Volume 31 Issue 8 - April 27, 2018 PDF
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H. pylori study in NCKU and overcome difficult-issues of digestive tract
Department of Medicine, College of Medicine, National Cheng Kung University
 
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【106 MOST Outstanding Research Award】Special Issue

Prof. Bor-Shyang Sheu has a central belief: clinical research is to “improve the need of patients”. Prof. Sheu has been nominated as Distinguished Professor of NCKU since 2007, and as chairman of Internal medicine Committee of National Science Council, ROC 2011-2013. Prof. Sheu also served as deputy superintendent in NCKU hospital in 2011-2015. Prof. Sheu is now served as superintendent of Tainan Hospital, Ministry of Health & Welfare, due to the co-promotion with NCKU hospital. Prof. Sheu’s achievements are categorized in 4 aspects:

1> H. pylori virulence for gastric colonization- vaccination target beneath gastric mucin gel

Colonization of H. pylori to the gastric epithelium is the first step to establish infection. Our team explored two putative pathways for colonization (Figure 1): 1> the interaction between gastric Lewis B on epithelium and BabA of bacteria (2003, Gut), and 2> while host lack or shortage with Lewis B antigen, between sialyl-Lewis X and SabA of bacteria (2006, Am J Gastroenterol). Prof. Sheu was award as “Emerging Leader Lectureship” on 2009 Asia-Pacific Digestive Week, for milestone contribution to define H. pylori vaccination targets (2010, JGH).
Figure 1. The colonization of H. pylori beneath gastric mucin gel.

2> H. pylori virulence for gastric carcinogenesis- a bug-medicated high-pH vicious cycle

H. pylori is type I WHO carcinogen, our team discovered H. pylori cagL amino-acid sequence in as Y58/E59 can mediate a stronger binding to the integrin α5β1 receptor of gastric epithelium and facilitate type IV secretion system (T4SS) to inject H. pylori CagA into cells to trigger up adverse carcinogenetic cascade. During chronic H. pylori infection, an achlorhydria environment can prime up integrin α5β1 receptor to adapt with CagL-Y58E59 with a vicious cycle (Figure 2). Screening out the high virulent H. pylori or adjust the intra-gastric environment can stop the vicious cycle to improve gastric cancer control (2013, PLoS ONE).
Figure 2. The achlorhydria vicious cycle of H. pylori to gastric carcinogenesis.

3> Screening and long-term surveillance to H. pylori-related precancerous lesions

Intestinal metaplasia (IM) is an important precancerous lesion of H. pylori infection. It is too late to eradicate H. pylori for gastric cancer control, once IM has developed. Prof. Sheu’s team composed a novel histological marker as corpus-predominant gastritis index (CGI), earlier marker than IM to identify out high-risk group for early H. pylori eradication (2013, APT). Moreover, our team conducted screening and long-term surveillance for risky IM in H. pylori-infected subjects with chemoprevention to reverse the IM progression since 2003 until now. Our team shall be highly original to illustrate 70% IM cases have persisted IM with COX-2 overexpression, despite of H. pylori eradication (2003, Clin Cancer Res). Because a better IM regression by H. pylori eradication in the long-term COX-2 inhibitor user (2007, APT), Prof. Sheu conducted clinical trial (2014, Helicobacter) to suggest COX-2 inhibitor can be safe to prevent IM progression after H. pylori eradication. Prof. Sheu composed the 1st Taiwan national-wide H. pylori consensus to highlight successful Taiwan experience for globalization (2017, Helicobacter).

4> The breakthroughs to difficult clinical issues of upper gastrointestinal diseases

4-1 Upper gastrointestinal bleeding (UGIB)
Upper gastrointestinal bleeding is a fatal clinical disease, especially in senile comorbid background. Our team is novel to illustrate double oral dose of PPI can be highly cost-beneficial to achieve well control of rebleeing for high risky patients with Rockall scores > 6 comorbid illness (2014, Gut). The study has breakthrough contribution to offer the optimal dosage and duration of PPI to improve the recurrent bleeding control in such risky patient. The cornerstone results were included in UGIB guideline in USA and in Taiwan.

4-2 Gastroesophageal reflux disease (GERD)
GERD is an important clinical burden worldwide in need to improve refractory case control. Prof. Sheu disclosed higher body mass index (BMI > 25 kg/m2) is an independent factor to determine PPI response in Grade AB & CD cases (2007 & 2008, Am J Gastroenterol). Prof. Sheu illustrated double-dosed PPI can improve the GERD control for overweight and obesity (2010, Am J Gastroenterol). Prof. Sheu also suggested to eradicate H. pylori infection to prevent progression of precancerous lesion during long-term PPI for GERD (2009, Am J Gastroenterol).  Herein, Prof. Sheu was invited to compose the national Taiwan GERD consensus on 2014.

Awardee remarks:Research is to find, to face, to resolve the problem with attitude, ability and self-refreshment. Based on the lucky support with good logistics, persistent motivation, and adequate resource, I start my H. pylori journey in NCKU. I appreciate all the events happen to me, including both positive vs. negative, even though the latter seems to be more. I shall keep “Patient is my best research teacher” with this late coming honor. There will be no change in my consistent persistence to research on tomorrow’s sun rise. By this way, I express my deep appreciation to my wife to let me “always believe there will be unlimited possibility in life”.

References:
  1. Sheu BS, Sheu SM, Yang HB, Huang AH, Wu JJ*. Host gastric Lewis expressions determine the bacterial density of babA2-genopositve H. pylori infection. Gut 2003;50:927-32
  2. Sheu BS*, Kao AW, Cheng HC, Yang HB, Hung KH, Liou CP, Wu JJ. Interaction of sialyl-Lex and SabA of Helicobacter pylori on the bacterial density of clinical patients lacking the gastric Lewis B expression. Am J Gastroenterol 2006;101:36-44
  3. Sheu BS*, Yang HB, Yeh YC, Wu JJ. Helicobacter pylori colonization of the human gastric epithelium: a bug's first step is a novel target for us. J Gastroenterol Hepatol 2010;25:26-32
  4. Yeh YC, Cheng HC, Yang HB, Chang WL, Sheu BS*. H. pylori CagL-Y58/E59 prime higher integrin α5β1 in adverse pH condition to enhance hypochlorhydria vicious cycle for gastric carcinogenesis. PLoS One. 2013; 8:e72735
  5. Sheu BS*, Yang HB, Sheu SM, Huang AH, Wu JJ. Higher gastric COX-2 expression and precancerous changes in the relatives of H. pylori-infected gastric cancer. Clin Cancer Res 2003;9:5245-51
  6. Yang HB, Cheng HC, Sheu BS*, Hung KH, Liou MF, Wu JJ. Chronic celecoxib users more often show regression of gastric intestinal metaplasia after H. pylori eradication. Aliment Pharmacol Ther 2007;25:455-61
  7. Sheu BS*, Tsai YC, Wu CT, Chang WL, Cheng HC, Yang HB. Long-term celecoxib can prevent the progression of persistent gastric intestinal metaplasia after H. pylori eradication. Helicobacter 2013;18:117-23HP
  8. 8.Sheu BS, Wu MS, Chiu CT, Lo JC, Wu DC, Liou JM, Wu CY, Cheng HC, Lee YC, Hsu PI, Chang CC, Chang WL, Lin JT. Consensus on the clinical management, screening-to-treat, and surveillance of H. pylori infection to improve gastric cancer control on a nationwide scale. Helicobacter 2017; 22 doi: 10.1111/hel.12368
  9. Tsai YC, Hsiao WH, Yang HB, Cheng HC, Chang WL, Lu CC, Sheu BS*. The corpus- predominant gastritis index (CGI) may serve as an early marker of Helicobacter pylori-infected patients at risk of gastric cancer. Aliment Pharmacol Ther 2013; 37:969-78
  10. Cheng HC, Wu CT, Chang WL, Cheng WC, Chen WY, Sheu BS*. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut 2014; 63:1864-72
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