From Helicobacter Pylori to Peptic Ulcer to Gastric Cancer

Peptic ulcer is the most common chronic illness of the digestive system causing on-and-off symptoms of upper abdominal pain, fullness, gas and bloating. In some patients, it may also give rise to serious complications such as bleeding, bowel perforation, and obstruction. Ulcer bleeding (fig.1) is one of the most common reasons for emergency hospital admission and the incidence of this condition in Hong Kong tops the list in the whole world.

Fig. 1 Peptic ulcer seen under endoscopy

Acid - the Culprit of Peptic Ulcers?

A German physician so stated a century ago: 'No acid, no ulcer.' The treatment of peptic ulcers has for a long time been concentrated on suppressing acid secretion in the stomach by long-term medication or surgery. Potent and expensive ulcer healing drugs have been developed which merely suppress acid secretion without changing the natural history of the disease. Once medication is discontinued, ulcers invariably recur within a few months.

Helicobacter Pylori (HP) Closely Associated with the Disease

In 1983, researchers in Australia discovered a bacterium residing in the stomach of patients with chronic gastritis (inflammation of the stomach). Further studies showed that this bacterium, subsequently called Helicobacter pylori (fig. 2), was found in at least 90 per cent of patients suffering from peptic ulcers. The bacteria protect themselves from the high acidity in the stomach by producing 'urease' in the gastric mucosa, which is an enzyme that metabolizes urea and neutralizes gastric acid. They also elaborate various toxic substances which induce inflammation and cause cell damage in the stomach and the duodenum.

Fig.2 Helicobacter pylori seen under an electronic microscope

HP Infection Treatment vs Acid Suppression Treatment

In view of these findings, Prof. Joseph Sung of the Department of Medicine and Therapeutics, together with Prof. Sydney Chung of the Department of Surgery and Prof. Augustine Cheng of the Department of Microbiology, resolved to study the effects of treating HP infection on the healing and recurrence of peptic ulcers. Their research received a grant of HK$386,000 from the Research Grants Council in 1993.

The researchers first studied a group of 153 patients with duodenal ulcer, the more common type of peptic ulcers. These patients with HP infection and duodenal ulcers were randomized to receive either a one-week course of a three-drug regimen (bismuth, tetracycline and metronidazole) to treat HP infection, or four weeks of omeprazole (a potent acid suppression drug) in addition to the three-drug regimen. As a result, HP infection was cured in over 90 per cent of cases in both groups. There was, however, no significant difference in ulcer healing between the two groups despite the fact that one group of patients had not received any medication for acid suppression.

In a second study, 50 patients with gastric ulcer on a one-week course of the three-drug regimen was compared to 50 patients on four weeks of omeprazole only. Once again, results showed that ulcer healing in those given treatment for HP infection alone was by no means inferior to those given the more expensive acid-suppressing drug. In fact, within a one-year follow-up period, ulcer recurrence was documented in 50 per cent of the group who received only omeprazole as compared with two per cent (one patient) among those who received the three-drug therapy.

These two studies indicate a causal relationship between peptic ulcers and HP infection. They demonstrate that the treatment of HP infection alone is sufficient for the healing of peptic ulcers, and that the long-term use of acid suppressing drugs is not necessary. Peptic ulcers can be treated as an infectious disease just like pneumonia. This new therapy provides a permanent cure for the chronic digestive disease at a remarkably low cost.

HP Reinfection

In a follow-up study conducted 12 months afterwards, patients cured of HP infection were retested for the bacterium. HP infection had reappeared in the stomach of about 10 per cent of the subjects. This may be due either to incomplete eradication of the bacterium by the one-week therapy or to reinfection. The research group then proceeded to study the possible routes of reinfection. One possible channel of HP transmission is the use of chopsticks in eating.

Probing the Link between HP Infection and Gastric Cancer

The next goal of the research team is to study the possible relationship between HP infection and gastric cancer, the cancer with the highest mortality rate in China. Epidemiological studies based on serological tests showed a strong association between HP infection and gastric cancer. It is postulated that HP induces chronic inflammation of the stomach and gradual changes in the cell nature of the stomach, resulting in the development of the malignancy. It is unknown whether treating the infection can reverse the process of cancer development. In a collaborative study with Beijing Medical University, the research group has started mass screening and treatment for HP in Yantai county in Shangdong province, a high prevalence area for gastric cancer. It is hoped that the findings will help devise a treatment strategy to forestall the development of gastric cancer.

Prof. Joseph Sung graduated from the University of Hong Kong in 1983 and received training in internal medicine and gastroenterology at the Prince of Wales Hospital. He furthered his training at the University of Calgary in Canada where he obtained his Ph.D. in 1991. A year later, he joined The Chinese University as lecturer in medicine, becoming senior lecturer in 1994. He was promoted to reader rank in 1996 and became head of the Division of Gastroenterology and Hepatology in the Department of Medicine of the University as well as honorary consultant gastroenterologist at the United Christian Hospital.
Prof. Sung obtained his MRCP in 1986, his FRCPEd in 1995, and his FRCP as well as his MD (CUHK) in 1997. His research interests are Helicobacter pylori and peptic ulcer diseases.
Prof. Sydney Chung Sheung-chee received his medical education in Ireland and obtained his M.B. B.Ch. and BAO degrees from the National University of Ireland in 1980. After a year of internship in Scotland, Prof. Chung returned to Hong Kong to serve as medical officer in Kwong Wah Hospital.
In 1984 Prof. Chung joined The Chinese University as lecturer in the Department of Surgery. He was promoted to senior lecturer rank in 1988, reader in 1992, and was appointed professor of surgery in 1994. Prof. Chung was awarded an MD degree by the University in 1988. He is also a fellow of the Royal Colleges of Surgeons of Edinburgh and Glasgow, and a member of the Royal College of Physicians of the UK.
Prof. Augustine F.B. Cheng studied microbiology at the University of Manitoba, Canada, and received his B.Sc. in 1969, his M.Sc. in 1973, his Ph.D. in 1975, and MD in 1977.
From 1978 to 1983, he was a staff physician at the Federal Deer Lodge Hospital in Manitoba. He joined The Chinese University in 1983 as lecturer in microbiology, becoming senior lecturer in 1989, and reader in 1992.
Prof. Cheng is a fellow of the Royal College of Pathologists, the Hong Kong Academy of Medicine (pathology), and the Royal College of Pathologists of Australasia.
Prof. Cheng has published widely on his areas of research interest, which include antimicrobial susceptibility testing, pharmacokinetics, mechanisms of resistance and clinical trials, development of rapid diagnostic methods for infectious diseases, molecular epidemiology and control of hospital infection, and mycobacteriology and helicobacteriology.

References
  • Hosking, S.W., Ling, T.K.W., Chung, S.C.S., Yung, M.Y., Cheng, A.F.B., Sung, J.J.Y. & Li, A.K.C., 'Duodenal ulcer healing by eradication of H. pylori without anti-acid treatment: randomized controlled trial', Lancet, 1994, 343, pp. 508-510.
  • Sung, J.J.Y., Chung, S.C.S., Ling, T.K.W., Yung, M.Y., Leung, V.K.S., Ng, E.K.W., Li, M.K.K., Cheng, A.F.B. & Li, A.K.C., 'Antibacterial treatment of gastric ulcers associated with H. pylori', New England Journal of Medicine, 1995, 332, pp. 139-142.
  • Sung, J.J.Y., Chung, S.C.S., Ling, T.K.W., Yung, M.Y., Cheng, A.F.B., Hosking, S.W. & Li, A.K.C., 'One-year follow-up of duodenal ulcers after one-week triple therapy for H. pylori', American Journal of Gastroenterology, 1993, 89, pp. 199-202.
  • Leung, W.K., Sung, J.J.Y., Ling, T.K.W., Siu, K.L.K. & Cheng, A.F.B., 'Does the use of chopsticks for eating transmit H. pylori?', Lancet, 1997, 350, p. 31.