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1.  The Clinical Correlations of Helicobacter pylori Virulence Factors and Chronic Spontaneous Urticaria 
Background and Study Aims. The association between Helicobacter pylori (H. pylori) and chronic spontaneous urticaria (CSU) remains controversial. This study explored the role of H. pylori in CSU among different virulent genotypes patients. Patients and Methods. Patients infected by H. pylori were sorted into two groups as group A (with CSU) and group B (without CSU). The tissue materials were taken via endoscopy for polymerase chain reaction study to determine virulence factors. After H. pylori eradication therapy, the eradication rate and response of urticaria were evaluated by using C13-UBT and a three-point scale (complete remission, partial remission, or no improvement). Results. The results were comparable between patients of groups A and B in terms of H. pylori infection rates and eradication rate. Longitudinal follow-up of 23.5 months showed complete remission of urticaria in 63.6% but no improvement in 36.4% of the patients after H. pylori eradication. H. pylori infected patients with different virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin gene A signal region and middle region have similar remission rates for CSU. Conclusions. Current study suggests that H. pylori may play a role in the development and disease course of CSU but may be irrelevant to different virulent genotypes.
PMCID: PMC3730156  PMID: 23956739
2.  Predicting the Progress of Caustic Injury to Complicated Gastric Outlet Obstruction and Esophageal Stricture, Using Modified Endoscopic Mucosal Injury Grading Scale 
BioMed Research International  2014;2014:919870.
Severe caustic injury to the gastrointestinal tract carries a high risk of luminal strictures. The aim of this retrospective study was to identify predicting factors for progress of caustic injury to gastric outlet obstruction (GOO) and esophageal strictures (ES), using modified endoscopic mucosal injury grading scale. We retrospectively reviewed medical records of patients with caustic injuries to the gastrointestinal tract in our hospital in the past 7 years. We enrolled 108 patients (49 male, 59 female, mean age 50.1 years, range 18–86) after applying strict exclusion criteria. All patients received early upper gastrointestinal endoscopy within 24 hours of ingestion. Grade III stomach injuries were found in 58 patients (53.7%); 43 (39.8%) esophageal, and 13 (12%) duodenal. Of the 108 patients, 10 (9.3%) died during the acute stage. Age over 60 years (OR 4.725, P = 0.029) was an independent risk factor of mortality for patients after corrosive injury. Among the 98 survivors, 36 developed luminal strictures (37.1%): ES in 18 patients (18.6%), GOO in 7 (7.2%), and both ES and GOO in 11 (11.3%). Grade III esophageal (OR 3.079, P = 0.039) or stomach (OR 18.972, P = 0.007) injuries were independent risk factors for obstructions. Age ≥60 years was the independent risk factor for mortality after corrosive injury of GI tract. Grade III injury of esophagus was the independent risk factor for development of ES. Grade III injury of stomach was the independent risk factor for development of GOO.
PMCID: PMC4137736  PMID: 25162035
3.  Decreased Gastric Motility in Type II Diabetic Patients 
BioMed Research International  2014;2014:894087.
Background. To differentiate gastric motility and sensation between type II diabetic patients and controls and explore different expressions of gastric motility peptides. Methods. Eleven type II diabetic patients and health volunteers of similar age and body mass index were invited. All underwent transabdominal ultrasound for gastric motility and visual analogue scales. Blood samples were taken for glucose and plasma peptides (ghrelin, motilin, and glucacon-like peptides-1) by ELISA method. Results. Gastric emptying was significantly slower in diabetic patients than controls (T50: 46.3 (28.0–52.3) min versus 20.8 (9.6–22.8) min, P ≤ 0.05) and less antral contractions in type II diabetic patients were observed (P = 0.02). Fundus dimensions did not differ. There were a trend for less changes in gastrointestinal sensations in type II diabetic patients especially abdomen fullness, hunger, and abdominal discomfort. Although the serum peptides between the two groups were similar a trend for less serum GLP-1in type II diabetic patients was observed (P = 0.098). Conclusion. Type II diabetic patients have delayed gastric emptying and less antral contractions than controls. The observation that there were lower serum GLP-1 in type II diabetic patients could offer a clue to suggest that delayed gastric emptying in diabetic patients is not mainly influenced by GLP-1.
PMCID: PMC4132491  PMID: 25147821
4.  Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues 
Quantification of hepatitis B surface antigen (HBsAg) has been suggested to be helpful in the management of chronic hepatitis B (CHB) patients. Nucleos(t)ide analogs (NAs) are the therapy of choice for CHB and are used in the majority of CHB patients. NAs are able to induce hepatitis B virus (HBV) viral suppression, normalization of alanine aminotransferase (ALT) levels, and improvement in liver histology. Automated quantitative assays for serum HBsAg have recently become available, facilitating standardized quantification of serum HBsAg. This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs. Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV, and can therefore be used to predict therapeutic response. NA treatment typically induces a less rapid decline in HBsAg than interferon treatment; it has been estimated that full HBsAg clearance can require decades of NA treatment. However, a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg. Currently, there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy. This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.
PMCID: PMC4069297  PMID: 24976706
Alanine aminotransferase; Hepatitis B virus; Hepatitis B surface antigen; Nucleos(t)ide analogs; Virological response
5.  Swab culture monitoring of automated endoscope reprocessors after high-level disinfection 
AIM: To conduct a bacterial culture study for monitoring decontamination of automated endoscope reprocessors (AERs) after high-level disinfection (HLD).
METHODS: From February 2006 to January 2011, authors conducted randomized consecutive sampling each month for 7 AERs. Authors collected a total of 420 swab cultures, including 300 cultures from 5 gastroscope AERs, and 120 cultures from 2 colonoscope AERs. Swab cultures were obtained from the residual water from the AERs after a full reprocessing cycle. Samples were cultured to test for aerobic bacteria, anaerobic bacteria, and mycobacterium tuberculosis.
RESULTS: The positive culture rate of the AERs was 2.0% (6/300) for gastroscope AERs and 0.8% (1/120) for colonoscope AERs. All the positive cultures, including 6 from gastroscope and 1 from colonoscope AERs, showed monofloral colonization. Of the gastroscope AER samples, 50% (3/6) were colonized by aerobic bacterial and 50% (3/6) by fungal contaminations.
CONCLUSION: A full reprocessing cycle of an AER with HLD is adequate for disinfection of the machine. Swab culture is a useful method for monitoring AER decontamination after each reprocessing cycle. Fungal contamination of AERs after reprocessing should also be kept in mind.
PMCID: PMC3325533  PMID: 22529696
Automated endoscope reprocessor; Gastrointestinal scope; High-level disinfection; Swab culture; Monitoring; Decontamination
6.  Effect of ginger on gastric motility and symptoms of functional dyspepsia 
AIM: To evaluate the effects of ginger on gastric motility and emptying, abdominal symptoms, and hormones that influence motility in dyspepsia.
METHODS: Eleven patients with functional dyspepsia were studied twice in a randomized double-blind manner. After an 8-h fast, the patients ingested three capsules that contained ginger (total 1.2 g) or placebo, followed after 1 h by 500 mL low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires, and blood was taken for measurement of plasma glucagon-like peptide-1 (GLP-1), motilin and ghrelin concentrations, at intervals throughout the study.
RESULTS: Gastric emptying was more rapid after ginger than placebo [median (range) half-emptying time 12.3 (8.5-17.0) min after ginger, 16.1 (8.3-22.6) min after placebo, P ≤ 0.05]. There was a trend for more antral contractions (P = 0.06), but fundus dimensions and gastrointestinal symptoms did not differ, nor did serum concentrations of GLP-1, motilin and ghrelin.
CONCLUSION: Ginger stimulated gastric emptying and antral contractions in patients with functional dyspepsia, but had no impact on gastrointestinal symptoms or gut peptides.
PMCID: PMC3016669  PMID: 21218090
Ginger (Zinger offinale); Functional dyspepsia; Gastric emptying; Antral contraction; Abdominal ultrasound; Ghrelin; Glucagon-like peptide-1; Motilin
7.  Predictors of rebleeding after initial hemostasis with epinephrine injection in high-risk ulcers 
AIM: To identify the predictors of rebleeding after initial hemostasis with epinephrine injection (EI) in patients with high-risk ulcers.
METHODS: Recent studies have revealed that endoscopic thermocoagulation, or clips alone or combined with EI are superior to EI alone to arrest ulcer bleeding. However, the reality is that EI monotherapy is still common in clinical practice. From October 2006 to April 2008, high-risk ulcer patients in whom hemorrhage was stopped after EI monotherapy were studied using clinical, laboratory and endoscopic variables. The patients were divided into 2 groups: sustained hemostasis and rebleeding.
RESULTS: A total of 175 patients (144, sustained hemostasis; 31, rebleeding) were enrolled. Univariate analysis revealed that older age (≥ 60 years), advanced American Society of Anesthesiology (ASA) status (category III, IV and V), shock, severe anemia (hemoglobin < 80 g/L), EI dose ≥ 12 mL and severe bleeding signs (SBS) including hematemesis or hematochezia were the factors which predicted rebleeding. However, only older age, severe anemia, high EI dose and SBS were independent predictors. Among 31 rebleeding patients, 10 (32.2%) underwent surgical hemostasis, 15 (48.4%) suffered from delayed hemostasis causing major complications and 13 (41.9%) died of these complications.
CONCLUSION: Endoscopic EI monotherapy in patients with high-risk ulcers should be avoided. Initial hemostasis with thermocoagulation, clips or additional hemostasis after EI is mandatory for such patients to ensure better hemostatic status and to prevent subsequent rebleeding, surgery, morbidity and mortality.
PMCID: PMC2988244  PMID: 21086569
Epinephrine injection; High-risk ulcers; Initial hemostasis; Predictors; Rebleeding
8.  Pseudoachalasia in a patient after truncal vagotomy surgery successfully treated by subsequent pneumatic dilations 
Pseudoachalasia is a difficult condition for the clinician to differentiate from idiopathic achalasia even by manometry, radiological studies or endoscopy. Its etiology is usually associated with tumors. In most cases, the diagnosis is made after surgical explorations. The proposed pathogenesis of the disease is considered as mechanical obstruction of the distal esophagus or infiltration of the malignancy that affects the inhibitory neurons of the meyenteric plexus in the majority of cases. Surgery has been reported as a cause of pseudoachalasia. We report a 70-year-old man who suffered from deglutination disorder caused by pseudo-achalasia after truncal vagotomy. The patient was symptom-free after a nine-year follow-up and complete recovery of esophageal motility status from pseudoachalasia after pneumatic dilations. We also reviewed the literature of pseudoachalasia.
PMCID: PMC4087422  PMID: 16937515
Truncal vagotomy; Pseudo-achalasia; Deglutination disorder; Pneumatic dilations; Sustain reversed esophageal motility
9.  Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwanese 
AIM: To elucidate the prognostic role and relationship of three molecular markers such as tumor suppressor gene p53, proliferating cell nuclear antigen (PCNA) and Ki-67 in gastric stromal tumor.
METHODS: A total of 108 surgically resected gastric smooth muscle tumor specimens were collected from January 1987 to December 1999. Immunohistochemical studies were performed on the paraffin sections of 99 of 108 CD117-positive tumors with antibodies of p53, PCNA, and Ki-67. Immunoreactivity of three molecular markers was recorded by labeling index (LI, %) and was analyzed for clinicopathologic and survival correlation.
RESULTS: Of the 99 cases, immunostaining revealed that 52 patients (52.5%) had p53, and 37 patients (37.3%) had Ki-67 immunoreactivity (defined as >10% of LI). All patients (100%) had PCNA immunoreactivity ranging from 12% to 93% of LI, divided into high or low by median. Statistics revealed that LI of three markers positively correlate to each other (P<0.01) and to microscopic tumor mitotic counts (P <0.001). By combination, patients with ≥2 markers (positive or high) in tumors had early tumor recurrence (P <0.001) and unfavorable outcome (P <0.001). Univariate analysis indicated that patients with tumor size >5 cm (P = 0.003), tumor mitosis >5/50 HPF (P < 0.001), p53 immunoreactivity (P  = 0.001), Ki-67 immunoreactivity (P =0.026), high PCNA LI (P =0.015) and male gender (P =0.036) were six predictors for early disease recurrence. Subsequent multivariate analysis revealed that mitotic counts, tumor size, and p53 immunoreactivity were three independent prognostic factors for both disease free and overall survival of patients. By combination of three independent prognostic factors for grouping, we found higher tumor recurrence rate (P <0.001) and shorter survival (P <0.001) existed in groups with increasing factors.
CONCLUSION: We first provide the prognostic value and linkage of three molecular markers in GISTs. The combination of three factors (p53, tumor size, and tumor mitosis) provides a more powerful prediction of prognosis than any single factor does.
PMCID: PMC4066093  PMID: 16489674
Gastrointestinal stromal tumor; GIST; p53; PCNA; Ki-67; Prognosis
10.  Clinical characteristics and prognostic factors of splenic abscess: A review of 67 cases in a single medical center of Taiwan 
AIM: To analyze 67 cases of splenic abscess in a medical center of Taiwan during a period of 19 years.
METHODS: From January 1986 to December 2004, a total of 67 patients with splenic abscess were enrolled for the retrospective study. The clinical characteristics, underlying diseases, organism spectra, therapeutic methods, APACHE II scores, and mortality rates were analyzed.
RESULTS: There were 41 males and 26 females with the mean age of 54.1 ± 14.1 years. Multiple splenic abscesses (MSA) account for 28.4% and solitary splenic abscess in 71.6% of the patients. Twenty-six of sixty-seven patients (35.8%) had extrasplenic abscesses, with leading site of liver (34.6%). Microbiological cultures were positive in 58 patients (86.6%), with 71.8% in blood culture and 93.5% in abscess culture. Gram negative bacillus (GNB) infection predominated (55.2%), with leading pathogen of Klebsiella pneumoniae (22.4%), followed by gram positive coccus (GPC) infection (31%). Splenectomy was performed in 26 patients (38.8%), percutaneous drainage or aspiration in 21 (31.3%), and antibiotic therapy alone in 20 patients (29.9%). Eventually, 12 of 67 patients expired (17.9 %). By statistics, spleen infected with GNB was likely to develop multiple abscesses compared with infection with GPC (P = 0.036). Patients with GNB infection (P = 0.009) and multiple abscesses (P = 0.011) experienced a higher mortality rate than patients with GPC infection and solitary abscess. The mean APACHE II score of 12 expired patients (16.3 ± 3.2) was significantly higher than that of the 55 survivals (7.2 ± 3.8) (P < 0.001).
CONCLUSION: MSA, GNB infection, and high APACHE II scores are poor prognostic factors. Early surgical intervention should be encouraged when these risk factors are present.
PMCID: PMC4066069  PMID: 16489650
Splenic abscess; Prognosis; Gram negative bacillus infection; APACHE II scores
11.  Neutrophil-to-Lymphocyte Ratio as a Predictor of Response to Peginterferon plus Ribavirin Therapy for Chronic Hepatitis C 
Disease Markers  2014;2014:462958.
We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n = 263; genotype 2, n = 297; others/unknown, n = 42) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved in 436 (73%) and 458 (76%) of the patients, respectively. Higher NLR (≥1.42) was found to be associated with higher prevalence of DM (P = 0.039) and higher hepatitis C viral load (P = 0.002) and white cell count (P < 0.001). NLR was significantly lower in patients with RVR and SVR compared to those without (P = 0.032 and 0.034, resp.). However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42) (odds ratio, 0.494, P = 0.038) was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2.
PMCID: PMC4255057  PMID: 25505815
12.  The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication 
PLoS ONE  2014;9(8):e105822.
Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study suggests that tailored levofloxacin-containing therapy should be administered only for patients with susceptible strains because it can achieve >90% success rates.
PMCID: PMC4139398  PMID: 25141137
13.  Outcome of Holiday and Nonholiday Admission Patients with Acute Peptic Ulcer Bleeding: A Real-World Report from Southern Taiwan 
BioMed Research International  2014;2014:906531.
Background. Recent findings suggest that patients admitted on the weekend with peptic ulcer bleeding might be at increased risk of adverse outcomes. However, other reports found that there was no “holiday effect.” The purpose of this study was to determine if these findings hold true for a real-life Taiwanese medical gastroenterology practice. Materials and Methods. We reviewed the medical files of hospital admissions for patients with peptic ulcer bleeding who received initial endoscopic hemostasis between January 2009 and March 2011. A total of 744 patients were enrolled (nonholiday group, n = 615; holiday group, n = 129) after applying strict exclusion criteria. Holidays were defined as weekends and national holidays in Taiwan. Results. Our results showed that there was no significant difference in baseline characteristics between the two groups. We also observed that, compared to the nonholiday group, patients in the holiday group received earlier endoscopy treatment (12.20 hours versus 16.68 hours, P = 0.005), needed less transfused blood (4.8 units versus 6.6 units, P = 0.02), shifted from intravenous to oral proton-pump inhibitors (PPIs) more quickly (5.3 days versus 6.9 days, P = 0.05), and had shorter hospital stays (13.05 days versus 17.36 days, P = 0.005). In the holiday and nonholiday groups, the rebleeding rates were 17.8% and 23.41% (P = 0.167), the mortality rates were 11.63% versus 13.66% (P = 0.537), and surgery was required in 2.11% versus 4.66% (P = 0.093), respectively. Conclusions. Patients who presented with peptic ulcer bleeding on holidays did not experience delayed endoscopy or increased adverse outcomes. In fact, patients who received endoscopic hemostasis on the holiday had shorter waiting times, needed less transfused blood, switched to oral PPIs quicker, and experienced shorter hospital stays.
PMCID: PMC4100444  PMID: 25093189
14.  Significance of Vitamin D Receptor Gene Polymorphisms for Risk of Hepatocellular Carcinoma in Chronic Hepatitis C 
Translational Oncology  2014;7(4):503-507.
Biological and epidemiological data suggest that vitamin D levels may influence cancer development. Several single nucleotide polymorphisms have been described in the vitamin D receptor (VDR) gene in association with cancer risk. We aimed to investigate the association of VDR gene polymorphisms with hepatocellular carcinoma (HCC) development in chronic hepatitis C patients.
In a cross-sectional, hospital-based setting, 340 patients (201 chronic hepatitis, 47 cirrhosis and 92 HCC) and 100 healthy controls receiving VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 C and TaqI rs731236 A) were enrolled.
Patients with HCC had a higher frequency of ApaI CC genotype (P = 0.027) and bAt[CCA]-haplotype (P = 0.037) as compared to control subjects. There were no differences in BsmI and TaqI polymorphisms between two groups. In patients with chronic hepatitis C, HCC subjects had a higher frequency of ApaI CC genotype and bAt[CCA]-haplotype than those with chronic hepatitis (P = 0.001 and 0.002, respectively) and cirrhosis (P = 0.019 and 0.026, respectively). After adjusting age and sex, logistic regression analysis showed that ApaI CC genotype (odds ratio: 3.02, 95% confident interval: 1.65-5.51) was independently associated with HCC development.
VDR ApaI polymorphism plays a role in the development of HCC among chronic hepatitis C patients. Further explorations of this finding and its implications are required.
PMCID: PMC4202781  PMID: 24894441
15.  The Influential Roles of Antibiotics Prophylaxis in Cirrhotic Patients with Peptic Ulcer Bleeding after Initial Endoscopic Treatments 
PLoS ONE  2014;9(5):e96394.
The influential roles of antibiotic prophylaxis on cirrhotic patients with peptic ulcer bleeding are still not well documented. The purpose of this study is to clarify these influential roles and to identify the risk factors associated with rebleeding, bacterial infection and in-hospital mortality. A cross-sectional, chart review study was conducted on 210 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients were divided into group A (with prophylactic intravenous ceftriaxone, n = 74) and group B (without antibiotics, n = 136). The outcomes were length of hospital days, prevention of infection, rebleeding rate and in-hospital mortality. Our results showed that more patients suffered from rebleeding and infection in group B than group A (31.6% vs. 5.4%; p<0.001 and 25% vs. 10.8%; p = 0.014 respectively). The risk factors for rebleeding were active alcoholism, unit of blood transfusion, Rockall score, model for end-stage liver disease score and antibiotic prophylaxis. The risk factors for infection were active alcoholism, Child-Pugh C, Rockall score and antibiotic prophylaxis. Rockall score was the predictive factor for in-hospital mortality. In conclusions, antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and rebleeding rate but not in-hospital mortality. Rockall score was the predictive factor of in-hospital mortality.
PMCID: PMC4008578  PMID: 24788341
16.  MicroRNAs in Hepatocellular Carcinoma: Carcinogenesis, Progression, and Therapeutic Target 
BioMed Research International  2014;2014:486407.
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer, with dismal outcomes and an increasing incidence worldwide. Hepatocarcinogenesis is a multistep process that progresses from chronic hepatitis through cirrhosis and/or dysplastic nodule to HCC. However, the detailed molecular pathogenesis remains unclear. MicroRNAs (miRNAs), small noncoding RNAs that regulate the translation of many genes, have emerged as key factors involved in several biological processes, including development, differentiation, and cell proliferation. Recent studies have uncovered the contribution of miRNAs to the cancer pathogenesis, as they can behave as oncogenes or tumor suppressor genes. In addition, other studies have demonstrated their potential values in the clinical management of HCC patients as some miRNAs may be used as prognostic or diagnostic markers. In this review, we summarize current knowledge about the roles of miRNAs in carcinogenesis and progression of HCC. We also discuss the potential application of miRNAs as diagnostic biomarkers and their potential roles in the intervention of HCC.
PMCID: PMC3996893  PMID: 24800233
17.  Ten-Day versus 14-Day Levofloxacin-Containing Triple Therapy for Second-Line Anti-Helicobacter pylori Eradication in Taiwan 
Second-line Helicobacter pylori (H. pylori) eradication with fluoroquinolone-containing triple therapy is one of the recommended treatment options, but neither 7-day nor 10-day regimens provide >90% success rates. The current retrospective study aimed to clarify the effects of 10-day and 14-day levofloxacin-containing triple therapies for second-line H. pylori eradication in a Taiwanese cohort and to evaluate the potential clinical factors influencing eradication. A total of 200 patients who failed H. pylori eradication using the standard triple therapy were prescribed with either a 10-day (EAL-10) or a 14-day (EAL-14) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily). Follow-up studies to assess treatment response were carried out 8 weeks later. Eradication rates attained by EAL-10 and EAL-14 were 75.6%; 95% CI = 63.9–85.3% and 92.5%; 95% CI = 84.5–98.1%, P = 0.002 in the per protocol analysis and 68%; 95% CI = 56.6–78.5% and 86%; 95% CI = 76.8–93.4%, P = 0.002 in the intention-to-treat analysis. The duration of H. pylori therapy is the independent risk factor of H. pylori eradication (P = 0.003). In conclusion, 14-day levofloxacin-containing triple therapy can provide a >90% H. pylori eradication rate, but 10-day treatment duration may be suboptimal. The longer duration of H. pylori therapy (14 days) is the independent risk factor.
PMCID: PMC3819765  PMID: 24235968
18.  The effects of endoscopic-guided balloon dilations in esophageal and gastric strictures caused by corrosive injuries 
BMC Gastroenterology  2013;13:99.
Esophageal stricture (ES) and gastric outlet obstruction (GOO) can occurred in patients injured by the ingestion of corrosive agents. These complications may occur concurrently but has not been reported in the literature. The aims of this study are to assess the effects and complications of endoscopic-guided balloon dilations (EBD) in patients with corrosive-induced upper gastrointestinal strictures, either ES or GOO alone and simultaneous occurrences of both (ES + GOO).
From July 2002 to December 2009, 36 patients with corrosive-induced upper gastrointestinal strictures in a tertiary hospital were recruited into this study. The patients were divided into three groups, ES group (n = 18), GOO (n = 7), and ES + GOO group (n = 11). All strictures were dilated under direct visualization by using through-the-scope balloon catheters to the end point of 15 mm. The end-point of treatment was successful ingestion of a solid or semisolid diet without additional dilation for more than 12 months.
These 36 patients included 15 males and 21 females with average age of 47 years ranging from 25 to 79 years. The success rates for ES group is significantly better than GOO and ES + GOO group (83.3% vs. 57.1% vs. 36.4% p = 0.035). Less complications were observed in ES group than in GOO and ES + GOO group (16.7% vs. 42.9% vs. 36.4%, p = 0.041). GOO group needed more sessions of dilations in order to achieve success dilations than ES and GOO groups (13.7 ± 4.9 vs. 6.1 ± 4.7 vs. 5.5 ± 2.1, p = 0.011).
Corrosive injuries complicated with ES can be effectively and safely treated by EBD. However, the success rates declined significantly in patients with GOO with or without ES and amore complications occurred.
PMCID: PMC3698201  PMID: 23758711
Esophageal stricture; Gastric outlet obstruction; Corrosives; Balloon dilation
19.  Surveillance cultures of samples obtained from biopsy channels and automated endoscope reprocessors after high-level disinfection of gastrointestinal endoscopes 
BMC Gastroenterology  2012;12:120.
The instrument channels of gastrointestinal (GI) endoscopes may be heavily contaminated with bacteria even after high-level disinfection (HLD). The British Society of Gastroenterology guidelines emphasize the benefits of manually brushing endoscope channels and using automated endoscope reprocessors (AERs) for disinfecting endoscopes. In this study, we aimed to assess the effectiveness of decontamination using reprocessors after HLD by comparing the cultured samples obtained from biopsy channels (BCs) of GI endoscopes and the internal surfaces of AERs.
We conducted a 5-year prospective study. Every month random consecutive sampling was carried out after a complete reprocessing cycle; 420 rinse and swabs samples were collected from BCs and internal surface of AERs, respectively. Of the 420 rinse samples collected from the BC of the GI endoscopes, 300 were obtained from the BCs of gastroscopes and 120 from BCs of colonoscopes. Samples were collected by flushing the BCs with sterile distilled water, and swabbing the residual water from the AERs after reprocessing. These samples were cultured to detect the presence of aerobic and anaerobic bacteria and mycobacteria.
The number of culture-positive samples obtained from BCs (13.6%, 57/420) was significantly higher than that obtained from AERs (1.7%, 7/420). In addition, the number of culture-positive samples obtained from the BCs of gastroscopes (10.7%, 32/300) and colonoscopes (20.8%, 25/120) were significantly higher than that obtained from AER reprocess to gastroscopes (2.0%, 6/300) and AER reprocess to colonoscopes (0.8%, 1/120).
Culturing rinse samples obtained from BCs provides a better indication of the effectiveness of the decontamination of GI endoscopes after HLD than culturing the swab samples obtained from the inner surfaces of AERs as the swab samples only indicate whether the AERs are free from microbial contamination or not.
PMCID: PMC3482587  PMID: 22943739
Surveillance culture monitoring; Gastrointestinal scope; Automated endoscope reprocessor; High-level disinfection reprocessing
20.  Comparative Study of Esophageal Stent and Feeding Gastrostomy/Jejunostomy for Tracheoesophageal Fistula Caused by Esophageal Squamous Cell Carcinoma 
PLoS ONE  2012;7(8):e42766.
A malignant tracheoesophageal/bronchoesophageal fistula (TEF) is a life-threatening complication of esophageal squamous cell carcinoma. A feeding gastrostomy/jejunostomy had been the most common treatment method for patients with TEF before the era of stenting. The aim of this retrospective study is to compare the prognosis of esophageal squamous cell carcinoma patients with TEF treated with an esophageal metallic stent to those treated with a feeding gastrostomy/jejunostomy.
We retrospectively reviewed a total of 1011 patients with esophageal squamous cell carcinoma between 1996 and 2011 at Kaohsiung Chang Gung Memorial Hospital, and 86 patients with TEF (8.5%) were identified. The overall survival and other clinical data were compared between 30 patients treated with an esophageal metallic stent and 35 patients treated with a feeding gastrostomy/jejunostomy.
Among the 65 patients receiving either an esophageal metallic stent or a feeding gastrostomy/jejunostomy, univariate analysis showed that treatment modality with an esophageal metallic stent (P = 0.007) and radiotherapy treatment after fistula diagnosis (P = 0.04) were predictive of superior overall survival. In the multivariate comparison, treatment modality with an esophageal metallic stent (P = 0.026, odds ratio: 1.859) represented the independent predictive factor of superior overall survival. There were no significant differences between groups in mean decrease in serum albumin or mean body weight loss. Compared to the feeding gastrostomy/jejunostomy group, a significantly higher proportion of patients in the stenting group (53% versus 14%, P = 0.001) were able to receive chemotherapy within 30 days after fistula diagnosis, indicating better infection control in the stenting group.
Compared with a feeding gastrostomy/jejunostomy, an esophageal metallic stent significantly improves overall survival in patients with malignant TEF in our retrospective analysis. Esophageal metallic stent placement may be considered the first-line of treatment for patients with malignant TEF.
PMCID: PMC3418295  PMID: 22912737
21.  Comparison of argon plasma coagulation in management of upper gastrointestinal angiodysplasia and gastric antral vascular ectasia hemorrhage 
BMC Gastroenterology  2012;12:67.
Vascular ectasias, including gastric antral vascular ectasia (GAVE) and angiodysplasia, are increasingly recognized as important sources of gastrointestinal bleeding. This study investigated and compared the efficacies and outcomes of treatment of upper gastrointestinal (UGI) angiodysplasia and GAVE hemorrhage by endoscopic argon plasma coagulation (APC).
From January 2006 to December 2009, 46 patients diagnosed with upper GI bleeding caused by angiodysplasia or GAVE at a tertiary hospital were recruited into this study. They included 26 males and 20 females with an average age of 65.6 years (range, 45–90 years). All patients underwent APC for hemostasis during an endoscopic procedure. Parameters such as underlying co-morbidities, number of endoscopic treatment sessions, recurrent bleeding, and clinical outcomes during follow-up were analyzed.
The 46 patients with UGI vascular ectasia hemorrhage included 27 patients with angiodysplasia and 19 with GAVE. The patients with angiodysplasia were older than those with GAVE (71.6 ± 10.2 years versus 61.8 ± 11.9 years, P = 0.005). More GAVE patients than angiodysplasia patients had co-existing liver cirrhosis (63.2% versus 25.9%, P = 0.012). The patients with GAVE had a higher rate of recurrent bleeding (78.9% versus 7.4%, P < 0.001) and required more treatment sessions to achieve complete hemostasis (2.4 ± 1.4 versus 1.1 ± 0.1, P < 0.001) than those with angiodysplasia. Univariate analysis demonstrated that age greater than 60 years (odds ratio (OR) = 8.929, P = 0.003), GAVE (OR = 0.021, P < 0.001), and previous radiation therapy (OR = 11.667, P = 0.032) were associated with higher rates of recurrent bleeding. Further multivariate analysis revealed that GAVE was the only independent risk factor for recurrent bleeding after APC treatment (OR = 0.027, P < 0.001).
Endoscopic hemostasis with APC is a safe treatment modality for both angiodysplasia and vascular ectasia bleeding. The efficacy of APC treatment is greater for angiodysplasia than for vascular ectasia bleeding. GAVE patients have a higher recurrent bleeding rate and may require multiple treatment sessions for sustained hemostasis.
PMCID: PMC3439282  PMID: 22681987
Endoscopic argon plasma coagulation; Angiodysplasia; Gastric antral vascular ectasia
22.  Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis 
BMC Gastroenterology  2012;12:28.
Many studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs.
Subjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27).
An initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group).
Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis.
PMCID: PMC3352107  PMID: 22455511
Intravenous proton-pump inhibitors; Peptic ulcer bleeding; Endoscopic hemostasis; Rebleeding; Rockall scores

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