Publications by authors named "Deng-Chyang Wu"

298 Publications

The impact of urine microbiota in patients with lower urinary tract symptoms.

Ann Clin Microbiol Antimicrob 2021 Apr 15;20(1):23. Epub 2021 Apr 15.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Introduction: Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS).

Materials And Methods: We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at - 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson's correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples.

Results: We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman's correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P < 0.05).

Conclusion: Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.
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http://dx.doi.org/10.1186/s12941-021-00428-9DOI Listing
April 2021

Dimethyl sulfoxide stimulates the AhR-Jdp2 axis to control ROS accumulation in mouse embryonic fibroblasts.

Cell Biol Toxicol 2021 Mar 15. Epub 2021 Mar 15.

Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

The aryl hydrocarbon receptor (AhR) is a ligand-binding protein that responds to environmental aromatic hydrocarbons and stimulates the transcription of downstream phase I enzyme-related genes by binding the cis element of dioxin-responsive elements (DREs)/xenobiotic-responsive elements. Dimethyl sulfoxide (DMSO) is a well-known organic solvent that is often used to dissolve phase I reagents in toxicology and oxidative stress research experiments. In the current study, we discovered that 0.1% DMSO significantly induced the activation of the AhR promoter via DREs and produced reactive oxygen species, which induced apoptosis in mouse embryonic fibroblasts (MEFs). Moreover, Jun dimerization protein 2 (Jdp2) was found to be required for activation of the AhR promoter in response to DMSO. Coimmunoprecipitation and chromatin immunoprecipitation studies demonstrated that the phase I-dependent transcription factors, AhR and the AhR nuclear translocator, and phase II-dependent transcription factors such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) integrated into DRE sites together with Jdp2 to form an activation complex to increase AhR promoter activity in response to DMSO in MEFs. Our findings provide evidence for the functional role of Jdp2 in controlling the AhR gene via Nrf2 and provide insights into how Jdp2 contributes to the regulation of ROS production and the cell spreading and apoptosis produced by the ligand DMSO in MEFs.
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http://dx.doi.org/10.1007/s10565-021-09592-2DOI Listing
March 2021

Gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor: A case report and review of the literature.

World J Clin Cases 2021 Feb;9(4):838-846

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

Background: Gastric gastrointestinal stromal tumor (GIST) is the most common etiology of gastroduodenal intussusception. Although gastroduodenal intussusception caused by gastric GIST is mostly treated by surgical resection, the first case of gastroduodenal intussusception caused by gastric GIST was treated by endoscopic submucosal dissection (ESD) in Japan in 2017.

Case Summary: An 84-year-old woman presented with symptoms of postprandial fullness with nausea and occasional vomiting for a month. Initially, she visited a local clinic for help, where abdominal sonography revealed a space-occupying lesion around the liver, so she was referred to our hospital for further confirmation. Abdominal sonography was repeated, which revealed a mass with an alternating concentric echogenic lesion. Esophagogastroduodenoscopy (EGD) was performed under the initial impression of gastric cancer with central necrosis and showed a tortuous distortion of gastric folds down from the lesser curvature side to the duodenal bulb with stenosis of the gastric outlet. EGD was barely passed through to the 2nd portion of the duodenum and a friable ulcerated mass was found. Several differential diagnoses were suspected, including gastroduodenal intussusception, gastric cancer invasion to the duodenum, or pancreatic cancer with adherence to the gastric antrum and duodenum. Abdominal computed tomography for further evaluation was arranged and showed gastroduodenal intussusception with a long stalk polypoid mass 5.9 cm in the duodenal bulb. Under the impression of gastroduodenal intussusception, ESD was performed at the base of the gastroduodenal intussusception; unfortunately, a gastric perforation was found after complete resection was accomplished, so gastrorrhaphy was performed for the perforation and retrieval of the huge polypoid lesion. The gastric tumor was pathologically proved to be a GIST. After the operation, there was no digestive disturbance and the patient was discharged uneventfully on the 10th day following the operation.

Conclusion: We present the second case of gastroduodenal intussusception caused by GIST treated by ESD. It is also the first case report of gastroduodenal intussusception by GIST in Taiwan, and endoscopic reduction or resection is an alternative treatment for elderly patients who are not candidates for surgery.
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http://dx.doi.org/10.12998/wjcc.v9.i4.838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852652PMC
February 2021

Comparison of Endoscopic Submucosal Dissection Application on Mucosal Tumor and Subepithelial Tumor in stomach.

J Cancer 2021 1;12(3):765-770. Epub 2021 Jan 1.

Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Endoscopic submucosal dissection is minimal invasive endoscopic procedure to deal with gastric tumor. Initially, it was developed to resect mucosal neoplasm since 2000 and extended its application to submucosal tumor in the following years. Although the basic ESD skills are similar in gastric mucosal tumor and subepithelial tumor, the success rate, complication may be different between the two types of gastric tumor resection. This retrospective study is conducted to analyze the ESD procedure in gastric mucosal tumor and subepithelial tumor. From 2007 to 2016, we reviewed all patients who underwent endoscopic submucosal dissection for gastric mucosal tumor and subepithelial tumor in Kaohsiung Medical University Hospital. Totally, 35 patients with gastric subepithelial tumor and 41 patients with gastric mucosal tumor received endoscopic submucosal dissection are enrolled. Among 35 patients with subepithelial tumor, 32 (91.4%) patients achieved curative treatment. 1 patient received emergent operation and 2 patients received salvage operation to complete tumor resection. 8 patients (22.9%) occurred perforation and no delay bleeding was found. Among 41 patients with mucosal neoplasm, 30 (71.4%) patients achieved curative treatment. 2 patients received emergent operation and 9 patients received salvage operation to complete tumor resection. 9 patients (21.9%) occurred complication, 6 patients occurred delay bleeding and 3 patients had perforation. Comparing ESD between gastric mucosal tumor and subepithelial tumor, ESD had similar efficiency in curative treatment. However, ESD in subepethelial tumor encountered higher perforation and lesser delay bleeding.
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http://dx.doi.org/10.7150/jca.47653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778549PMC
January 2021

Efficacy and safety of vedolizumab in Crohn's disease in patients from Asian countries in the GEMINI 2 study.

Intest Res 2021 Jan 31;19(1):83-94. Epub 2020 Dec 31.

Takeda Pharmaceutical International AG, Zurich, Switzerland.

Background/aims: The efficacy and safety of vedolizumab in moderate-to-severely active Crohn's disease (CD) were demonstrated in the GEMINI 2 study (NCT00783692). This post-hoc exploratory analysis aimed to assess the efficacy and safety of vedolizumab in the subgroup of patients from Asian countries.

Methods: During the induction phase (doses at day 1, 15), clinical remission, enhanced clinical response, and change in C-reactive protein at 6 weeks; during the maintenance phase, clinical remission, enhanced clinical response, glucocorticoid-free remission and durable clinical remission at 52 weeks, were the efficacy outcomes of interest. Efficacy and safety of vedolizumab compared to placebo were assessed in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) using descriptive analyses.

Results: During the induction phase, in Asian countries (n = 51), 14.7% of the vedolizumab-treated patients achieved clinical remission at week 6 compared to none with placebo (difference, 14.7%; 95% confidence interval, 15.8%-43.5%). In non-Asian countries (n = 317), the remission rate at week 6 with vedolizumab was 14.5%. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks and placebo were 41.7%, 36.4%, and 0%, respectively; while enhanced clinical response rates were 41.7%, 63.6%, and 42.9%, respectively. During induction, 39.7% of patients with vedolizumab experienced an adverse event compared to 58.8% of patients with placebo, and vedolizumab was generally well-tolerated.

Conclusions: This post-hoc analysis demonstrates the treatment effect and safety of vedolizumab in moderateto-severely active CD in patients from Asian countries.
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http://dx.doi.org/10.5217/ir.2019.09160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873405PMC
January 2021

Trend of changes in antibiotic resistance in from 2013 to 2019: a multicentre report from Taiwan.

Therap Adv Gastroenterol 2020 10;13:1756284820976990. Epub 2020 Dec 10.

Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833 Chang Gung University College of Medicine, Taoyuan City.

Background: Antibiotic resistance plays a crucial role in the treatment failure of infection. This study aimed to determine the trend of changes in the primary, secondary and tertiary antibiotic resistance of in Taiwan over the last 7 years.

Methods: We retrospectively analysed -infected isolates from patients with primary resistance ( = 1369), secondary resistance ( = 196) and tertiary resistance ( = 184) from January 2013 to December 2019. The strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the Epsilometer test method.

Results: A progressively higher primary resistance rate was observed for clarithromycin (11.8-20.4%,  = 0.039 in χ test for linear trend), levofloxacin (17.3-38.8%,  < 0.001) and metronidazole (25.6-42.3%,  < 0.001) among naïve patients who received first-line eradication therapy. The dual primary resistance to clarithromycin and metronidazole also progressively increased in a linear trend (2.4-10.4%,  = 0.009). For secondary resistance, an increase was observed for levofloxacin (30.5-64.7%,  = 0.006) and metronidazole (40.5-77.4%,  < 0.001). For tertiary resistance, the observed increase was even more significant for levofloxacin (65.9-100.0%,  = 0.106) and metronidazole (44.4-88.2%, < 0.001). The resistance to amoxicillin and tetracycline remained very low in Taiwan regardless of primary, secondary and tertiary resistance.

Conclusion: Primary, secondary and tertiary antibiotic resistance to clarithromycin, levofloxacin and metronidazole for has been increasing in Taiwan since 2013. Treatment should be targeted for eradication success rates of more than 90%. Third-line treatment should be based on antibiotic susceptibility.
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http://dx.doi.org/10.1177/1756284820976990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734532PMC
December 2020

Herbal medicines in functional dyspepsia-Untapped opportunities not without risks.

Neurogastroenterol Motil 2021 02 30;33(2):e14044. Epub 2020 Nov 30.

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in-depth review of this is timely.

Aims/purpose: To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia.

Methods: We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated.

Results: We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well-defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation.

Conclusions: We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.
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http://dx.doi.org/10.1111/nmo.14044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900952PMC
February 2021

Gut Fecal Microbiota Transplant in a Mouse Model of Orthotopic Rectal Cancer.

Front Oncol 2020 28;10:568012. Epub 2020 Oct 28.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

The gut microbiota is reported to play an important role in carcinogenesis and the treatment of CRC. SW480 and SW620 colon cancer cells integrated with infrared fluorescent proteins were injected into the rectal submucosa of nude mice. In the subsequent 30 days, we observed tumor growth weekly using an imaging system. The bacterial solution was infused anally into the mice to perform bacterial transplant. Phosphate-buffered saline, , and solutions were infused individually. The 16S ribosomal DNA (rDNA) and polymerase chain reaction of murine feces were investigated to confirm the colonization of target bacteria. In the SW620 orthotopic xenograft rectal cancer model, 4 of 5 mice developed rectal cancer by 30 days after submucosal injection. In the SW480 orthotopic xenograft rectal cancer model, 2 of 6 mice developed rectal cancer by 30 days after submucosal injection. For the 16S rDNA analysis, the mice receiving the bacterial solution infusion demonstrated positive findings for and . With the successful establishment of a mouse model of orthotopic rectal cancer and transplant of target bacteria, we can further explore the relationship between gut microbiota and CRC. The role of fecal microbiota transplant in the treatment and alleviation of adverse events of chemotherapy in CRC could be clarified in subsequent studies.
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http://dx.doi.org/10.3389/fonc.2020.568012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658813PMC
October 2020

Impact of cap-assisted colonoscopy during transendoscopic enteral tubing: A randomized controlled trial.

World J Gastroenterol 2020 Oct;26(39):6098-6110

Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China.

Background: Colonic transendoscopic enteral tubing (TET) requires double cecal intubation, raising a common concern of how to save cecal intubation time and make the tube stable. We hypothesized that cap-assisted colonoscopy (CC) might reduce the second cecal intubation time and bring potential benefits during the TET procedure.

Aim: To investigate if CC can decrease the second cecal intubation time compared with regular colonoscopy (RC).

Methods: This prospective multicenter, randomized controlled trial was performed at four centers. Subjects ≥ 7 years needing colonic TET were recruited from August 2018 to January 2020. All subjects were randomly assigned to two groups. The primary outcome was the second cecal intubation time. Secondary outcomes included success rate, insertion pain score, single clip fixation time, purpose and retention time of TET tube, length of TET tube inserted into the colon, and all procedure-related (serious) adverse events.

Results: A total of 331 subjects were randomized to the RC ( = 165) or CC ( = 166) group. The median time of the second cecal intubation was significantly shorter for CC than RC (2.2 min 2.8 min, < 0.001). In patients with constipation, the median time of second cecal intubation in the CC group ( = 50) was shorter than that in the RC group ( = 43) (2.6 min 3.8 min, = 0.004). However, no difference was observed in the CC ( = 42) and RC ( = 46) groups of ulcerative colitis patients (2.0 min 2.5 min, = 0.152). The insertion pain score during the procedure in CC ( = 14) was lower than that in RC ( = 19) in unsedated colonoscopy (3.8 ± 1.7 5.4 ± 1.9; = 0.015). Multivariate analysis revealed that only CC (odds ratio [OR]: 2.250, 95% confidence interval [CI]: 1.161-4.360; = 0.016) was an independent factor affecting the second cecal intubation time in difficult colonoscopy. CC did not affect the colonic TET tube's retention time and length of the tube inserted into the colon. Moreover, multivariate analysis found that only endoscopic clip number (OR: 2.201, 95%CI: 1.541-3.143; < 0.001) was an independent factor affecting the retention time. Multiple regression analysis showed that height (OR: 1.144, 95%CI: 1.027-1.275; = 0.014) was the only independent factor influencing the length of TET tube inserted into the colon in adults.

Conclusion: CC for colonic TET procedure is a safe and less painful technique, which can reduce cecal intubation time.
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http://dx.doi.org/10.3748/wjg.v26.i39.6098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584059PMC
October 2020

Plastic wrap combined with alcohol wiping is an effective method of preventing bacterial colonization on mobile phones.

Medicine (Baltimore) 2020 Oct;99(44):e22910

Department of Superintendent office, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Introduction: Using mobile phones for communication in emergency departments is a common practice; however, several studies have demonstrated that they may act as vectors for bacteria and viruses. This study evaluated the effectiveness of plastic wrapping in decreasing bacterial contamination on mobile phone surfaces.

Method: We used culture dishes and a luminometer to detect bacterial colonies and contamination on the phone surfaces.

Result: Our experiment showed that bacterial colonies exist on mobile phones before and after work. We found that wiping with 75% alcohol sanitizers effectively reduces the number of colonies on either a mobile phone or a temporary plastic covering. In addition, we found that bacterial colonies do not contaminate or adhere to plastic wrap any easier than to mobile phones.

Conclusion: These results demonstrated the effectiveness of plastic wrap for protecting mobile phone surfaces against bacterial colonization. In addition, applying a layer of plastic wrap protects the phone from potential damage due to the alcohol.
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http://dx.doi.org/10.1097/MD.0000000000022910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598847PMC
October 2020

NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-Associated gastric cancer.

Biomed Pharmacother 2020 Dec 28;132:110869. Epub 2020 Oct 28.

Department of Medical Research, E-Da Hospital/E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan. Electronic address:

Helicobacter pylori infection is an important pathogenic risk factor for gastric cancer, but it is still unclear what tumor markers for gastric cancer induced by H. pylori can be consistently detected. Using an miRNA microarray, we found that miR-18a-3p (6.02-fold) and miR-4286 (5.73-fold) were significantly increased in H. pylori- associated gastric cancer. In a cohort of gastric cancer patients (N = 104), serum expression of miR-18a-3p and miR-4286 was positively and significantly correlated with H. pylori; furthermore, miR-18a-3p was positively correlated with invasion (P = 0.029), and miR-4286 was positively correlated with tumor stage (P = 0.033), tumor size (P = 0.041), and lymph node metastasis (P = 0.009). Overexpression of miR-18a-3p and miR-4286 also increased cancer cell proliferation and motility and both inhibited expression of BZRAP1, resulting in tumor progression in vitro. In addition, lipopolysaccharide co-mediated the expression of miR-18a-3p and miR-4286 by activating the NF-κB transcription factor, but TAK-242 (TLR4 inhibitor) blocked this effect. These results demonstrate that serum miR-18a-3p and miR-4286 levels in H. pylori-associated gastric cancer may be useful prognostic biomarkers and suggest a novel signaling pathway of targeting BZRAP1 in gastric cancer.
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http://dx.doi.org/10.1016/j.biopha.2020.110869DOI Listing
December 2020

Screening and eradication of for gastric cancer prevention: the Taipei global consensus.

Gut 2020 12 1;69(12):2093-2112. Epub 2020 Oct 1.

Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

Objective: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of for prevention of gastric cancer (GC).

Methods: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed.

Results: Consensus was reached in 26 statements. At an individual level, eradication of reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of .

Conclusion: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with . Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of should be considered in populations at higher risk of GC.
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http://dx.doi.org/10.1136/gutjnl-2020-322368DOI Listing
December 2020

Efficacy and safety of vedolizumab in ulcerative colitis in patients from Asian countries in the GEMINI 1 study.

Intest Res 2021 Jan 4;19(1):71-82. Epub 2020 Sep 4.

Takeda Pharmaceutical International AG, Zurich, Switzerland.

Background/aims: The efficacy and safety of vedolizumab in moderate to severely active ulcerative colitis (UC) have been demonstrated in the GEMINI 1 study (NCT00783718). This post-hoc exploratory analysis sought to establish the efficacy and safety of vedolizumab in a subgroup of patients from Asian countries with UC from GEMINI 1.

Methods: Efficacy outcomes of interest were clinical response, clinical remission and mucosal healing at week 6 (induction phase); and clinical remission, durable clinical response, durable clinical remission, mucosal healing and glucocorticoid-free remission at week 52 (maintenance phase). Differences in outcome rates between vedolizumab and placebo in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) were assessed using descriptive analyses, and efficacy and safety compared between Asian and non-Asian countries.

Results: During induction, in Asian countries (n = 58), clinical response rates at week 6 with vedolizumab and placebo were 55.2% and 24.1%, respectively (difference 31.0%; 95% confidence interval: 7.2%-54.9%). In non-Asian countries (n = 316), response rates at week 6 with vedolizumab and placebo were 45.9% and 25.8%, respectively. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 8 weeks, vedolizumab administered every 4 weeks and placebo were 9.1%, 36.8%, and 31.6%, respectively; corresponding rates for mucosal healing were 45.5%, 47.4%, and 47.4%, respectively. Vedolizumab was well-tolerated; adverse event frequency was comparable in Asian and non-Asian countries.

Conclusions: In patients from Asian countries, the efficacy and safety of vedolizumab in treatment of UC were broadly consistent with that in the overall study population.
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http://dx.doi.org/10.5217/ir.2019.09159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873399PMC
January 2021

Supplemental home parenteral nutrition improved nutrition status with comparable quality of life in malnourished unresectable/metastatic gastric cancer receiving salvage chemotherapy.

Support Care Cancer 2021 Apr 22;29(4):1977-1988. Epub 2020 Aug 22.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.

Background: Even with significant advances in surgical techniques and treatment, salvage chemotherapy remains the major treatment strategy for patients with unresectable or metastatic gastric cancer (GC). Practical and technical advances have simplified safe and convenient use of supplemental home parenteral nutrition (HPN). We aimed to clarify the role of HPN in patients with incurable GC undergoing salvage chemotherapy.

Methods: We enrolled 25 patients with GC with a nutritional risk index (NRI) of ≦ 97.5 undergoing HPN. Their nutritional status, laboratory data, and quality of life (QoL) were analyzed using the Research and Treatment of Cancer quality of life questionnaire-C30 before and after HPN administration at 0.5, 1, 2, and 3 months. We enrolled 25 patients with an NRI of > 97.5 not undergoing HPN as the control group.

Results: Total protein (P = 0.008), prealbumin (P < 0.001), and total cholesterol (P = 0.023) levels improved significantly after 0.5 months of HPN administration. The study group also demonstrated a marked improvement in nitrogen balance (P = 0.004) and prealbumin levels (P < 0.012) after 1 month. Gains in body weight after 1 month and body mass index after 2 months of HPN administration remained comparable with those of the control group. Global QoL scores were maintained and comparable with those of the control group.

Conclusions: Supplemental HPN therapy for malnourished patients with unresectable or metastatic GC undergoing salvage chemotherapy is feasible and revealed marked improvement in nutritional status. Early HPN intervention should be considered an important part of palliative treatment for advanced GC.
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http://dx.doi.org/10.1007/s00520-020-05687-4DOI Listing
April 2021

Asian Pacific Association of Gastroenterology (APAGE) Inflammatory Bowel Disease (IBD) Working Party guidelines on IBD management during the COVID-19 pandemic.

JGH Open 2020 Jun 5;4(3):320-323. Epub 2020 Jun 5.

Duke-NUS Medical School Singapore.

The COVID-19 pandemic, secondary to SARS-CoV-2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long-term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face-to-face clinic follow ups and non-urgent procedures should be kept to a minimum.
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http://dx.doi.org/10.1002/jgh3.12362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273734PMC
June 2020

Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells.

J Exp Clin Cancer Res 2020 Jun 3;39(1):100. Epub 2020 Jun 3.

Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung, 807, Taiwan.

Human pluripotent embryonic stem cells have two special features: self-renewal and pluripotency. It is important to understand the properties of pluripotent stem cells and reprogrammed stem cells. One of the major problems is the risk of reprogrammed stem cells developing into tumors. To understand the process of differentiation through which stem cells develop into cancer cells, investigators have attempted to identify the key factors that generate tumors in humans. The most effective method for the prevention of tumorigenesis is the exclusion of cancer cells during cell reprogramming. The risk of cancer formation is dependent on mutations of oncogenes and tumor suppressor genes during the conversion of stem cells to cancer cells and on the environmental effects of pluripotent stem cells. Dissecting the processes of epigenetic regulation and chromatin regulation may be helpful for achieving correct cell reprogramming without inducing tumor formation and for developing new drugs for cancer treatment. This review focuses on the risk of tumor formation by human pluripotent stem cells, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and clinical applications of regenerative medicine.
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http://dx.doi.org/10.1186/s13046-020-01584-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268627PMC
June 2020

Hemodialysis Increases the Risk of Lower Gastrointestinal Bleeding and Angiodysplasia Bleeding: A Nationwide Population Study.

Gastroenterol Res Pract 2020 3;2020:7206171. Epub 2020 Mar 3.

Department of Medicine, An Nan Hospital, China Medical University, Taiwan.

Background: Patients with chronic kidney disease (CKD) with or without hemodialysis were considered to have bleeding tendency and higher risk for gastrointestinal (GI) bleeding. Previous studies had documented that hemodialysis may increase the gastroduodenal ulcer bleeding. Few studies evaluated the relationship between CKD and lower GI bleeding. . An observational cohort study design was conducted. The end-stage renal disease (ESRD) patients receiving regular hemodialysis (dialysis CKD), CKD patients without dialysis (dialysis-free CKD), and controls were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. These three group subjects were matched by age, sex, comorbidity, and enrollment time in a 1 : 2 : 2 ratio. The Cox proportional hazard regression models were used to identify the potential risk factors for lower gastrointestinal bleeding.

Results: Dialysis CKD patients ( = 574) had a higher incidence of lower GI bleeding than dialysis-free CKD patients ( = 574) had a higher incidence of lower GI bleeding than dialysis-free CKD patients ( = 574) had a higher incidence of lower GI bleeding than dialysis-free CKD patients ( < 0.001). Multivariate analysis showed that extreme old age (age ≥ 85), male gender, dialysis-free CKD, and dialysis CKD were independent factors of lower GI bleeding. Additionally, dialysis CKD patients also had a higher incidence of angiodysplasia bleeding compared to dialysis-free CKD patients and control subjects (1.1% vs. 0.1% and 0.1%, respectively; both < 0.001). Multivariate analysis showed that extreme old age (age ≥ 85), male gender, dialysis-free CKD, and dialysis CKD were independent factors of lower GI bleeding. Additionally, dialysis CKD patients also had a higher incidence of angiodysplasia bleeding compared to dialysis-free CKD patients and control subjects (1.1% vs. 0.1% and 0.1%, respectively; both.

Conclusion: Hemodialysis may have higher risk of lower GI bleeding and angiodysplasia bleeding.
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http://dx.doi.org/10.1155/2020/7206171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072111PMC
March 2020

Jdp2-deficient granule cell progenitors in the cerebellum are resistant to ROS-mediated apoptosis through xCT/Slc7a11 activation.

Sci Rep 2020 03 18;10(1):4933. Epub 2020 Mar 18.

Graduate Institute of Medicine, Kaohsiung Medical University, 80708, Kaohsiung, Taiwan (R.O.C.).

The Jun dimerization protein 2 (Jdp2) is expressed predominantly in granule cell progenitors (GCPs) in the cerebellum, as was shown in Jdp2-promoter-Cre transgenic mice. Cerebellum of Jdp2-knockout (KO) mice contains lower number of Atoh-1 positive GCPs than WT. Primary cultures of GCPs from Jdp2-KO mice at postnatal day 5 were more resistant to apoptosis than GCPs from wild-type mice. In Jdp2-KO GCPs, the levels of both the glutamate‒cystine exchanger Sc7a11 and glutathione were increased; by contrast, the activity of reactive oxygen species (ROS) was decreased; these changes confer resistance to ROS-mediated apoptosis. In the absence of Jdp2, a complex of the cyclin-dependent kinase inhibitor 1 (p21) and Nrf2 bound to antioxidant response elements of the Slc7a11 promoter and provide redox control to block ROS-mediated apoptosis. These findings suggest that an interplay between Jdp2, Nrf2, and p21 regulates the GCP apoptosis, which is one of critical events for normal development of the cerebellum.
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http://dx.doi.org/10.1038/s41598-020-61692-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080836PMC
March 2020

Equivalent efficacies of reverse hybrid and concomitant therapies in first-line treatment of Helicobacter pylori infection.

J Gastroenterol Hepatol 2020 Oct 31;35(10):1731-1737. Epub 2020 Mar 31.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.

Background And Aim: Concomitant therapy is a recommended first-line treatment for Helicobacter pylori infection in most national or international consensuses. Reverse hybrid therapy is a modified 14-day concomitant therapy without clarithromycin and metronidazole in the final 7 days. This study aims to test whether 14-day reverse hybrid therapy is non-inferior to 14-day concomitant therapy in the first-line treatment of H. pylori infection.

Methods: Helicobacter pylori-infected adult patients were randomly assigned to receive either reverse hybrid therapy (dexlansoprazole 60 mg o.d. plus amoxicillin 1 g b.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.d. for initial 7 days) or concomitant therapy (dexlansoprazole 60 mg once o.d. plus amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg b.d. for 14 days). H. pylori status was assessed 6 weeks after the end of treatment.

Results: Helicobacter pylori-infected participants (n = 248) were randomized to receive either 14-day reverse hybrid therapy (n = 124) or 14-day concomitant therapy (n = 124). Intention-to-treat analysis demonstrated that the two therapies had comparable eradication rate (95.2% vs 93.5%; 95% confidence interval, -4.0% to 7.4%; P = 0.582). However, reverse hybrid therapy had a much lower frequency of adverse events than concomitant therapy (20.2% vs 38.7%, P = 0.001). The two therapies exhibited comparable drug adherence (93.5% vs 87.9%, P = 0.125).

Conclusions: Fourteen-day reverse hybrid therapy and 14-day concomitant therapy are equivalent in efficacy for the first-line treatment of H. pylori infection. However, reverse hybrid therapy has fewer adverse events compared with concomitant therapy.
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http://dx.doi.org/10.1111/jgh.15034DOI Listing
October 2020

Reverse hybrid therapy achieves a similar eradication rate as standard hybrid therapy for Helicobacter pylori infection.

J Chin Med Assoc 2020 Mar;83(3):233-237

Division of Gastroenterology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, ROC.

Background: Reverse hybrid therapy is a simplified hybrid treatment for Helicobacter pylori infection. It achieves a higher eradication rate than standard triple therapy. This study aimed to compare the efficacies of reverse hybrid and hybrid therapies in the treatment of H. pylori infection.

Methods: From September 2008 to September 2017, 490 H. pylori-infected patients who received 14 days of reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the initial 7 days; n = 252) or hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the final 7 days; n = 238) were included in this retrospective cohort study. Helicobacter pylori status was examined 6-8 weeks after therapy.

Results: The eradication rates of the reverse hybrid and hybrid therapies by modified intention-to-treat analysis were comparable (96.4% vs 96.6%; p = 0.899). There were no differences in the efficacy of eradication between therapies for clarithromycin-resistant strains (87.0% vs 90.0%) or metronidazole-resistant strains (97.7% vs 100.0%). In addition, there were comparable frequencies of adverse events for both treatments (18.7% vs 13.0%) and treatment adherence (94.4% vs 97.1%).

Conclusion: Reverse hybrid therapy can achieve a similar eradication rate to hybrid therapy for H. pylori infection.
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http://dx.doi.org/10.1097/JCMA.0000000000000256DOI Listing
March 2020

Development and Validation of the Asia-Pacific Proximal Colon Neoplasia Risk Score.

Clin Gastroenterol Hepatol 2021 Jan 7;19(1):119-127.e1. Epub 2020 Jan 7.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong; The Institute of Digestive Disease, The Chinese University of Hong Kong; The State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Background & Aims: Patients found to be at high risk of advanced proximal neoplasia (APN) after flexible sigmoidoscopy screening should be considered for colonoscopy examination. We developed and validated a scoring system to identify persons at risk for APN.

Methods: We collected data from 7954 asymptomatic subjects (age, 50-75 y) who received screening colonoscopy examinations at 14 sites in Asia. We randomly assigned 5303 subjects to the derivation cohort and the remaining 2651 to the validation cohort. We collected data from the derivation cohort on age, sex, family history of colorectal cancer, smoking, drinking, body mass index, medical conditions, and use of nonsteroidal anti-inflammatory drugs or aspirin. Associations between the colonoscopic findings of APN and each risk factor were examined using the Pearson χ test, and we assigned each participant a risk score (0-15), with scores of 0 to 3 as average risk and scores of 4 or higher as high risk. The scoring system was tested in the validation cohort. We used the Cochran-Armitage test of trend to compare the prevalence of APN among subjects in each group.

Results: In the validation cohort, 79.5% of patients were classified as average risk and 20.5% were classified as high risk. The prevalence of APN in the average-risk group was 1.9% and in the high-risk group was 9.4% (adjusted relative risk, 5.08; 95% CI, 3.38-7.62; P < .001). The score included age (61-70 y, 3; ≥70 y, 4), smoking habits (current/past, 2), family history of colorectal cancer (present in a first-degree relative, 2), and the presence of neoplasia in the distal colorectum (nonadvanced adenoma 5-9 mm, 2; advanced neoplasia, 7). The c-statistic of the score was 0.74 (95% CI, 0.68-0.79), and for distal findings alone was 0.67 (95% CI, 0.60-0.74). The Hosmer-Lemeshow goodness-of-fit test statistic was greater than 0.05, indicating the reliability of the validation set. The number needed to refer was 11 (95% CI, 10-13), and the number needed to screen was 15 (95% CI, 12-17).

Conclusions: We developed and validated a scoring system to identify persons at risk for APN. Screening participants who undergo flexible sigmoidoscopy screening with a score of 4 points or higher should undergo colonoscopy evaluation.
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http://dx.doi.org/10.1016/j.cgh.2019.12.031DOI Listing
January 2021

Taiwan nutritional consensus on the nutrition management for gastric cancer patients receiving gastrectomy.

J Formos Med Assoc 2021 Jan 16;120(1 Pt 1):25-33. Epub 2019 Dec 16.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. Electronic address:

Currently, consensus reports on the nutritional management for gastric cancer patients receiving gastric resection are lacking. The Gastroenterological Society of Taiwan therefore organized the Taiwan Gastric Cancer Nutritional Consensus Team to provide an overview of evidence and recommendations on nutritional support for gastric cancer patients undergoing gastrectomy. This consensus statement on the nutritional support for gastric cancer patients has two major sections:(1)perioperative nutritional support; and (2)long-term postoperative nutritional care. Thirty Taiwan medical experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. The key statements included that preoperative nutritional status affects the incidence of operative complications and disease-specific survival in gastric cancer patients undergoing gastrectomy. Following gastrectomy, both early oral and enteral tube feeding can result in a shorter stay than total parenteral nutrition. Compared to late oral feeding, early oral feeding can reduce hospital stay in gastric cancer patients receiving gastrectomy without an increase in complication rate. Routine supplementation with vitamin B is indicated for gastric cancer patients undergoing a total gastrectomy. Both high-dose oral vitamin B supplementation and intramuscular administration of vitamin B are equally effective in the treatment of vitamin B deficiency.
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http://dx.doi.org/10.1016/j.jfma.2019.11.014DOI Listing
January 2021

Analysis of Oxidative and Advanced Oxidative Modifications in Hemoglobin of Oral Cancer Patients by Mass Spectrometry.

Anal Chem 2020 01 11;92(1):724-731. Epub 2019 Dec 11.

Department of Chemistry and Biochemistry , National Chung Cheng University , 168 University Road , Ming-Hsiung, Chia-Yi 62142 , Taiwan.

We are exposed to endogenous reactive oxygen species (ROS) produced during normal aerobic metabolism and by the innate immune systems. Excessive production of ROS is critically important in disease onset and progression. Post-translational oxidative modifications of hemoglobin have been used as a surrogate biomarker for monitoring the oxidative stress in vivo. In this study, the Fenton reaction was used as a model to produce ROS and react with human hemoglobin. After trypsin digestion, the types and sites of modifications were characterized by a nanoflow LC-nanoelectrospray ionization high-resolution mass spectrometer. Besides oxidation at certain sites of Met, His, and Tyr, conversion of histidine to aspartate and hydroxyaspartate was identified at four sites. Furthermore, advanced oxidation of histidine to hydroxyaspartate was identified at two sites. Elevated oxidative stress is tightly associated with oral cancer. The relative extent of modification at the identified sites was quantified relative to the native peptide present in the digest as the reference peptide in hemoglobin from 18 oral cancer patients and 15 healthy control subjects. The results revealed that the extents of oxidation at β-His-77 and β-Asp-99 of globin were significantly elevated in oral cancer patients compared to healthy subjects, while the extents of conversion of histidine residues at α-His-20, α-His-50, and β-His-2 to aspartate were significantly decreased. Furthermore, the advanced oxidation of histidine to hydroxyaspartate at α-His-50 and β-His-2 is also significantly higher in oral cancer patients than in healthy subjects ( < 0.05). To our knowledge, this advanced oxidation of histidine to hydroxyaspartate is a new post-translational protein modification, and it is found in human hemoglobin isolated from blood. This advanced oxidative modification in hemoglobin might be a potential biomarker to assess oxidative stress in oral cancer patients.
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http://dx.doi.org/10.1021/acs.analchem.9b02743DOI Listing
January 2020

Nutritional and dietary strategy in the clinical care of inflammatory bowel disease.

J Formos Med Assoc 2020 Dec 14;119(12):1742-1749. Epub 2019 Oct 14.

Department of Gastroenterology, Chang-Hua Christian Hospital, Changhua, Taiwan. Electronic address:

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.
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http://dx.doi.org/10.1016/j.jfma.2019.09.005DOI Listing
December 2020

A comparison between dexlansoprazole modified release-based and lansoprazole-based nonbismuth quadruple (concomitant) therapy for first-line eradication: a prospective randomized trial.

Infect Drug Resist 2019 16;12:2923-2931. Epub 2019 Sep 16.

Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Purpose: Steadily maintaining high intra-gastric PH is the major factor for successful eradication. It is important to search for a stronger PPI. Dexlansoprazole MR is a dual delayed release formulation PPI taken once daily which is capable of maintaining longer duration of high intra-gastric PH. It is very effective in treating gastroesophageal disease but reports on eradication is very rare. This study sought to compare dexlansoprazole MR-based concomitant treatment and lansoprazole-based concomitant treatment in infection and to investigate the factors that affect the eradication rates.

Methods: Two hundred two participants with infection were included and randomly assigned to seven days of dexlansoprazole MR-based concomitant therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily; DACM group) or a seven days of lansoprazole-based concomitant therapy (lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and metronidazole 500 mg twice daily; LACM group). The participants were asked to perform urea breath tests eight weeks later.

Results: The eradication rates in the DACM group were 86.1% [95% confidence interval (CI): 77.8%-92.2%] in the ITT analysis and 90.6% (95% CI: 82.9%-95.6%) in the PP analysis, respectively, as compared with 90.1% (95% CI: 82.6%-95.2%) and 92.6% (95% CI: 85.5%-96.9%) (=0.384 and =0.572, respectively) in the LACM group for the same analyses. The adverse event rates were 11.5% in the DACM group and 10.2% in the LACM group (=0.779).

Conclusion: As a first-line treatment regimen, dexlansoprazole MR-based concomitant therapy attained a successful eradication rate of 90%, which was non inferior to that of lansoprazole-based concomitant treatment.

Clinicaltrialsgov Identifier: NCT03829150.
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http://dx.doi.org/10.2147/IDR.S213998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754331PMC
September 2019

Preclinical evaluation of exemestane as a novel chemotherapy for gastric cancer.

J Cell Mol Med 2019 11 26;23(11):7417-7426. Epub 2019 Sep 26.

Department of Gastroenterology, Chinese Medicine Research and Development Center, Sex Hormone Research Center, Research Center for Tumor Medicine, China Medical University Hospital, Taichung, Taiwan.

CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single-cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian-based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5-Fluorouracil (5-FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar-targeting compounds were tested, and the results showed that exemestane exhibited superior cancer-suppressing efficacy to other ARIs. In addition, exemestane down-regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5-FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose-dependent manner. Combining subminimal doses of 5-FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5-FU and exemestane for GCa therapy is recommended.
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http://dx.doi.org/10.1111/jcmm.14605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815818PMC
November 2019

Analysis of cysteine glutathionylation in hemoglobin of gastric cancer patients using nanoflow liquid chromatography/triple-stage mass spectrometry.

Rapid Commun Mass Spectrom 2020 Apr 5;34 Suppl 1:e8588. Epub 2020 Feb 5.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Glutathione is an intracellular antioxidant capable of scavenging free radicals and detoxifying electrophiles from endogenous and exogenous sources via the free thiol group. Post-translational glutathionylation at cysteine residues of proteins can affect the structure and cause a functional change of proteins. Protein glutathionylation has been proven to reflect the cellular redox status. Our previous report indicates that the levels of glutathionylation in hemoglobin from peripheral blood of smokers are significantly higher than in nonsmokers. In this study, a nanoflow liquid chromatography/nanospray ionization triple-stage mass spectrometric (nanoLC/NSI-MS ) method with a linear ion trap mass spectrometer was employed to quantify glutathionylated peptides in the trypsin digests of hemoglobin from gastric cancer patients. We compare the extent of glutathionylation in hemoglobin from nonsmoking gastric cancer patients with that from nonsmoking healthy adults. Using a carboxymethylated peptide as the reference peptide, the relative quantification of each glutathionylated peptide was measured as the peak area ratio of the modified peptide versus the sum of the peak areas of the modified and the carboxymethylated parent peptide in the selected reaction monitoring chromatograms. Using this method, we found that the extents of glutathionylation at Cys-104 of the α-globin and Cys-93 of β-globulin hemoglobin from 10 gastric cancer patients were significantly higher than those from 14 normal individuals with p values <0.0001. Our results suggest the possibility of using the extent of cysteine glutathionylation at β-93 of hemoglobin as an oxidative stress biomarker candidate for gastric cancer.
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http://dx.doi.org/10.1002/rcm.8588DOI Listing
April 2020

Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis.

Oncogene 2019 09 22;38(37):6461-6477. Epub 2019 Jul 22.

Center for Neuroscience, National Sun Yat-Sen University, Kaohsiung, Taiwan.

Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.
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http://dx.doi.org/10.1038/s41388-019-0886-3DOI Listing
September 2019

Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series.

Kaohsiung J Med Sci 2019 Sep 14;35(9):566-571. Epub 2019 Jun 14.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.
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http://dx.doi.org/10.1002/kjm2.12094DOI Listing
September 2019