Clinical Characteristics and Helicobacter pylori Status of Gastric Cancer in Thailand

Background: Gastric cancer is the second leading course of cancer death worldwide and H. pylori infection is an important risk factor for gastric cancer development. This study was design to evaluate the clinical, pathological features, survival rate and prevalence of H. pylori infection in gastric cancer in Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings and H. pylori status were collected from gastric cancer patients from Thammasat university hospital during June 1996-December 2011. H. pylori infection was assessed by histological evaluation, rapid urease test and serological test. Clinical information, endoscopic findings and histopathology of all patients were recorded and compared between patients with active or non-active H. pylori infection. Results: A total of 100 gastric cancer patients (55 men and 45 women with mean age of 55±16.8 years) were enrolled in this study. Common presenting symptoms were dyspepsia (74%), weight loss (66%), anemia (63%) and anorexia (38%). Mean duration of symptoms prior to diagnosis was 98 days. Overall prevalence of H. pylori infection was 83% and active H. pylori infection was 40%. 1-year and 5-year survival rates were 43% and 0%. There was no significant difference between active H. pylori infection in different locations (proximal vs non-proximal: 47.1% vs 48.5%; P-value = 0.9, OR=0.9; 95%CI =0.3-3.1) and histology of gastric cancer (diffuse type vs intestinal type: 47.4% vs 50%; P-value= 0.8, OR=0.9, 95%CI=0.3-2.7). However, linitis plastica was significantly more common in non-active than active H. pylori infection (27.9% vs 0%; P-value <0.0001, OR =13.3, 95%CI=3.2-64.5). Moreover, gastric cancer stage 4 was higher in non-active than active H. pylori infection (93% vs 50%, P-value<0.001). Conclusions: Prevalence of H. pylori infection in Thai gastric cancer patients was high but active infection was low. Most gastric cancer patients presented in advance stage and had a grave prognosis. Screening for gastric cancer in high risk individuals might be an appropriate tool for early detection and improve the treatment outcome for this particular disease in Thailand.


Clinical Characteristics and Helicobacter pylori Status of Gastric Cancer in Thailand
Ratha-korn Vilaichone 1 *, Wirat Panarat 1 , Surasak Aekpongpaisit 2 , Voracha Mahachai 3 cancer. Due to the high incidence of gastric cancer, Japan developed the effective gastric cancer screening and H. pylori eradication program for prevention and early detection of this cancer (Asaka et al., 2014;Lin et al., 2014;Sano et al., 2014). In Thailand, gastric cancer is the sixth most common cancer in males and ninth in females. The annual incidence is 5 cases per 100,000 populations and had poor prognosis (Mahachai et al., 2011). Previous studies have suggested risk factors of gastric cancer included H. pylori infection, smoking, eating salty foods or fermented foods, family history of gastric cancer, gastric polyp and ethnic Japan, Chinese and Korean (Nomura et al., 1991;Parsonnet et al., 1991;Talley et al., 1991;Mahachai et al., 2011).
The pathogenesis of H. pylori in the development of gastric cancer has been suggested primarily from both epidemiological and basic research studies (Parsonnet et al., 1991, Uemura et al., 2001, Demirel et al., 2013, Karami et al., 2013, Basiri et al., 2014. The World Health Organization and International Agency for Research on Cancer consensus group stated in 1994 based on epidemiologic and histological evidence has classified H. pylori as a definite class I carcinogen (IARC 1994;Abeba et al., 2014). Prevalence of H. pylori infection in gastric cancer varies from 19% to 94% according to study from Spain (Martin-de Argila et al., 1997). In one meta-analysis, H. pylori seropositivity was 82.4% for patients with gastric cancer (Haung et al., 1998).
In Thailand, there are few studies on this area and the prevalence of H. pylori in gastric cancer may be underestimated. We conducted this study to evaluate the prevalence of active H. pylori infection and to compare the clinical spectrum and histology between active and non-active H. pylori infection of gastric cancer patients in our country.

Materials and Methods
All patients who have been detected as gastric cancer by histological evaluation in Thammasat university hospital between June 1996-December 2011 were included in this study. Active H. pylori infection was defined as positive from rapid urease test or histology. Non-active H. pylori infection was diagnosed if positive only from H. pylori serologic test (Anti-Helicobacter pylori ELISA IgG). Clinical information, endoscopic findings and histopathology of gastric cancer patients were recorded and compared between patients with active and non-active H. pylori infection. The gastric cancer was classified histologically according to the Lauren system into intestinal type and diffuses type by a single pathologist. Endoscopic features of gastric cancer were described as fungating mass, ulcerative mass or linitis plastica. The location of tumor was recorded as proximal (cardia/fundus) and non-proximal area (body and antrum). Staging of gastric carcinoma was classified according to TMN system.

Statistical analysis
The statistical analysis was performed by using descriptive statistics calculated the patient characteristics. The clinical findings of the patients were compared by independent-test or Chi-square test or Fisher's exact test where appropriate. The P-value <0.05 was considered to be statistically significant. All statistic analyses were performed using SPSS for Windows Version 19.0 (IBM Corp., Armonk, NY). The study was conducted according to the good clinical practice guideline, and was approved by our local ethics committee.

Results
A total of 100 patients with gastric cancer were included in the study. The mean age of the patients was 55 ±16.8 years (range 23-86 years). There were 55 men and 45 women with a male to female ratio of 1.2:1. Common presenting symptoms were dyspepsia (74%), weight loss (66%), anemia (63%) and anorexia (38%). The mean duration of symptoms prior to diagnosis was 98 days.

Discussion
Gastric cancer is one of the common cancer especially in the Asian countries. Since Warren and Marshall first isolated H. pylori and found its association with gastritis   DOI:http://dx.doi.org/10.7314/APJCP.2014.15.20.9005 Clinical Characterisitics andH pylori Status of Gastric Cancer in Thailand (Warren et al., 1983), many studies have suggested the relationship between H. pylori infection and gastric cancer (Parsonnet et al., 1991, Uemura et al., 2001, Demirel et al., 2013, Karami et al., 2013. In this study, the prevalence of active and non-active H. pylori infection in gastric cancer was 40% and 43% respectively. We demonstrated that active and non-active H. pylori infection were similar in the mean age, sex, gastric location and histological features of this tumor. However, linitis plastica and advanced gastric cancers (stage 4) were significantly more common in non-active than active H. pylori infection. The previous studies suggested that very advanced atrophic gastritis or in gastric cancer were unhealthy environment for H. pylori and might be not suitable for bacterial survival. Finally, H. pylori in those lesions was frequently disappear (Hazell et al., 1987, Robey-Cafferty et al., 1989, Haung et al., 1998, Vilaichone et al., 2003. The prevalence of H. pylori infection was high among gastric cancer patients in many countries such as 91% in Singapore (Chau et al., 2002), 78% in Japan (Ono et al., 2012) and 100% in Iran (Karami et al., 2013). In this study, we demonstrated that overall H. pylori infection in gastric cancer was 83%. However, the prevalence of H. pylori in gastric cancer depended on examine test. If used only the rapid urease test or histology to detect H. pylori infection, prevalence of H. pylori infection in gastric cancer patients would be only 53%. On the other hand, if use the serologic test, prevalence of H. pylori could be up to 93% in same group of patients (Vilaichone et al., 2003). Serologic tests are widely used for the diagnosis of H. pylori infection because of simple and convenient. IgM and IgA antibody testing have not proven to be useful clinically, whereas anti-H. pylori IgG had more reliable track record. IgG anti-H. pylori antibodies generally can be expected to be present by 4 weeks after infection. However the major disadvantage of serologic test was insufficient efficacy to detect active or current H. pylori infection because antibody tests could be remain positive for years even after H. pylori eradication. For these reasons, serologic test have limited clinical use especially to confirm cure of this bacterial infection (Vilaichone et al., 2006).
H. pylori screening and treatment is recommended as gastric cancer risk reduction strategy in high risk countries such as Japan, China and Korea and is most effective if screening before developing of atrophic gastritis (Fock et al., 2008). However, H. pylori screening and treatment is not recommended for gastric cancer prevention in low risk countries such as Thailand due to low cost effectiveness. In our study, the mortality and survival rate of Thai gastric cancer patients was very poor. To enhance the chance of early gastric cancer detection for better treatment outcome in low risk countries, the authors suggested to perform screening in high risk individuals such as family members of gastric cancer (esp. 1st degree relationship), age more than 40 years especially with alarming symptoms, previously document precancerous lesions (eg. atrophic gastritis, intestinal metaplasia or dysplasia) and certain ethnic group (eg. Japanese, Korean or Chinese people).
In conclusion, the prevalence of H. pylori infection in Thai gastric cancer patients was high but active H. pylori infection was low due to unhealthy environment for H. pylori survival in cancer tissue. Most of gastric cancer patients in Thailand were presented in advance stage and had grave prognosis. Screening of gastric cancer in high risk individuals might be an appropriate tool to early detection and improve the treatment outcome of gastric cancer in Thailand.