclear factor-κB (NF-κB), and proliferating cell nuclear antigen in the colonic mucosa. These results were confirmed by qRT-PCR and western blot analyses at the molecular and protein levels, respectively.
Conclusions
κ-Carrageenan aggravated oxazolone-induced intestinal inflammation in BALB/c mice. This effect is associated with an activation of the TLR4-NF-κB pathway, a decreased ratio of Tregs, and the induction of Th2-dependent immune responses.
doi:10.1186/s12876-016-0459-7
PMCID: PMC4807553  PMID: 27015810
κ-carrageenan; Oxazolone; Intestinal inflammation; Aggravation
11.  Food IgG4 antibodies are elevated not only in children with wheat allergy but also in children with gastrointestinal diseases 
BMC Gastroenterology  2016;16:39.
Background
Food sIgG and sIgG4 are highly individually versatile. We put a hypothesis that one of the responsible factors is the presence of gastrointestinal inflammatory diseases. The objectives were: 1. An analysis of wheat and rice sIgG and sIgG4 in healthy children, children with IgE-mediated wheat allergy (WA), coeliac disease (CD) and Helicobacter pylori infection (HP). 2. Usability of wheat sIgG and sIgG4 in the WA diagnostics.
Methods
We compared 388 each wheat and rice sIgG and sIgG4 in a group of 200 children: 50 WA (diagnosis, diet treatment, tolerance), 50 CD (diagnosis and remission), 50 HP and 50 healthy. SIgE, sIgG, sIgG4 were determined with the FEIA method (Pharmacia CAP System).
Results
In healthy children food sIgG were the lowest; no sIgG4 were found. In the CD diagnosis group wheat and rice sIgG and rice sIgG4 were the most common and their concentrations were the highest (p < .001, p < .05). Wheat sIgG4 were the highest in WA children (diagnosis and tolerance) to fall during the elimination diet (p < .05). Wheat and rice sIgG remained the same in all allergy phases. Rice sIgG also did not differ in the class G4.
Conclusions
1. Serum concentrations of wheat and rice sIgG and sIgG4 are elevated in children with CD, HP and WA. 2. Sub-clinical incidence of some gastrointestinal inflammatory diseases may be responsible for high individual versatility of food sIgG and sIgG4 concentrations in serum. 3. Wheat sIgG and sIgG4 in children do not correlate with WA clinical picture.
doi:10.1186/s12876-016-0450-3
PMCID: PMC4802593  PMID: 27004959
Children; Coeliac disease; Helicobacter pylori infection; Specific IgG; Specific IgG4; Wheat allergy
12.  Off-treatment durability of antiviral response to nucleoside analogues in patients with chronic hepatitis B 
BMC Gastroenterology  2016;16:38.
Background
Off-treatment durability of nucleoside analogue (NA) therapy in patients with chronic hepatitis B has not been well investigated. In this study we monitored antiviral effect of NA therapy and evaluated off-treatment durability after NA cessation in patients with chronic hepatitis B.
Patients and methods
A total of 94 consecutive patients (39 HBeAg-negative and 55 HBeAg-positive patients) who received NA therapy were followed up for approximately 9 years. We discontinued NA according to the following criteria; undetectable serum HBV-DNA by polymerase chain reaction (PCR) on three separate occasions at least 6 months apart in HBeAg-negative patients (APASL stopping recommendation), and seroconversion from HBeAg-positive to HBeAb-positive and undetectable serum HBV-DNA by PCR for at least 12 months in HBeAg-positive patients.
Results
The cumulative rate of relapse after NA cessation was 48 % and 40 % in HBeAg-negative and -positive patients, respectively. Higher baseline serum alanine aminotransferase level was the only significant predictor for maintaining remission. No patients experienced decompensation after relapse. HBsAg loss occurred at an annual rate of 1.4 % and 0.4 % in HBeAg-negative and -positive patients, respectively. Hepatocellular carcinoma developed at an annual rate of 0.6 % in both HBeAg-negative and -positive patients.
Conclusions
Almost half of the patients did not relapse after cessation of NA therapy in both HBeAg-negative and -positive patients. Therefore, NA therapy could be discontinued with close monitoring if the APASL stopping recommendation is satisfied even in HBeAg-negative patients.
doi:10.1186/s12876-016-0454-z
PMCID: PMC4794926  PMID: 26987437
Chronic hepatitis B; Nucleoside analogue; Durability; Hepatocellular carcinoma; HBs antigen
13.  Prevalence of gastro-esophageal reflux disease and its risk factors in a community-based population in southern India 
BMC Gastroenterology  2016;16:36.
Background
The prevalence of gastro-esophageal reflux disease (GERD) varies widely around the world. This study aimed to investigate the prevalence and risk factors of GERD in a general population of southern India.
Methods
An interview-based observational study was carried out in southern India during 2010 and early 2011 using a GERD questionnaire (GerdQ). In total 1072 participants were enrolled using a multi-stage cluster sampling method. Presence of GERD was defined as a score of ≥ 8. Logistic regression models were used to derive odds ratios (ORs) with 95 % confidence intervals (CIs).
Results
The prevalence of GERD was 22.2 % (238/1072) in southern India, and was more common among older subjects and men. Overweight and obese subjects had a dose-dependent increased risk of GERD, compared to those with body mass index less than 25 (multivariate-adjusted OR = 1.4, 95 % CI 1.0–2.0; OR = 2.3, 95 % CI 1.3–4.1, respectively). People residing in urban community were more vulnerable to GERD than those in rural community (multivariate-adjusted OR = 1.8, 95 % CI 1.3–2.5). Similarly, those with a lower educational level appeared to have an increased risk of GERD. Further, those with a habit of pan masala chewing were more likely to develop GERD compared with those abstained from the habit (multivariate-adjusted OR = 2.0, 95 % CI 1.2–3.2).
Conclusions
GERD is highly prevalent in southern India. Increasing age and BMI, an urban environment, lower educational level, and pan masala chewing appear to be risk factors of GERD symptoms for the studied population.
doi:10.1186/s12876-016-0452-1
PMCID: PMC4791779  PMID: 26979399
Gastro-esophageal reflux disease; Questionnaire; Prevalence; Risk factors
14.  Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10 years and under: retrospective cohort study from two tertiary centres in the United Kingdom and in Italy 
BMC Gastroenterology  2016;16:35.
Background
Most children with Inflammatory Bowel Disease (IBD) are diagnosed between 11 and 16 years of age, commonly presenting with features of typical IBD. Children with onset of gut inflammation under 5 years of age often have a different underlying pathophysiology, one that is genetically and phenotypically distinct from other children with IBD. We therefore set out to assess whether children diagnosed after the age of 5 years, but before the age of 11, have a different clinical presentation and outcome when compared to those presenting later.
Methods
Retrospective cohort study conducted at two European Paediatric Gastroenterology Units. Two cohorts of children with IBD (total number = 160) were compared: 80 children diagnosed between 5 and 10 years (Group A), versus 80 children diagnosed between 11 and 16 (Group B). Statistical analysis included multiple logistic regression.
Results
Group A presented with a greater disease activity (p = 0.05 for Crohn’s disease (CD), p = 0.03 for Ulcerative Colitis (UC); Odds Ratio 1.09, 95 % Confidence Interval: 1.02–1.1), and disease extent (L2 location more frequent amongst Group A children with CD (p = 0.05)). No significant differences were observed between age groups in terms of gastro-intestinal and extra-intestinal signs and symptoms at disease presentation, nor was there a difference in the number of hospitalisations due to relapsing IBD during follow-up. However, children in Group A were treated earlier with immunosuppressants and had more frequent endoscopic assessments.
Conclusion
While clinicians feel children between 5 and 10 years of age have a more severe disease course than adolescents, our analysis also suggests a greater disease burden in this age group. Nevertheless, randomized trials to document longer-term clinical outcomes are urgently needed, in order to address the question whether a younger age at disease onset should prompt per se a more “aggressive” treatment. We speculate that non-clinical factors (e.g. genetics, epigenetics) may have more potential to predict longer term outcome than simple clinical measures such as age at diagnosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-016-0455-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-016-0455-y
PMCID: PMC4791934  PMID: 26976427
Inflammatory Bowel Disease (IBD); Age; Children; Presentation; Location; Severity; Outcomes
15.  Comparative experimental investigation on the efficacy of mono- and multiprobiotic strains in non-alcoholic fatty liver disease prevention 
BMC Gastroenterology  2016;16:34.
Background
To investigate the efficacy of different probiotic strains, their combinations and forms (alive or lyophilized) in nonalcoholic fatty liver disease (NAFLD) prevention.
Methods
In this study, 70 rats have been used divided into 7 groups of 10 animals in each: I – intact rats, II-VII – rats with monosodium glutamate (MSG)-induced NAFLD. Rats with NAFLD were untreated (group II, MSG-obesity group) and treated with probiotics (groups III–VII). In order to develop NAFLD, newborn rats of groups II–VII were injected with a solution of monosodium glutamate (MSG) (4 mg/g) subcutaneously (s.c.) at 2nd,4th, 6th, 8th,10th postnatal day. The groups III–V received lyophilized monoprobiotics B. animalis VKL, B. animalis VKB, L.casei IMVB-7280, respectively. The group VI received 2.5 ml/kg of an aqueous solution of a mixture of the three probiotic strains (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB) at a dose of 50 mg/kg (5 × 109 CFU/kg) (g) (intragastrically). The group VII was treated with multiprobiotic “Symbiter” containing biomass of 14 alive probiotic strains (Lactobacillus + Lactococcus (6 × 1010 CFU/g), Bifidobacterium (1 × 1010/g), Propionibacterium (3 × 1010/g), Acetobacter (1 × 106/g)) at a dose of 140 mg/kg (1.4 × 1010 CFU/kg). The treatment with probiotics was started at the age of 1 month. There were 3 courses of treatment, each included 2-week administration and 2-week break. All parameters were measured in 4-month aged rats.
Results
Introduction of MSG during the neonatal period leads to the NAFLD development in the 4-months old rats. For steatosis degree there was no significant difference between MSG-obesity group and lyophilized monocomponent probiotics groups (III–V). The highest manifestation of steatosis was observed for B. animalis VKL group (2.0 ± 0.25) as compared to B. animalis VKB (1.70 ± 0.21) and L. casei IMVB-7280 (1.80 ± 0.20). The steatosis score changes between all monoprobiotics groups (III–V) were insignificant. Administration from birth of both alive (VII) and lyophilized (VI) probiotic mixture lead to a significant decrease by 69.5 % (p < 0.001) and 43.5 % (p < 0.025) of steatosis score respectively as compared to the MSG-obesity group (2.3 ± 0.21 %). For both alive and lyophilized probiotic mixtures, reduction of lobular inflammation was observed. These histological data were confirmed by the significant decrease of total lipids and triglycerides content in the liver approximately by 22–25 % in groups treated with probiotic mixtures (VI, VII) compared to the MSG-obesity group.
Conclusion
We established failure of NAFLD prevention with lyophilized monoprobiotic strains and the efficacy of probiotic mixture with the preference of alive probiotic strains.
doi:10.1186/s12876-016-0451-2
PMCID: PMC4791938  PMID: 26976285
NAFLD; Prevention; Obesity; Lyophilized and alive probiotic strains; Monoprobiotic; Multistrain probiotics
16.  Evidence of surgical outcomes fluctuates over time: results from a cumulative meta-analysis of laparoscopic versus open appendectomy for acute appendicitis 
BMC Gastroenterology  2016;16:37.
Background
In surgical trials, complex variables such as equipment development and surgeons’ learning curve are involved. The evidence obtained in these trials can thus fluctuate over time. We explored the stability of the evidence obtained during surgery by conducting a cumulative meta-analysis of randomized controlled trials for open and laparoscopic appendectomy.
Methods
We conducted a cumulative meta-analysis of randomized controlled trials comparing laparoscopic appendectomy with open appendectomy for acute appendicitis, a topic with the greatest number of trials in the gastroenterological surgical field. We searched the MEDLINE (PubMed), EMBASE, and CINAHL databases up to September 2014 and reviewed the bibliographies. Outcomes were the incidence of intra-abdominal abscess, incidence of wound infection, operative time, and length of hospital stay. We used the 95 % confidence interval (95 % CI) of effect size for the significance test.
Results
Sixty-four trials were included in this analysis. Of the 51 trials addressing intra-abdominal abscesses, our cumulative meta-analysis of trials published up to and including 2001 demonstrated statistical significance in favor of open appendectomy (cumulative odds ratio [OR] 2.35, 95 % CI 1.30–4.25). The effect size in favor of open procedures began to disappear after 2001, leading to an insignificant result with an overall cumulative OR of 1.32 (95 % CI 0.84–2.10) when laparoscopic appendectomy was compared with open appendectomy.
Conclusions
The evidence regarding treatment effectiveness changed over time, after treatment effectiveness became significant in trials comparing laparoscopic and open appendectomy. Observing only the 95 % confidence interval of effect size from a meta-analysis may not provide conclusive results.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-016-0453-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-016-0453-0
PMCID: PMC4793521  PMID: 26979491
Cumulative meta-analysis; Randomized controlled trials; Laparoscopic appendectomy; Open appendectomy
17.  Acute cholangitis in an old patient with Crigler-Najjar syndrome type II - a case report 
BMC Gastroenterology  2016;16:33.
Background
Crigler-Najjar syndrome (CN) is a very rare genetic disorder characterized by an inability to conjugate bilirubin. Contrary to CN type I, patients with CN II exhibit residual capacity to conjugate bilirubin and may present a normal life expectancy.
Case presentation
We report an unusual late diagnosis of CN type II in an 80-year-old female admitted with severe acute cholangitis. While the patient present typical clinical and radiologic signs of bile duct obstruction and cholangitis, her blood analysis showed severe unconjugated hyperbilirubinemia. Endoscopic retrograde cholangiopancreatography confirmed the diagnosis and allowed therapeutic intervention. The anatomopathologic examination of her gallbladder following cholecystectomy showed signs of chronic cholecystitis.
Conclusion
The risk of gallstone disease may be increased in patients with CN syndrome. While unusual, we alert to this curious and potential life-threatening presentation.
doi:10.1186/s12876-016-0449-9
PMCID: PMC4788912  PMID: 26968162
Crigler Najjar; Hyperbilirubinemia; Acute cholangitis; Choledocolitiasis; Uridine diphosphate-glucuronosyl-transferase deficiency
18.  The prevalence of functional dyspepsia using Rome III questionnaire among chronic hepatitis C patients 
BMC Gastroenterology  2016;16:32.
Background
Hepatitis C virus (HCV) is a common chronic infection that is widely associated with symptoms of fatigue and abdominal pain. The aim of the present study was to determine the prevalence of functional dyspepsia (FD) among patients with hepatitis C.
Methods
This study included 252 patients with chronic hepatitis C and 150 healthy volunteers. Clinical and laboratory data were recorded for every patient. All patients and controls were administered a questionnaire of FD according to Rome III criteria.
Results
The percentage of patients with FD was significantly higher in patients with chronic HCV than normal controls (65.9 % vs 28.7 %, respectively). In chronic HCV patients, post prandial distention syndrome (PDS) subtype was the predominant type (86.1 %). The percentage of patients with a high fibrosis score (F2–3) and raised ALT were significantly higher in patients with FD than in patients without FD (P < 0.001; P < 0.04; respectively). A multivariate regression analysis revealed a significant association between fibrosis score, BMI and FD
Conclusion
FD is more prevalent in patients with chronic hepatitis C. Obese chronic HCV and those with higher fibrosis scores are more likely to have FD.
doi:10.1186/s12876-016-0443-2
PMCID: PMC4778305  PMID: 26940465
FD; Hepatitis C; PDS; Rome III
19.  Inoculation with enterococci does not affect colon inflammation in the multi-drug resistance 1a-deficient mouse model of IBD 
BMC Gastroenterology  2016;16:31.
Background
Intestinal bacteria are thought to play a role in the pathogenesis of human inflammatory bowel disease (IBD). We investigated whether oral inoculation with specific intestinal bacteria increased colon inflammation in the multi-drug resistance 1a-deficient (Mdr1a–/–) mouse model of IBD.
Methods
Five-week-old Mdr1a–/– mice (FVB background) and FVB mice were randomly assigned to one of two treatment groups (Control or Inoculation, n = 12 per group). All mice were fed AIN-76A rodent diet, and mice in the Inoculation groups also received a single oral bacterial inoculation consisting of twelve cultured Enterococcus species combined with conventional intestinal flora obtained from the gastrointestinal tract of healthy mice (EF.CIF). Body weight, food intake, and disease activity index (DAI) were assessed throughout the study, and at 21 or 24 weeks of age, inflammation was assessed post-mortem by determining colon length and histological injury score (HIS), and plasma serum amyloid A (SAA).
Results
Mdr1a–/– mice consumed more food than FVB mice at 13 weeks of age (P < 0.05). There was also a significant effect of genotype on body weight, with Mdr1a–/– mice weighing less than FVB mice throughout the study (P < 0.05) regardless of treatment, but there was no effect of inoculation on body weight (P > 0.25). Colon HIS of Mdr1a–/– mice was significantly higher than that of FVB mice in the Control (9.3 ± 4.7 (mean ± SD) vs. 0.58 ± 0.51; P < 0.001) and Inoculation (6.7 ± 5.1 vs. 0.92 ± 0.39; P < 0.001) groups. There was no difference in colon HIS of Mdr1a–/– mice in the Control group compared with Mdr1a–/– mice in the Inoculation group (P = 0.25), nor was there any difference in within-group variation of colon HIS in these two Mdr1a–/– groups. DAI was higher in Mdr1a–/– mice than in FVB mice, but there was no effect of treatment in either strain, nor were there any differences in colon length or plasma SAA.
Conclusions
Inoculation of Mdr1a–/– mice with the EF.CIF inoculum described here does not increase colon inflammation or reduce the observed variability of inflammation.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-016-0447-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-016-0447-y
PMCID: PMC4778357  PMID: 26940566
Colon; Multiple drug resistance; Enterococcus; Inflammatory bowel disease; Serum amyloid A protein
20.  Abdominal migraine in children: association between gastric motility parameters and clinical characteristics 
BMC Gastroenterology  2016;16:26.
Background
Approximately 0.2–1 % of children suffers from abdominal migraine (AM). Pathophysiology of AM has not been adequately studied. This study evaluated gastric motility in children with AM.
Methods
Seventeen children (6 boys), within an age range of 4–15 years, referred to a tertiary care paediatric unit, North Colombo Teaching Hospital Ragama, Sri Lanka, from 2007 to 2012, were screened. Those fulfilling Rome III criteria for AM were recruited after obtaining parental consent. None had clinical or laboratory evidence of organic disorders. Twenty healthy children (8 boys), with an age range of 4–14 years, were recruited as controls. Liquid gastric emptying rate (GE) and antral motility parameters were assessed using an ultrasound method.
Results
Average GE (41.6 % vs. 66.2 %, in controls), amplitude of antral contractions (A) (57.9 % vs. 89.0 %) and antral motility index (MI) (5.0 vs. 8.3) were lower and fasting antral area (1.8 cm2 vs. 0.6 cm2) was higher in children with AM (p < 0.01). No significant difference in the frequency of antral contractions (F) (8.8/3 min vs. 9.3/3 min, p = 0.08) was found between the two groups. Scores obtained for severity of abdominal pain had a negative correlation with A (r = −0.55, p = 0.03). Average duration of abdominal pain episodes correlated with GE (r = −0.58, p = 0.02). Negative correlations were observed between duration of AM and A (r = −0.55), F (r = −0.52), and MI (r = −0.57) (p < 0.05).
Conclusions
GE and antral motility parameters were significantly lower in children with AM. A significant correlation was found between symptoms and gastric motility. These findings suggest a possible role of abnormal gastric motility in the pathogenesis of AM.
doi:10.1186/s12876-016-0435-2
PMCID: PMC4770524  PMID: 26924750
Abdominal migraine; Abdominal pain; Functional gastrointestinal disorder; Gastric emptying; Gastrointestinal motility
21.  Does the intestinal microbial community of Korean Crohn’s disease patients differ from that of western patients? 
BMC Gastroenterology  2016;16:28.
Background
Intestinal microbiota play an important role in maintaining the homeostasis of the host immune system. To analyze the alteration of the intestinal microbial community structure in Korean Crohn’s disease (CD) patients, we performed a comparative metagenomic analysis between healthy people and CD patients using fecal samples and mucosal tissues of ileocecal valve.
Methods
16S rRNA genes from fecal samples or mucosal tissues of 35 CD patients and 15 healthy controls (HC) were amplified using a universal primer set and sequenced with GS FLX Titanium. The microbial composition and diversity of each sample were analyzed with the mothur pipeline, and the association between microbial community and clinical characteristics of the patients were investigated.
Results
The contribution of bacterial groups to the intestinal microbial composition differed between CD and HC, especially in fecal samples. Global structure and individual bacterial abundance of intestinal microbial community were different between feces and ileocecal tissues in HC. In CD patients with active stage, relative abundances of Gammaproteobacteria and Fusobacteria were higher in both fecal and mucosal tissue samples. Moreover, the intestinal microbial community structure was altered by anti-tumor necrosis factor (anti-TNF) treatment.
Conclusions
Our 16S rRNA sequence data demonstrate intestinal dysbiosis at the community level in Korean CD patients, which is similar to alterations of the intestinal microbial community seen in the western counterparts. Clinical disease activity and anti-TNF treatment might affect the intestinal microbial community structure in CD patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-016-0437-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-016-0437-0
PMCID: PMC4770608  PMID: 26922889
Crohn’s disease; Intestinal bacteria; Korean; Pyrosequencing; Dysbiosis
22.  Alcoholic vs non-alcoholic fatty liver in rats: distinct differences in endocytosis and vesicle trafficking despite similar pathology 
BMC Gastroenterology  2016;16:27.
Background
Non-alcoholic and alcoholic fatty liver disease (NAFLD and AFLD, respectively) are major health problems, as patients with either condition can progress to hepatitis, fibrosis, and cirrhosis. Although histologically similar, key differences likely exist in these two models. For example, altered content of several vesicle trafficking proteins have been identified in AFLD, but their content in NAFLD is unknown. In this study, we compared select parameters in NAFLD and AFLD in a rat model.
Methods
We fed either Lieber- DeCarli liquid control or alcohol-containing (35 % as calories) diet (AFLD model) or lean or high-fat (12 or 60 % derived from fat, respectively) pellets (NAFLD model) for 8–10 weeks, n = 8 in each model. Serum, hepatocytes and liver tissue were analyzed. Liver injury markers were measured in serum, triglyceride content and endocytosis (binding and internalization of 125I- asialoorosomucoid) was measured in isolated hepatocytes, and content of selected trafficking proteins (Rab3D, Rab7 and Rab18) were determined in whole liver tissue.
Results
Although liver injury markers and triglyceride content were similar in both models, binding and internalization of 125I- asialoorosomucoid was significantly impaired in the hepatocytes from AFLD, but not NAFLD, animals. In addition, protein content of the asialoglycoprotein receptor (ASGPR) and three trafficking proteins, Rab3D, Rab7and Rab18, were significantly decreased after alcohol, but not high-fat feeding. Levels of protein carbonylation, amount of glutathione stores, and lipid peroxidation were similar irrespective of the insult to the livers that resulted in fatty liver.
Conclusion
Impairments in protein trafficking in AFLD are likely a direct result of alcohol administration, and not a function of fatty liver.
doi:10.1186/s12876-016-0433-4
PMCID: PMC4770635  PMID: 26924554
Alcoholic fatty liver disease (AFLD); RabGTPase proteins; Asialoglycoprotein receptor (ASGPR); Receptor-mediated endocytosis; Non-alcohol fatty liver disease (NAFLD)
23.  Effect of coexisting diabetes mellitus and chronic kidney disease on mortality of cirrhotic patients with esophageal variceal bleeding 
BMC Gastroenterology  2016;16:29.
Background
Esophageal variceal bleeding (EVB) is a serious and common complication of cirrhosis. Diabetes mellitus (DM) and chronic kidney disease (CKD) increase mortality in patients with cirrhosis. However, whether coexisting DM and CKD increase mortality in cirrhotic patients with EVB remains unclear.
Methods
We enrolled cirrhotic patients hospitalized with the first presentation of EVB from 2005 through 2010 using Longitudinal Health Insurance Database 2005. The hazard ratios (HRs) of 42-day and one-year EVB mortality were calculated using Cox regression model.
Results
We identified 888 patients hospitalized with the first presentation of EVB. Among the cirrhotic patients with EVB, all-cause mortality at 42-day and one-year were 21.3 and 45.0 %, respectively. The respective HRs for the 42-day and one-year mortality were 1.80 (95 % confidence interval [CI], 1.10–2.97) and 1.52 (95 % CI, 1.06–2.17) for patients with CKD and 0.79 (95 % CI, 0.57–1.10) and 0.88 (95 % CI, 0.71–1.09) for patients with DM. Specifically, coexisting CKD and DM increased the 42-day and one-year mortality with respective HRs of 1.99 (95%CI, 1.03–3.84) and 1.84 (95%CI, 1.14–2.98) compared with those without CKD and DM. The HRs for 42-day and 1-year mortality in female patients with DM and CKD were 4.03 (95%CI, 1.40–11.59) and 2.84 (95%CI, 1.31–6.14) respectively, and were 2.93 (95%CI, 1.14–7.57) and 2.42 (95%CI, 1.28–4.57) in male patients with DM and CKD.
Conclusion
We identified that coexisting DM and CKD increased risk of mortality at 42 days and 1 year following EVB.
doi:10.1186/s12876-016-0434-3
PMCID: PMC4770691  PMID: 26924648
Chronic kidney disease; Cirrhosis; Diabetes mellitus; Esophageal variceal bleeding
24.  Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer 
BMC Gastroenterology  2016;16:30.
Background
Approximately 2.7 million Americans are chronically infected with hepatitis C virus (HCV). HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC). Increased oxidative stress is regarded as a major mechanism of HCV-related liver disease progression. Deficiencies in retinoid and carotenoid antioxidants may represent a major modifiable risk factor for disease progression. This study aims to identify key predictors of serum antioxidant levels in patients with HCV, to examine the relationship between retinoid/carotenoid concentrations in serum and hepatic tissue, to quantify the association between systemic measures of oxidative stress and antioxidant status, and to examine the relationship between retinoids and stellate cell activation.
Methods
Patients undergoing liver biopsy (n = 69) provided fasting blood, fresh tissue, urine and completed a diet history questionnaire. Serum and questionnaire data from healthy volunteers (n = 11), normal liver tissue from public repositories and patients without liver disease (n = 11) were also collected. Urinary isoprostanes, serum and tissue retinoid concentrations were obtained by UHPLC-MS-MS. Immunohistochemistry for αSMA was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between urinary isoprostanes, αSMA levels, and retinoids were assessed using Spearman correlation coefficients and non-parametric tests were utilized to test differences among disease severity groups.
Results
There was a significant inverse association between serum retinol, lycopene, and RBP4 concentrations with fibrosis stage. Serum β-carotene and lycopene were strongly associated with their respective tissue concentrations. There was a weak downward trend of tissue retinyl palmitate with increasing fibrosis stage. Tissue retinyl palmitate was inversely and significantly correlated with hepatic αSMA expression, a marker for hepatic stellate cell activation (r = −0.31, P < 0.02). Urinary isoprostanes levels were inversely correlated with serum retinol, β-carotene, and RBP4.
Conclusions
A decrease in serum retinol, β-carotene, and RBP4 is associated with early stage HCV. Retinoid and carotenoid levels decline as disease progresses, and our data suggest that this decline occurs early in the disease process, even before fibrosis is apparent. Measures of oxidative stress are associated with fibrosis stage and concurrent antioxidant depletion. Vitamin A loss is accompanied by stellate cell activation in hepatic tissue.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-016-0432-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-016-0432-5
PMCID: PMC4772305  PMID: 26927700
Vitamin A; HCV; Diet; Biomarker
25.  Case report: successful resection of a leiomyoma causing pseudoachalasia at the esophagogastric junction by tunnel endoscopy 
BMC Gastroenterology  2016;16:24.
Background
Pseudoachalasia is a rare disorder whose presentation strongly resembles idiopathic achalasia.
Case presentation
Here, we present a case of a 42-year-old female patient with esophageal leiomyoma who was initially diagnosed with achalasia. On endoscopical investigation, however, it became apparent that she had pseudoachalasia as consequence of a leiomyoma at the esophagogastric junction (EGJ). The condition was successfully treated through submucosal tunneling endoscopic resection.
Conclusion
This case suggests that submucosal tunneling endoscopic resection is a therapeutic u option for the treatment of pseudoachalasia caused by leiomyoma of EGJ.
doi:10.1186/s12876-016-0445-0
PMCID: PMC4766602  PMID: 26912038
Pseudoachalasia; Esophagogastric junction; Leiomyoma

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