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1.  High-level disinfection of gastrointestinal endoscope reprocessing 
High level disinfection (HLD) of the gastrointestinal (GI) endoscope is not simply a slogan, but rather is a form of experimental monitoring-based medicine. By definition, GI endoscopy is a semicritical medical device. Hence, such medical devices require major quality assurance for disinfection. And because many of these items are temperature sensitive, low-temperature chemical methods, such as liquid chemical germicide, must be used rather than steam sterilization. In summarizing guidelines for infection prevention and control for GI endoscopy, there are three important steps that must be highlighted: manual washing, HLD with automated endoscope reprocessor, and drying. Strict adherence to current guidelines is required because compared to any other medical device, the GI endoscope is associated with more outbreaks linked to inadequate cleaning or disinfecting during HLD. Both experimental evaluation on the surveillance bacterial cultures and in-use clinical results have shown that, the monitoring of the stringent processes to prevent and control infection is an essential component of the broader strategy to ensure the delivery of safe endoscopy services, because endoscope reprocessing is a multistep procedure involving numerous factors that can interfere with its efficacy. Based on our years of experience in the surveillance of culture monitoring of endoscopic reprocessing, we aim in this study to carefully describe what details require attention in the GI endoscopy disinfection and to share our experience so that patients can be provided with high quality and safe medical practices. Quality management encompasses all aspects of pre- and post-procedural care including the efficiency of the endoscopy unit and reprocessing area, as well as the endoscopic procedure itself.
PMCID: PMC4308530
Automated endoscope reprocessor; Bacterial culture; Gastrointestinal endoscopy; High-level disinfection; Liquid chemical germicide
2.  Diagnostic pitfall of sebaceous gland metaplasia of the esophagus 
We investigated the sebaceous gland metaplasia (SGM) of the esophagus and clarified the evidence of misdiagnosis and its diagnosis pitfall. Cases of pathologically proven SGM were enrolled in the clinical analysis and reviewed description of endoscope. In the current study, we demonstrated that SGM is very rare esophageal condition with an incidence around 0.00465% and an occurrence rate of 0.41 per year. There were 57.1% of senior endoscopists identified 8 episodes of SGM. In contrast, 7.7% of junior endoscopists identified SGM in only 2 episodes. Moreover, we investigated the difference in endoscopic biopsy attempt rate between the senior and junior endoscopist (P = 0.0001). The senior endoscopists had more motivation to look for SGM than did junior endoscopists (P = 0.01). We concluded that SGM of the esophagus is rare condition that is easily and not recognized in endoscopy studies omitting pathological review.
PMCID: PMC4097163  PMID: 25032211
Esophagus; Sebaceous gland; Metaplasia; Endoscopy; Endoscopist
3.  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
4.  Interventional radiology in living donor liver transplant 
The shortage of deceased donor liver grafts led to the use of living donor liver transplant (LDLT). Patients who undergo LDLT have a higher risk of complications than those who undergo deceased donor liver transplantation (LT). Interventional radiology has acquired a key role in every LT program by treating the majority of vascular and non-vascular post-transplant complications, improving graft and patient survival and avoiding, in the majority of cases, surgical revision and/or re-transplant. The aim of this paper is to review indications, diagnostic modalities, technical considerations, achievements and potential complications of interventional radiology procedures after LDLT.
PMCID: PMC4033459  PMID: 24876742
Portal vein; Hepatic artery; Hepatic vein; Bile duct; Living donor liver transplantation; Liver transplant
5.  Homogeneous phenomenon of the graft when using different genotype characteristic of recipients/donors in living donor liver transplantation 
World Journal of Hepatology  2013;5(11):642-648.
AIM: To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18 of the liver graft after living donor liver transplantation (LDLT).
METHODS: We identified the proportional change of the CYP3A5*3, MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119 liver graft biopsy samples used with the pyrosequencing technique after LDLT. Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms (SNPs). All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3, MDR1-3435 or CYP3A4*18 were excluded.
RESULTS: The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3, MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient. The proportional changes of G to A alleles of the 119 samples of CYP3A5*3 (included A > A/G, A/G > A, A/G > G, G > A, G > A/G and A > G), C to T alleles of the 108 samples of MDR1-3435 (included C > C/T, C/T > C, C/T > T, T > C/T and T > C), and T to C alleles of 15 samples of CYP3A4*18 (included T/C > T and T > C/T) were significant different between the recipients and the liver graft biopsy samples (P < 0.0001) and less difference when compared with the donors in the pyrosequencing analysis after LDLT.
CONCLUSION: The CYP3A5*3, MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.
PMCID: PMC3847948  PMID: 24303093
Pyrosequencing; CYP3A5*3; MDR1-3435; CYP3A4*18; Liver biopsy; Living donor liver transplantation
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.  Delayed presentation of intrathoracic esophageal perforation after pneumatic dilation for achalasia 
Pneumatic dilation (PD) is considered to be a safe and effective first line therapy for achalasia. The major adverse event caused by PD is esophageal perforation but an immediate gastrografin test may not always detect a perforation. It has been reported that delayed management of perforation for more than 24 h is associated with high mortality. Surgery is the treatment of choice within 24 h, but the management of delayed perforation remains controversial. Hereby, we report a delayed presentation of intrathoracic esophageal perforation following PD in a 48-year-old woman who suffered from achalasia. She completely recovered after intensive medical care. A review of the literature is also discussed.
PMCID: PMC2747072  PMID: 19764103
Intrathoracic esophageal perforation; Delayed presentation; Pneumatic dilation; Esophageal achalasia
9.  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
10.  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
11.  Dextrose in the banked blood products does not seem to affect the blood glucose levels in patients undergoing liver transplantation 
AIM: Hyperglycemia commonly seen in liver transplantation (LT) has often been attributed to the dextrose in the storage solution of blood transfusion products. The purpose of the study is to compare the changes of the blood glucose levels in transfused and non-transfused patients during LT.
METHODS: A retrospective study on 60 biliary pediatric patients and 16 adult patients undergoing LT was carried out. Transfused pediatric patients were included in Group I (GI), those not transfused in Group II (GII). Twelve adult patients were not given transfusion and assigned to Group III (GIII); whereas, four adult patients who received massive transfusion were assigned to Group IV (GIV). The blood glucose levels, volume of blood transfused, and the volume of crystalloid infused were recorded, compared and analyzed.
RESULTS: Results showed that the changes in blood glucose levels during LT for both non-transfused and minimally transfused pediatric groups and non-transfused and massively-transfused adult groups were almost the same.
CONCLUSION: We conclude that blood transfusion does not cause significant changes in the blood glucose levels in this study.
PMCID: PMC4305918  PMID: 15884124
Organ; Liver surgery; Transplantation; Anesthesia; General monitoring; Blood glucose transfusion; Bank blood component; Infusion; 5% dextrose in 1/4 saline.
12.  Impact of pre-operative transarterial embolization on the treatment of hepatocellular carcinoma with liver transplantation 
AIM: To determine the effectiveness of pre-liver transplant (LT) transarterial embolization (TAE) in treating hepatocellular carcinoma (HCC) and the patient categories, which are likely to have a good outcome after LT.
METHODS: Twenty-nine patients with hepatitis-related cirrhosis and unresectable HCC after LT were studied over a 7-year period. The patients were divided into two groups: group A patients (19/29) received pre-LT TAE, whereas group B (10/29) underwent LT without prior TAE. According to Milan criteria, group A patients were further subdivided into: group A1 (12/19) who met the criteria, and group A2 (7/19) who did not. Patient survivals were compared.
RESULTS: In the explanted liver, CT images correlated well with pathological specimens showing that TAE induced massive tumor necrosis (>85%) in 63.1% of patients in group A and all 7 patients in group A2 exhibited tumor downgrading that met Milan criteria. The overall 5-year actuarial survival rate was 80.6%. The TAE group had a better survival (84% at 5 years) than the non-TAE (75% at 4 years). The 3-year survival of group A2 (83%) was also higher than that of group A1 (79%). Tumor necrosis >85% was associated with excellent survival of 100% at 3 years, which was significantly better than the others who showed <85% tumor necrosis (57.1% at 3 years) or who did not have TAE (75% at 3 years).
CONCLUSION: TAE is an effective treatment for HCC before LT. Excellent long-term survival was achieved in patients that did not fit Milan criteria. Our results broadened and redefined the selection policy for LT among patients with HCC. Meticulous pre-LT TAE helps in further reducing the rate of dropout from waiting lists and should be considered for patients with advanced HCC.
PMCID: PMC4305683  PMID: 15770717
Hepatocellular carcinoma; Liver transplantation; Transarterial embolization
13.  Induction of Antinuclear Antibodies by De Novo Autoimmune Hepatitis Regulates Alloimmune Responses in Rat Liver Transplantation 
Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.
PMCID: PMC3886613  PMID: 24454474
14.  Endoscopic Biopsy as Quality Assurance for Endoscopic Services 
PLoS ONE  2013;8(11):e78557.
Gastroendoscopy (GS) procedures are not only performed by gastroenterologists (GE) but also by hepatologists (HT) in many countries. Endoscopic biopsy (EBx) remains the gold standard for the investigation and documentation of esophago-gastro-duodenal pathology. EBx is subjectively performed by an endoscopist, and the level of skill and experience of the endoscopist may affect the quality of the endoscopic service. Reasons for this discrepancy included lack of experience practitioners to order EBx when required of GS issues between in GE and HT limit access. Ideally, services should be safe and of high quality. This study assessed the EBx/GS ratio as the endoscopic quality assurance as an index of GS services. This was a cohort study of endoscopists at Kaohsiung Chang Gung Memorial Hospital, a teaching hospital in southern Taiwan. There were 34,570 episodes of EBx in 199,877 GS procedures. The 25 endoscopists were divided into GE (n = 13) and HT (n = 12) groups, and correlation coefficients were calculated over a 14.5-year duration of intervention. The Trimmean of EBx/GS was 19.29% in 14.5 years (34570/199877 with Trimmean 0.2 percentile ratio correlations), and the Pearson correlation coefficient was 0.90229. There were significantly more EBx procedures in the GE group than in the HT group at 1 and 5 years (21.5% vs. 15.1% and 20.9% vs. 17.3%, respectively, P<0.00001). Junior GE attempted significantly more EBx than both the senior GE (24.06% vs. 20.41%, P<0.0001), and junior HT (24.06% vs. 13.2%, P<0.0001). In conclusion, quality assurance for gastrointestinal endoscopy involves numerous aspects of unit management and patient safety. Quality measures used with the EBx/GS ratio may be one of the best ways to ensure the quality of endoscopic procedures in a teaching hospital.
PMCID: PMC3827051  PMID: 24265698
15.  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
16.  Pyrosequencing to Identify Homogeneous Phenomenon When Using Recipients/Donors with Different CYP3A5*3 Genotypes in Living Donor Liver Transplantation 
PLoS ONE  2013;8(8):e71314.
This study used pyrosequencing to determine the proportional distribution of CYP3A5*3 genotypes to further confirm the homogeneous phenomenon that is observed when recipients and donors in living donor liver transplantation (LDLT) have a different single nucleotide polymorphism (SNP) genotype. We enrolled 42 recipient/living donor pairs and the SNPs of CYP3A5*3 were identified by polymerase chain reaction-restriction fragment length polymorphism. We performed 120 liver graft biopsies as part of clinical investigations after LDLT. Pyrosequencing of the CYP3A5*3 SNPs revealed that among the 16 recipients with the G/G genotype, 94.68% had the G and 5.32% the A allele. Among the 14 recipients with the A/G genotype, 78.08% had the G and 21.92% the A allele, and among the 12 recipients with the A/A genotype, 18.45% had the G and 81.55% the A allele. Among the 12 donors with the G/G genotype, 93.85% had the G and 6.14% the A allele. Among the 26 donors with the A/G genotype, 75.73% had the G and 24.27% the A allele, and among the 4 donors with the A/A genotype, 11.09% had the G and 88.91% the A allele. There were a total of 120 liver graft biopsy samples; among the 37 recipients with the G/G genotype, 89.74% had the G and 10.26% the A allele, among the 70 recipients with the A/G genotype, 71.57% had the G and 28.43% the A allele, and among the 13 recipients with the A/A genotype, 48.25% had the G and 51.75% the A allele. The proportional distribution of G and A alleles of the CYP3A5*3 SNP between recipients/donors and liver grafts after LDLT was significantly different (p<0.001). Pyrosequencing was useful in identifying detailed proportional changes of the CYP3A5*3 SNP allele distribution, and to confirm the homogeneous phenomenon when recipients and donors in LDLT have a different genotype.
PMCID: PMC3738598  PMID: 23951129
17.  Telbivudine and adefovir combination therapy for patients with chronic lamivudine-resistant hepatitis B virus infections 
Archives of Virology  2013;159(1):29-37.
We evaluated second-line salvage therapy with adefovir + telbivudine (group 1), adefovir followed by adefovir + telbivudine (group 2), or lamivudine + adefovir followed by adefovir + telbivudine (group 3) in hepatitis B patients with an inadequate virologic response to lamivudine treatment. Simple linear regression analysis showed that for each additional month of treatment, the most significant reduction in viral load occurred in group 1 (HBV DNA [Log10 IU/mL]: group 1, −0.149; group 2, -0.081; group 3, −0.123). Generalized estimating equation analysis revealed that compared to group 1, hepatitis B virus (HBV) DNA levels were 1.203 and 0.443 Log10 IU/mL higher in groups 2 and 3, respectively. Overall, a significant reduction in viral load (−0.060 Log10 IU/mL) was observed for each additional month of treatment. Adefovir + telbivudine treatment resulted in a significant reduction in HBV DNA levels. Moreover, telbivudine treatment resulted in a significant reduction in viral load (−0.050 Log10 IU/mL) compared to lamivudine treatment after the emergence of lamivudine resistance.
Electronic supplementary material
The online version of this article (doi:10.1007/s00705-013-1786-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3888503  PMID: 23857507
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.  Biological interactions of CYP2C19 genotypes with CYP3A4*18, CYP3A5*3, and MDR1-3435 in living donor liver transplantation recipients 
Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. The CYP3A4*18, CYP3A5*3, and MDR1-3435 variant alleles are very important, particularly in tacrolimus metabolism in organ transplant rejection.
The aim of this study is o explore possible interactions among different CYP2C19 genotypes, namely, between homozygous extensive metabolizers (HomEM), heterozygous extensive metabolizers (HetEM), and poor metabolizers (PM), and the CYP3A4*18, CYP3A5*3, and MDR1-3435 variants in living donors and patients who received a living donor liver transplant (LDLT).
This prospective study enrolled 133 living donors and 133 corresponding recipients. On the basis of the HomEM, HetEM, and PM CYP2C19 genotypes, the distributions of CYP3A4*18 (exon 10; T878C), CYP3A5*3 (intron 3; A6986G), and MDR1-3435 (exon 26; C3435T) genotypes were analyzed for single nucleotide polymorphisms among donors and recipients.
Among 102 HomEM genotypes, including 56 donors and 46 recipients, 91.2% of individuals harbored the T/T genotype of CYP3A4*18; 53.9% possessed G/G, and 34.3% had A/G genotypes of CYP3A5*3; and 38.2% had C/C and 50.0% had C/T genotypes at MDR1-3435. Among 130 HetEM genotypes, including 58 donors and 72 recipients, 97.7% of individuals possessed T/T genotype at CYP3A4*18; 50.0% harbored G/G and 41.5% had A/G genotypes at CYP3A5*3; and 40.0% had C/C and 49.2% had C/T genotypes at MDR1-3435. In 34 PMs, including 19 donors and 15 recipients, 88.2% had T/T genotypes at CYP3A4*18; 41.2% had G/G and 58.8% had A/G genotypes at CYP3A5*3; and 47.1% possessed C/C and 47.1% had C/T genotypes at MDR1-3435. On the basis of the CYP2C19 genotypes, no statistically significant distribution of genotypes were observed between donors and recipients for all genotypes of CYP3A4*18, CYP3A5*3, and MDR1-3435 (P >0.05).
In conclusion, the CYP2C19 genotypes do not affect the expression of CYP3A4*18, CYP3A5*3, or MDR1-3435 variants, which are independently distributed among donors and recipients during LDLT.
PMCID: PMC3643843  PMID: 23617933
Living donor liver transplantation; Cytochrome P450; CYP3A4*18; CYP3A5*3; MDR1-3435; CYP2C19 genotypes
20.  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
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.  Immunological and Regenerative Aspects of Hepatic Mast Cells in Liver Allograft Rejection and Tolerance 
PLoS ONE  2012;7(5):e37202.
The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow−derived mast cells (BMMCs) co-cultured with naïve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.
PMCID: PMC3352886  PMID: 22615941
23.  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
24.  Adaptor protein Shc acts as an immune-regulator for the LPS-stimulated maturation of bone marrow-derived dendritic cells 
BMC Immunology  2011;12:32.
The Shc isoforms is known to mediate immune responses and has been indicated as a negative regulator of autoimmunity and lymphocyte activation. We aimed to evaluate the immune-regulatory role of Shc in rat bone marrow-derived DCs in the maturation process triggered by LPS.
We found that, in response to LPS, expression of Shc proteins was induced and that neutralization of Shc inhibited the LPS-induced transient phosphorylation of p52Shc on pTyr239/240 in DCs of Lewis (LEW; RT1l) rats. Moreover, the significantly enhanced expression of IL-10 and the surface level of costimulatory molecule CD80, as well as suppressed expression of IL-6 and IL-12 in the Shc-silenced DCs were also observed. Similar IκB phosphorylation occurred in Shc-silenced DCs primed by LPS, indicating Shc is not associated with NF-κB pathway. We further demonstrate that Shc blockade on LPS-treated DCs results in significant increase of the overall STAT3 phosphorylation and the relative levels of phospho-STAT3 in the nuclear fraction. STAT3 activation by LPS with or without Shc blockade was totally abolished by SU6656, a selective Src family kinases inhibitor, underscoring the critical role of Src-mediated activation.
We conclude that Shc blockade in LPS-primed DC leads to the development of tolerogenic DC via Src-dependent STAT3 activation and that adaptor protein Shc might play a pivotal role in mediating immunogenic and tolerogenic properties of DCs.
PMCID: PMC3123310  PMID: 21612602

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