Publications by authors named "Wen-Hung Hsu"

58 Publications

Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis.

Pharmaceuticals (Basel) 2021 Mar 14;14(3). Epub 2021 Mar 14.

Department of Orthopedics, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 40201, Taiwan.

Timosaponin AIII (TSAIII) is a steroidal saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal F-actin and cytoskeletal-related proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis. In the synergistic inhibitory analysis, cotreatment of TSAIII with αVβ3 integrin inhibitor [Cyclo(RGDyK)] or focal adhesion kinase (FAK) inhibitor (PF-573228) exerted greater synergistic inhibitory effects on the expression of Intergin αVβ3/FAK/cofilin axis, thus inhibiting the migration and invasion capacities of human osteosarcoma cells. TSAIII was demonstrated to significantly inhibit the pulmonary metastasis formation of human osteosarcoma cells in vivo in metastasis animal models. These findings reveal the inhibitory effects of TSAIII on the metastasis progression of human osteosarcoma cells and the regulation of integrin-αVβ3-FAK-Src and TESK1/p-cofilin mediated cytoskeletal F-actin pathway. Therefore, TSAIII might represent a novel strategy for the auxiliary treatment of human osteosarcoma cells.
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http://dx.doi.org/10.3390/ph14030260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000016PMC
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

Endoscopic Surveillance for Metachronous Esophageal Squamous Cell Neoplasms among Head and Neck Cancer Patients.

Cancers (Basel) 2020 Dec 18;12(12). Epub 2020 Dec 18.

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

Esophageal squamous cell neoplasms (ESCNs) are the most common second primary neoplasm in patients with head and neck squamous cell carcinoma (HNSCC), and few studies have focused on metachronous ESCNs. We aimed to evaluate the incidence of and risk factors for metachronous ESCNs and to provide a reasonable endoscopic follow-up plan for HNSCC patients. We extended our prospective cohort since October 2008 by recruiting incident HNSCC patients. All enrolled patients were interviewed to collect information on substance use (smoking, alcohol, and betel nut) and esophagogastroduodenoscopy (EGD) with Lugol chromoendoscopy results for synchronous ESCNs soon after HNSCC diagnosis. Endoscopic screenings for metachronous ESCNs were performed 6 to 12 months after the previous examinations. A total of 1042 incident HNSCC patients were enrolled, but only 175 patients met all the criteria and were analyzed. A total of 20 patients had metachronous ESCNs (20/175, 11.4%). Only the initial Lugol-voiding lesion (LVL) classification significantly predicted the development of metachronous ESCNs. Patients with an LVL classification of C/D had a higher risk of developing metachronous ESCNs than those with an LVL classification of A/B (adjusted odds ratio: 5.03, 95% confidence interval: 1.52-16.67). The mean interval for developing metachronous ESCNs was 33 months, but the shortest interval for developing metachronous esophageal squamous cell carcinoma was 12 months. Lugol chromoendoscopy screening among incident HNSCC patients predicts the risk of developing metachronous ESCNs. A closer follow-up with an endoscopy every 6 months is recommended for those with LVL classifications of C and D.
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http://dx.doi.org/10.3390/cancers12123832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766780PMC
December 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

Prognostic Value of EGFR Expression for Patients with Stage III Colorectal Cancer Receiving Fluoropyrimidine Metronomic Maintenance Therapy After Radical Resection and Adjuvant Oxaliplatin-Based Chemotherapy.

Oncol Res 2020 Aug 28. Epub 2020 Aug 28.

This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy with oral capecitabine (daily dose of 850 mg/m2, twice daily, on days 1-14 days every 3 weeks for 6 months) on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockout of the EGFR gene, we analyzed the capacities of cell proliferation and migration. Relapse and survival were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent associated factor of relapse and survival as well as a prognostic factor of disease-free survival and overall survival. Significant intergroup differences in survival were only observed in patients with positive EGFR expression. Thus, our findings suggest EGFR expression is a prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. Analysis of EGFR expression in these patients helps identify potential candidates who may receive the optimal survival benefit from metronomic maintenance therapy.
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http://dx.doi.org/10.3727/096504020X15986099915822DOI Listing
August 2020

Effect of and mutations on the prognosis of patients with synchronous metastatic colorectal cancer presenting with liver-only and lung-only metastases.

Oncol Lett 2020 Sep 1;20(3):2119-2130. Epub 2020 Jul 1.

Department of Surgery, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.

It has been reported that 20-25% of patients with colorectal cancer (CRC) have metastases at the time of diagnosis. Liver and lung are the most common metastatic sites. The aim of the present study was to investigate the association of and mutations with clinicopathological features and prognosis of patients with initial liver-metastasis only (LiM-only) or lung-metastasis only (LuM-only) metastatic CRC (mCRC). Overall, 166 patients with CRC with initial LiM-only (n=124) and LuM-only (n=42) were retrospectively analyzed from January 2014 to December 2017. The median follow-up time was 19.2 months (1.0-57.1 months). Patient characteristics at diagnosis were collected. Genomic DNA was isolated from frozen primary CRC tissues for targeting and . Patients with LuM-only were significantly older compared with those with LiM-only (65.5 vs. 61.5 years; P=0.05). There was no significant differences between the LiM-only and LuM-only groups in terms of sex, location of the primary tumor, serum carcinoembryonic antigen level, histological grade and mutation status. mutations were detected in 43 (41.0%) patients with LiM-only and 13 (35.1%) patients with LuM-only. The overall survival time (OS) of LuM-only was more favorable compared with that of patients with LiM-only (44.5 vs. 24.7 months); however, there was no significant difference (P=0.095). The progression-free survival (PFS) and OS in the wild-type group were significantly improved compared with the mutant cohorts (P=0.004 and P=0.031, respectively) in the LiM-only group. In patients with stage IV CRC, those with synchronous LiM-only mCRC had a higher incidence of metastasis but a less favorable PFS and OS compared with patients with LuM-only. mutation status exhibited a significant association with the survival outcome in patients with LiM-only mCRC.
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http://dx.doi.org/10.3892/ol.2020.11795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400335PMC
September 2020

Endoscopic management of strictures in patients with Crohn's disease - A multi-center experience in Taiwan.

J Formos Med Assoc 2020 Oct 6;119(10):1500-1505. Epub 2020 Jan 6.

Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; MacKay Medical College, New Taipei City, Taiwan. Electronic address:

Background/purpose: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) disorder that causes relapsing inflammation and severe mucosal damage in the intestine. Crohn's disease (CD)-related stricturing complications are a major cause of surgery, disability, and reduced quality of life. Endoscopic balloon dilation (EBD) has been shown to reliably delay or prevent surgery in patients with stricturing CD. However, cases of EBD performed for stricture in CD in Taiwan are rare. In this study, we want to evaluate the experiences regarding EBD for stricturing CD in Taiwan.

Methods: We conducted a retrospective analysis of 9 medical centers in Taiwan. Patients with CD-related strictures who were treated with EBD were included and analyzed.

Results: In nine medical centers, a total of 26 CD patients (19 male, 7 female, mean disease duration 75.4 ± 65.2 months) underwent 42 EBD procedures during the study period. Among the subjects, an 83.3% (35/42) EBD success rate was seen, but 26.9% (7/26) patients underwent surgery after ineffective EBD. In the surgery group, the the small bowel strictures was high compared with the non-surgery group (p = 0.01). There were no significant differences in disease phenotype, disease duration or history of fistulizing disease. In the surgery group, immunosuppressant use was high, and 5-aminosalicylic acid (5-ASA) use was low compared with the non-surgery group. After EBD, the physicians tended to change the drugs, especially increasing the use of biologic agents.

Conclusion: EBD is a safe and effective procedure for CD-related stricture, with a 83.3% success rate in Taiwan.
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http://dx.doi.org/10.1016/j.jfma.2019.12.005DOI Listing
October 2020

Metastasis-associated protein 2 regulates human hepatocellular carcinoma metastasis progression through modulating p38MAPK/MMP2 pathways.

J Cancer 2019 22;10(26):6716-6725. Epub 2019 Oct 22.

Institute of Biochemistry, Microbiology, and Immunology, Chung Shan Medical University, Taichung, Taiwan.

Studies have shown the overexpression of metastasis-associated protein 2 (MTA2) to be associated with hepatocellular carcinoma (HCC) progression. However, the molecular mechanism of MTA2 expression in HCC is unclear. In our study, we found a higher level of MTA2 in HCC tissues than in normal tissues and a significant correlation between tumor grade and overall survival of HCC patients. We also found that MTA2 inhibition reduced the migration and invasion capabilities of HCC cells, independent of cell proliferation. Mechanistic studies have suggested that MTA2 protein and mRNA are more highly expressed in SK-Hep-1 and Huh-7 cells compared with other HCC cells. MTA2 silencing drastically reduced migration and invasion capability and also inhibited matrix metalloproteinase 2 (MMP2) at the transcriptional and translation levels in both cells. In addition, treatment with the MMP2 antibody markedly impaired MTA2-knockdown-mediated inhibition of migration and invasion in SK-Hep-1 cells. Furthermore, MTA2 knockdown reduced the phosphorylation of the p38MAPK protein, whereas the inhibition of p38MAPK (SB203580 or si-p38) confirmed that blocking the p38MAPK pathway mediated MTA2-knockdown-inhibited migration and invasion in SK-Hep-1 cells. We demonstrated the molecular mechanism by which MTA2 inhibits human HCC cell metastasis through the p38MAPK/MMP2 pathways, which might be helpful in determining the diagnostic value of this protein in patients with HCC.
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http://dx.doi.org/10.7150/jca.35626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856896PMC
October 2019

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

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

Current applications of fecal microbiota transplantation in intestinal disorders.

Kaohsiung J Med Sci 2019 Jun 24;35(6):327-331. Epub 2019 Apr 24.

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

Fecal microbiota transplantation (FMT) had been an ancient remedy for severe illness several centuries ago. Under modern medical analysis and evidence-based research, it has been proved as an alternative treatment for recurrent Clostridium difficile infection and recent randomized control study also showed that FMT could be an adjuvant treatment for inflammatory bowel disease. As we get a better understanding of the relationship between gut microbiota and systemic disease, FMT became a potential treatment to explore. This article summarized procedures such as donor selection, fecal material preparation, transplantation delivery methods, and adverse events. We also review the present evidence about FMT in clinical practice.
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http://dx.doi.org/10.1002/kjm2.12069DOI Listing
June 2019

Postendoscopic retrograde cholangiopancreatography pancreatitis.

Kaohsiung J Med Sci 2019 Apr 19;35(4):195-201. Epub 2019 Mar 19.

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

Endoscopic retrograde cholangiopancreatography (ERCP) has been a mainstay examination to clarify the biliary and pancreatic system. Not just diagnostic purpose, it could achieve therapeutic goal. Under the trend of more and more procedures about ERCP being interventional, the rate of adverse events after the procedure is increasing. Among them, post-ERCP pancreatitis (PEP) is the most common and sometimes tremendous complication. This mini-review will overview the PEP from definition, pathogenesis, and risk factors to prevention.
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http://dx.doi.org/10.1002/kjm2.12040DOI Listing
April 2019

Gastric juice-based PCR assay: An alternative testing method to aid in the management of previously treated Helicobacter pylori infection.

Helicobacter 2019 Apr 28;24(2):e12568. Epub 2019 Feb 28.

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

Background: Culture of Helicobacter pylori with previous eradication failure has been emphasized in clinical guidelines. The current unmet need to manage previously treated H pylori is one tool with diagnostic accuracy and ability for antibiotics susceptibility. Gastric juice PCR can provide diagnosis and antibiotics susceptibility; however, whether treatment failure affects its accuracy remains uninvestigated. Our study aimed to investigate diagnostic accuracy and antibiotics susceptibility of juice PCR in previously treated H pylori and to compare with the current standard of culture.

Methods: We categorized all 547 patients into treatment-naïve, post-1st treatment, post-2nd treatment, and post-3rd treatment. Helicobacter pylori infection was confirmed using gold standards. Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under ROC curve (AUC) of juice PCR and culture were calculated. Intra-gastric H pylori density was evaluated. Lastly, the antibiotics susceptibility results of gastric juice and culture were compared.

Results: Our findings demonstrated AUC was higher in juice PCR than culture in all patients (96.7% vs 91.3%, P < 0.0001). The superiority of juice PCR was statistically significant in previously treated patients (P < 0.0001) but not in treatment-naïve patients (P = 0.13). Antral H pylori density was less marked in previously treated patients (P = 0.014). The comparisons of PCR-RFLP and E-test for Clarithromycin resistance showed reliable AUC = 89.8%.

Conclusion: Compared with the current standard of culture, the gastric juice PCR contains the strengths of performing the antibiotics susceptibility and overcomes the shortcomings of low accuracy. Consequently, gastric juice PCR suits the unmet need to manage previously treated H pylori.
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http://dx.doi.org/10.1111/hel.12568DOI Listing
April 2019

Predictor of slower gastric emptying in gastroesophageal reflux disease: Survey of an Asian-Pacific cohort.

J Gastroenterol Hepatol 2019 May 15;34(5):837-842. Epub 2019 Jan 15.

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

Background And Aim: Asian populations have relatively lower prevalence of gastroesophageal reflux disease and tend to exhibit symptoms of prolonged gastric retention. However, it remains unknown if slower gastric emptying influences its features in Asian countries. We prospectively assessed the potential implications of slower gastric emptying in an Asian-Pacific cohort of gastroesophageal reflux disease by a hospital-based survey.

Methods: One hundred fifty-two patients of gastroesophageal reflux disease complete the scintigraphic measurement of solid phase of gastric emptying. Clinical symptoms and psychological stress are recorded by self-report questionnaire. The status of Helicobacter pylori infection, blood level of pepsinogen I, and I/II ratio are assessed.

Results: Forty-seven percent and 28% of the patients have slower gastric emptying rate, depending on the incremental defined cut-off values of slower gastric emptying, respectively. Multiple logistic regression analysis indicates that older age and depression score are independently related to slower gastric emptying. Subgroup analysis discloses that patients with slower gastric emptying and higher depression score tend to present with non-erosive esophagitis whereas higher body mass index level and male gender in patients with normal gastric emptying predict the presence of erosive reflux disease.

Conclusions: Our study cohort of Asian patients indicates distinctive clinical implications of slower gastric emptying in patients with gastroesophageal reflux disease.
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http://dx.doi.org/10.1111/jgh.14572DOI Listing
May 2019

Helicobacter pylori Infection-Induced Hepatoma-Derived Growth Factor Regulates the Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells.

Cancers (Basel) 2018 Nov 30;10(12). Epub 2018 Nov 30.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tz-You 1st road, Kaohsiung 807, Taiwan.

Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. () infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer. Carcinoma-associated fibroblasts (CAFs) are myofibroblasts in tumor microenvironment, which possess various abilities to promote the progression of cancer by stimulating neoangiogenesis, proliferation, migration, invasion and therapy resistance of tumor cell. Mesenchymal stem cells (MSCs) are reported to promote tumor malignance through differentiation of MSCs toward CAFs. In the present study, we demonstrated that infection promotes HDGF expression in human gastric cancer cells. HBMMSCs treated with HDGF assume properties of CAF-like myofibroblastic phenotypes, including expression of myofibroblast markers (α-smooth muscle actin (α-SMA), procollagen α1, tropomyoson I, desmin, fibroblast activation protein (FAP)), and fibroblast markers (prolyl-4-hydroxylase A1 (PHA1) and fibroblast specific protein-1 (FSP-1)/S100A4). HDGF recruits HBMMSCs, and then HBMMSCs further contributes to cell survival and invasive motility in human gastric cancer cells. Treatment of HDGF neutralizing antibody (HDGF-NAb) and serum significantly inhibit HDGF-regulated differentiation and recruitment of HBMMSCs. These findings suggest that HDGF might play a critical role in gastric cancer progress through stimulation of HBMMSCs differentiation to myofibroblast-like cells.
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http://dx.doi.org/10.3390/cancers10120479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316704PMC
November 2018

Licochalcone A inhibits the invasive potential of human glioma cells by targeting the MEK/ERK and ADAM9 signaling pathways.

Food Funct 2018 Dec;9(12):6196-6204

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Licochalcone A (LicA) has been reported to possess antitumor properties. However, its effect on human glioma cells remains unknown. In this study, we observed that LicA significantly suppressed the ADAM9 expression and the migration and invasion activities of human glioma cells (M059K, U-251 MG, and GBM8901) and exhibited no cell cytotoxicity. The human proteinase antibody array and immunoblot analysis indicated that the LicA treatment inhibited the expression of ADAM9 protein in human glioma cells. Recombinant human ADAM-9 (Rh-ADAM9) treatment significantly reversed the LicA-induced reduction in the ADAM9 level and the migration and invasion activities of human glioma cells. Additionally, the phosphorylation/activation of the mitogen-activated protein kinase kinase (MEK)-extracellularly responsive kinases (ERK) signaling pathway was significantly suppressed in LicA-treated human glioma cells. Cotreatment with LicA and PD98059 synergistically inhibited the ADAM9 expression, cell migration, and cell invasion, which suggested that the MEK-ERK signaling pathway was involved in the LicA-induced inhibition of the ADAM9 expression and the invasion activity of human glioma cells. These findings are the first evidence of LicA's anti-invasive properties against human glioma cells.
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http://dx.doi.org/10.1039/c8fo01643gDOI Listing
December 2018

Fecal microbiota transplantation: Review and update.

J Formos Med Assoc 2019 Mar 1;118 Suppl 1:S23-S31. Epub 2018 Sep 1.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.
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http://dx.doi.org/10.1016/j.jfma.2018.08.011DOI Listing
March 2019

Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases.

Sci Rep 2018 02 28;8(1):3821. Epub 2018 Feb 28.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, 35053, Taiwan.

Tissue stroma is known to be important in regulating Hp-mediated inflammation, but its interaction with Hp and dendritic cells (DCs) remains to be determined. To this end, the potential crosstalk between H. pylori (Hp) infected gastric stromal cells (Hp-GSCs) and DCs was investigated. Primary GSCs from cancerous and adjacent normal tissues were generated from gastric cancer patients, and monocyte-derived DCs were obtained from healthy individuals. Levels of cytokines and prostaglandin E (PGE) were measured by ELISA, and C-type lectin expression in GSCs was assessed by flow cytometry and immunohistochemistry. In a trans-well co-culture system, significantly upregulated DC-derived IL-23 expression was found when DCs were co-cultured with Hp-infected GSCs (Hp-GSCs). Further, PGE from Hp-GSCs was discovered to possess the priming effect, which could be inhibited by anti-COLEC12 (Collectin subfamily member 12) Abs, COLEC12 knockdown or when alpha3-fucosyltransferase-null (futB; HP0651) strain of Hp was used. Also, the expression of COLEC12 was co-localized with CD90 stromal cells in cancerous tissues. Hp-GSCs-conditioned DCs were able to induce the expression of IL-17 from CD4 T cells, which could be inhibited by IL-23-neutralizing Abs. These results suggested the importance of COLEC12 as a receptor involved in Hp-stromal cell interaction and its subsequent conditioning effect on DCs.
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http://dx.doi.org/10.1038/s41598-018-20957-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830506PMC
February 2018

Insights into the management of gastric antral vascular ectasia (watermelon stomach).

Therap Adv Gastroenterol 2018 14;11:1756283X17747471. Epub 2018 Jan 14.

Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tz-You 1st road, Kaohsiung 807, Taiwan.

Gastric antral vascular ectasia (GAVE) is an uncommon but important cause of chronic gastrointestinal bleeding. It is often associated with systemic diseases such as autoimmune diseases, liver cirrhosis, chronic renal insufficiency and cardiovascular disease. The etiology of GAVE has not been fully explored and remains controversial. Diagnosis is mainly based on endoscopic presentation with flat or raised erythematous stripes radiating from the pylorus to the antrum and resembles a watermelon. Clinical presentation may range from iron-deficiency anemia secondary to occult blood loss, melena to hematemesis. In past decades, many therapeutic modalities including medical, endoscopic and surgical intervention have been introduced for GAVE treatment with variable efficacy. Herein, we review the efficacy and safety of these treatment options for GAVE.
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http://dx.doi.org/10.1177/1756283X17747471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788127PMC
January 2018

A training program of a new simplified classification of magnified narrow band imaging for superficial esophageal squamous cell carcinoma.

J Gastroenterol Hepatol 2018 Jun 1;33(6):1248-1255. Epub 2018 Mar 1.

Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.

Background And Aim: Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain.

Methods: A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations.

Results: The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P < 0.05).

Conclusions: A well-designed training program can improve the diagnostic accuracy in evaluating cancer invasion depth, with substantial agreement.
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http://dx.doi.org/10.1111/jgh.14071DOI Listing
June 2018

Outcomes of limited period of adalimumab treatment in moderate to severe Crohn's disease patients: Taiwan Society of Inflammatory Bowel Disease Study.

Intest Res 2017 Oct 23;15(4):487-494. Epub 2017 Oct 23.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Background/aims: In Taiwan, due to budget limitations, the National Health Insurance only allows for a limited period of biologics use in treating moderate to severe Crohn's disease (CD). We aimed to access the outcomes of CD patients following a limited period use of biologics, specifically focusing on the relapse rate and remission duration; also the response rate to second use when applicable.

Methods: This was a multicenter, retrospective, observational study and we enrolled CD patients who had been treated with adalimumab (ADA) according to the insurance guidelines from 2009 to 2015.

Results: A total of 54 CD patients, with follow-up of more than 6 months after the withdrawal of ADA, were enrolled. The average period of treatment with ADA was 16.7±9.7 months. After discontinuing ADA, 59.3% patients suffered a clinical relapse. In the univariate analysis, the reason for withdrawal was a risk factor for relapse (=0.042). In the multivariate analysis, current smoker became an important risk factor for relapse (OR, 3.9; 95% CI, 1.2-14.8; =0.044) and male sex was another risk factor (OR, 2.9; 95% CI, 1.1-8.6; =0.049). For those 48 patients who received a second round of biologics, the clinical response was seen in 60.4%, and 1 anaphylaxis occurred.

Conclusions: Fifty-nine percent of patients experienced a relapse after discontinuing the limited period of ADA treatment, and most of them occurred within 1 year following cessation. Male sex and current smoker were risk factors for relapse. Though 60.4% of the relapse patients responded to ADA again.
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http://dx.doi.org/10.5217/ir.2017.15.4.487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683979PMC
October 2017

Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease.

Dig Dis Sci 2017 12 6;62(12):3298-3316. Epub 2017 Nov 6.

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

The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.
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http://dx.doi.org/10.1007/s10620-017-4830-5DOI Listing
December 2017

Overexpression of Endothelial Cell-Specific Molecule 1 Correlates with Gleason Score and Expression of Androgen Receptor in Prostate Carcinoma.

Int J Med Sci 2017 30;14(12):1263-1267. Epub 2017 Sep 30.

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

Endothelial cell-specific molecule 1 (ESM1) is a major prognostic marker of several tumor types, but its value as a marker for prostate cancer is unknown. The purpose of the present study was to measure the relationship of ESM1 expression with androgen receptor (AR) expression and with Gleason score in human prostate carcinoma tissue. Expression of ESM1 and AR were determined by immunohistochemical staining of prostate tissues from healthy individuals and patients with prostate cancer. The results showed that ESM1 expression was significantly higher in prostate tumor tissues than in normal prostate tissues ( < 0.01), and that ESM1 expression in prostate tumor tissue correlated with Gleason score ( < 0.016) and Gleason grade ( < 0.013). ESM1 expression was also greater in prostate tissues with higher Gleason score and Gleason grade ( < 0.001 for both comparisons), and also correlated with AR expression (R = 0.727, < 0.001). In conclusion, our results demonstrated that ESM1 should be considered as a marker for the diagnosis of prostate cancer.
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http://dx.doi.org/10.7150/ijms.21023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666560PMC
June 2018

β-mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP-2 and MMP-9 expression and activating the ERK and JNK pathways.

Environ Toxicol 2017 Nov 19;32(11):2360-2370. Epub 2017 Jul 19.

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

β-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). β-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by β-mangostin treatment in Huh-7 cells. In addition, β-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of β-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.
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http://dx.doi.org/10.1002/tox.22449DOI Listing
November 2017

Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial.

Am J Gastroenterol 2017 Sep 18;112(9):1374-1381. Epub 2017 Jul 18.

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

Objectives: Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection.

Methods: Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment.

Results: The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003).

Conclusions: Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.
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http://dx.doi.org/10.1038/ajg.2017.195DOI Listing
September 2017

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease.

Intest Res 2017 Jul 12;15(3):285-310. Epub 2017 Jun 12.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.
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http://dx.doi.org/10.5217/ir.2017.15.3.285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478754PMC
July 2017

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease.

Intest Res 2017 Jul 12;15(3):266-284. Epub 2017 Jun 12.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic mucosal inflammation of the colon, and the prevalence and incidence of UC have been steadily increasing in Taiwan. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of UC taking into account currently available evidence and the expert opinion of the committee. Accurate diagnosis of UC requires thorough clinical, endoscopic, and histological assessment and careful exclusion of differential diagnoses, particularly infectious colitis. The goals of UC therapy are to induce and maintain remission, reduce the risk of complications, and improve quality of life. As outlined in the recommended treatment algorithm, choice of treatment is dictated by severity, extent, and course of disease. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to immunosuppressive treatment, especially with steroids and biologic agents, and should be regularly monitored for reactivation of latent infection. These consensus statements are also based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of UC in Taiwan.
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http://dx.doi.org/10.5217/ir.2017.15.3.266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478753PMC
July 2017

Exploring the expression bar code of SAA variants for gastric cancer detection.

Proteomics 2017 Jun;17(11)

Department of Chemistry, National Taiwan University, Taipei, Taiwan.

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.
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http://dx.doi.org/10.1002/pmic.201600356DOI Listing
June 2017