1. How helicobacter Pylori causes gastric ulcerations and how this can be linked to cancers of the stomach By Piril Erel

2. Helicobacter Pylori 50% worlds population have Helicobacter Pylori (H. pylori) in upper gastrointestinal track2. Most people infected by H. pylori will show no symptoms1. Infects gut2. H. pylori is a gram-negative spiral shaped bacterium Detected in 19834. 3. H.pylori correlates much better with socio- economic status than race Figure 1 : A worldwide geographic demonstration which illustrates the prevalence of H.pylori around the world 4. H.pylori - The Almighty Flagella gives motility and enables the bacteria to grow under the mucosal membrane3. Lipopolysaccharides and membrane proteins adhere to host cell receptors3. Urease enzyme is used to combat the acidic environment of the stomach by producing ammonia3. Figure 2: This image shows the virulence factors of H.pylori and how it can affect and survive in the human host. 5. How does H.pylori interact and damage the intestinal mucosa? Vac A exotoxin causes injury to the mucosal membrane3. Type IV secretion system that uses a pillus to inject effectors3. cagA causes actin remodeling and inhibits apoptosis3. Inhibits immune response by inhibiting T cell activation and proliferation3. Figure 3: This image shows the various ways in which Vac A interacts with epithelial cells and the various different ways it causes disruption 6. Sequelae Figure 4: Proportions of individuals with differing disease severity Association between H.pylori infection and gastric cancer8. Infection causes H pylori associated gastritis8. Increasing degenerative changes and evolution towards atrophy8. Nine fold risk of developing precancerous gastric conditions when H.pylori positive patients were compared with those without infection8. Strong association with poor socioeconomic conditions8. 7. Why does H pylori cause cancer This is not well understood, some ideas are: Chronic inflammatory response to infection pushes cells in the stomach lining towards oncogenesis 11. Damage of the mucosal membrane due to inflammation increases the carcinogenic effect of risk factors such as high salt intake and smoking12. Recent research suggests CagA may lead to inactivation tumor suppressor proteins like p5311. This protein normally leads cells into apoptosis. 8. Figure 5: The clinical outcomes of H.pylori 9. Signs & Symptoms Indigestion: this can be caused by an H pylori induced ulcer1. Can be accompanied by: Dull and burning pain worse on empty stomach, relieved briefly by antacids, lasts for minutes to hours and comes and goes over days and weeks5. Weight loss, vomiting, trouble in swallowing: can be caused by H.pylori induced cancer1. Figure 6: How helicobacter Pylori develops into an Gastric Ulcer 10. Diagnosis Blood test: antibody test meaning that it is difficult to tell whether the infection is past or current5. Breath test: 14C labeled urea drink, detection of the isotope in exhaled CO2 will indicate presence of urease secreted by H pylori 5 Biopsy taken during an endoscopy, tissue sample examined in the lab for presence of H.pylori5. X ray examination after barium meal (white chalky liquid allowing soft tissues to become visible on x-ray)5. Figure 7: Carbon-14 Breath Test 11. Genome interactions H. pylori has infected humans since they originated in the African continent6,7 The bacterium has evolved with us accumulating DNA changes as we migrated across the world6,7. Where old world met new e.g. as in South America, when European colonists arrived this co-evolution was disrupted6,7 Thus some individuals became infected with H. pylori variants with differently evolved ancestry6,7. This mismatch means that a harmless infection can become cancer causing6,7 The genomic sequence of the hosts compared to that of the microbes can predict of the risk of disease much better than when analysed alone6,7. It was shown that people from Tumaco Colombia find the majority of their DNA ancestry and most of their H. pylori strains come from Africa6,7 The mountain population from Tuquerres is 67% American/Indian and 31% European. Their H. pylori are mostly from European which replaced the native strains6,7. If the H. pylori strains have a different origin to their hosts, they are more likely to cause cancer6,7. Strains originating in Africa are mostly harmless Africans, but caused cancer in people with a largely American/Indian background6,7. 12. Treatment Double-dose PPI (e.g. 20 mg omeprazole) 10. decreases the stomach's production of acid allowing damaged tissue to heal. Examples of proton pump inhibitors include Lansoprazole, Omeprazole, Pantoprazole and more. Plus two antibiotics; this increases treatment success and antibiotic resistance9. Omeprazole 20mg, metronidazole 400 mg & clarithromycin 250 mg TDS Or, Omeprazole 20mg, amoxicillin 1 g and clarithromycin 500mg TDS 13. References 1. Information about Helicobacter Pylori. (2014). 1st ed. [ebook] London: Core the digestive disorders foundation, pp.2-5. Available at: http://www.nhs.uk/ipgmedia/national/core%20charity/assets/heli cobacterpylori.pdf 2. Blaser, M. J. (2006). "Who are we? Indigenous microbes and the ecology of human diseases". EMBO Reports 7 (10): 95660. 3. Wikimedia, (2014). Helicobacter Pylori Virulence Factors. [image] Available at: http://upload.wikimedia.org/wikipedia/commons/9/9a/H_pylori_ virulence_factors_en.png 4. H.pylori & Peptic Ulcers. (2014). 1st ed. [ebook] Bethesda: Clearinghouse, pp.1-6. Available at: http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/hpylori_50 8.pdf 5. Yong, E/ (2014). Human-microbe mismatch boosts risk of stomach cancer. [online] Available at: http://www.nature.com/news/human-microbe-mismatch- boosts-risk-of-stomach-cancer-1.14501 [Accessed 18 May.2014]. 6. Kodaman, N., Pazos, A., Schneider, B., Piazuelo, M., Mera, R., Sobota, R., Sicinschi, L., Shaffer, C., Romero-Gallo, J., de Sablet, T. and others, (2014). Human and Helicobacter pylori coevolution shapes the risk of gastric disease. Proceedings of the 8. Forman, D. (1998). Helicobacter Pylori: the gastric cancer problem. Gut, 43 (Suppl 1), p.33. 9. Uptodate.com, (2014). Helicobacter pylori infection and treatment. [online[ Avaliable at: .http://www.uptodate.com/contents/helicobacter- pylori-infection-and-treatment-beyond-the-basics 10. Patient.co.uk, (2014). Helicobacter Pylori [online] Available at: http://www.patient.co.uk/doctor/helicobacter-pylori-pro 11. National Cancer Institute, (2014). Helicobacter pylori and cancer. [online] Avaliable at: http://www.cancer.gov/cancertopics/factsheet/Risk/h-pylori-cancer 12. J, B. and P,M. (2014). Helicobacter pylori and Gastric Cancer. Digestive Disease, [online] 32(3). Available at: http://ncbi.nlm.nih.gov/pubmed/24732191 [Accessed 18 May. 2014]. 14. Image References 1. Helico.com. Epidemiology | The Helicobacter Foundation [Internet]. 2014 [23 April 2014]. Available from: http://www.helico.com/?q=Epidemiology 2. Upload.wikimedia.org. [Internet]. 2014 [23 April 2014]. Available from: http://upload.wikimedia.org/wikipedia/commons/9/9a/H_pylori_virulence_factors_en.png 3. Cover T, Blanke S. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nature Reviews Microbiology. 2005;3(4):320--332. 4. Helico.com. Epidemiology | The Helicobacter Foundation [Internet]. 2014 [23 April 2014]. Available from: http://www.helico.com/?q=Epidemiology 5. Kim E, Hong K, Hong H, Hahm K. Detouring the undesired route of Helicobacter pylori- induced gastric carcinogenesis. Cancers. 2011;3(3):3018--3028. 6. HealthTap. what is the effests of xycam 20mg on a developing peptic ulcer? [Internet]. 2014 [23 April 2014]. Available from: https://www.healthtap.com/user_questions/326787- what-is-the-effests-of-xycam-20mg-on-a-developing-peptic-ulcer 7. Static.groupon.hk, (2014). [online] Avaliable at: https://static.groupon.hk/56/20/1328191622056.jpg [Accessed 18th May.2014]