Clinical Characteristics and Helicobacter pylori Status of Gastric Cancer in Thailand

Vilaichone, Ratha-Korn,Panarat, Wirat,Aekpongpaisit, Surasak,Mahachai, Voracha Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

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 $55{\pm}16.8years$) 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.

Seven-Day Bismuth-based Quadruple Therapy as an Initial Treatment for Helicobacter pylori Infection in a High Metronidazole Resistant Area

Vilaichone, Ratha-korn,Prapitpaiboon, Hatainuch,Gamnarai, Pornpen,Namtanee, Juraiwan,Wongcha-um, Arti,Chaithongrat, Supakarn,Mahachai, Varocha Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.

Virulence Genes of Helicobacter pylori in Gastritis, Peptic Ulcer and Gastric Cancer in Laos

Vannarath, Sengdao,Vilaichone, Ratha-Korn,Rasachak, Bouachanh,Mairiang, Pisaln,Yamaoka, Yoshio,Shiota, Seiji,Binh, Tran Thanh,Mahachai, Varocha Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: Helicobacter pylori (H. pylori) infection is an established cause of peptic ulcers and gastric cancer. The aim of this study was to identify H. pylori genotypes and to examine their associations with geographical regions and gastritis, peptic ulcers and gastric cancer in Laos. Materials and Methods: A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010 - March 2012 were enrolled. Two biopsy specimens (one each from the antrum and corpus) were obtained for CLO testing and only CLO test-positive gastric tissue were used to extract DNA. PCR and sequencing were identified for variants of the cagA and vacA genotypes. Results: Some 119 Laos patients (36.2%) were found to be infected with H. pylori including 83 with gastritis, 13 with gastric ulcers (GU), 20 with duodenal ulcers (DU) and 3 with gastric cancer. cagA was detected in 99.2%. East-Asian-type cagA (62%) and vacA s1c (64.7%) were predominant genotypes in Laos. vacA s1c-m1b was significantly higher in GU than gastritis (53.8% vs. 24.1%; P-value=0.04) whereas vacA s1a-m2 was significantly higher in DU than gastritis (40.0% vs. 16.9%; P-value=0.03). East-Asian-type cagA and vacA s1c were significantly higher in highland than lowland Lao (100% vs. 55.8%; P-value=0.001 and 88.2% vs. 61.5%, P-value=0.03 respectively). Conclusions: H. pylori is a common infection in Laos, as in other countries in Southeast Asia. The cagA gene was demonstrated in nearly all Laos patients, cagA and vacA genotypes being possible important factors in explaining H. pylori infection and disease outcomes in Laos.

Effects of the CYP2C19 Genetic Polymorphism on Gastritis, Peptic Ulcer Disease, Peptic Ulcer Bleeding and Gastric Cancer

Jainan, Wannapa,Vilaichone, Ratha-Korn Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: The CYP2C19 genotype has been found to be an important factor for peptic ulcer healing and H. pylori eradication, influencing the efficacy of proton pump inhibitors (PPIs) and the pathogenesis of gastric cancer. The aim of this study was to investigate clinical correlations of the CYP2C19 genotype in patients with gastritis, peptic ulcer disease (PUD), peptic ulcer bleeding (PUB) and gastric cancer in Thailand. Materials and Methods: Clinical information, endoscopic findings and H. pylori infection status of patients were assessed between May 2012 and November 2014 in Thammasat University Hospital, Thailand. Upper GI endoscopy was performed for all patients. Five milliliters of blood were collected for H. pylori serological diagnosis and CYP2C19 study. CYP2C19 genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) and classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: A total of 202 patients were enrolled including 114 with gastritis, 36 with PUD, 50 with PUB and 2 with gastric cancer. Prevalence of CYP2C19 genotype was 82/202 (40.6%) in RM, 99/202 (49%) in IM and 21/202 (10.4%) in PM. Overall H. pylori infection was 138/202 patients (68.3%). H. pylori infection was demonstrated in 72% in RM genotype, 69.7% in IM genotype and 47.6% in PM genotype. Both gastric cancer patients had the IM genotype. In PUB patients, the prevalence of genotype RM (56%) was highest followed by IM (32%) and PM(12%). Furthermore, the prevalence of genotype RM in PUB was significantly greater than gastritis patients (56% vs 36%: p=0.016; OR=2.3, 95%CI=1.1-4.7). Conclusions: CYP2C19 genotype IM was the most common genotype whereas genotype RM was the most common in PUB patients. All gastric cancer patients had genotype IM. The CYP2C19 genotype RM might be play role in development of PUD and PUB. Further study in different population is necessary to verify clinical usefulness of CYP2C19 genotyping in development of these upper GI diseases.

Colorectal Cancer in the Central Region of Thailand

Phiphatpatthamaamphan, Kittichet,Vilaichone, Ratha-Korn Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

Background: Colorectal cancer is one of the major health problems worldwide. However, limited studies have been reported from ASEAN countries. This study was conducted to evaluate clinical characteristics and survival of colorectal cancer cases aged <65 years and ${\geq}65$ years in the central region of Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings and treatment outcome were collected and reviewed from Thammasat University Hospital, Pathumthani, Thailand between November 2011 and October 2015. Results: A total of 121 colorectal cancer patients, comprising 69 men and 52 women with a mean age of 65.8 years, were included. There were 57 aged <65 years and 64 aged ${\geq}65$ years. Common presenting symptoms were abdominal pain (37%), weight loss (34%) and anemia (32%). Mean duration of symptoms prior to diagnosis was 173 days. However, longer diagnosis time was demonstrated in patients aged <65 years than age more than ${\geq}65$ years (119.4 vs 58.4 days, P-value=0.30). Colonic fungating mass was the most common endoscopic finding (64.4%) and the location was significantly more commonly left than right side of the colon, both in younger and elderly groups (87.7% vs 12.3%, P=0.02 and 70.3% vs 29.7%, P=0.02, respectively). Adenocarcinoma with moderated differentiated was the most common histology (67.3%). More than half of the patients presented with advanced stage (28.9% with TNM stage 3 and 38.8% TNM stage 4, respectively). Overall 1-year and 5-year survival rates were 76.9% and 5%. Conclusions: Most colorectal cancer patients in Thailand have adenocarcinomas and present at advanced stage with poor prognosis. Screening of high risk patients and early detection might be essential factors to improve the treatment outcome and overall survival rate of colon cancer patients in Thailand and other ASEAN countries.

High Prevalence of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Thailand

Wanich, Nattawat,Vilaichone, Ratha-Korn,Chotivitayatarakorn, Peranart,Siramolpiwat, Sith Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: Chronic hepatitis B (CHB) infection is one of the important causes of hepatocellular carcinoma (HCC) in Thailand, involved in the pathogenesis and leading to a development of HCC with or without cirrhotic changes of the liver. This study was aimed to investigate the predictive factors for HCC among CHB patients in a tertiary care center in Thailand. Materials and Methods: We conducted a retrospective study of CHB patients with or without HCC during the period of January 2009 and December 2014 at Thammasat University Hospital, Pathumthani, Thailand. Data on clinical characteristics, biochemical tests and radiologic findings were collected from review of medical records. Results: A total of 266 patients were diagnosed with CHB in Thammasat university hospital during the study period. However, clinical information of only 164/266 CHB patients (98 males, 66 females with mean age of 49.4 years) could be completely retrieved in this study. The prevalence of HCC in CHB infection in this study was 38/164 (23.2%). CHB patients with HCC had a mean age older than those without HCC (59.5 vs 47 years, P-value = 0.01). Furthermore, history of upper GI bleeding, tattooing, blood transfusion, and chronic alcoholism were significantly more common in CHB patients with HCC than patients without HCC (13.2% vs 3.2% P-value 0.03, OR = 4.6, 95%CI = 1.2-18.1, 20% vs 3.9%, P-value = 0.01, OR= 6.1, 95% CI= 1.6-23.6, 20% vs 6.3%, P-value = 0.03, OR = 3.8, 95%CI =1.1-12.7, 62.2% vs 30.3%, P-value <0.0001, OR = 3.7, 95%CI= 1.7-8.1 respectively). Interestingly, more CHB patients with HCC had evidence of cirrhosis than those without HCC (78.9% vs 20.4%, P-value <0.0001, OR = 14.6, 95%CI = 5.8-36.7). In CHB patients with HCC, surgical therapy provided longer survival than radiofrequency ablation (RFA) (72 vs 46.5 months, P-value= 0.04). The mean survival time after HCC diagnosis was 17.2 months. Conclusions: HCC remains a major problem among patients with CHB infection in Thailand. Possible risk factors are male gender, history of upper GI bleeding, chronic alcoholism, tattooing, blood transfusion and evidence of cirrhosis. For early stage HCC patients, surgical treatment provided longer survival time than RFA. Most HCC patients presented with advanced disease and had a grave prognosis. Appropriate screening of CHB patients at risk for HCC might be an appropriate approach for early detection and improvement of long-term outcomes.

Effect of IL-1 Polymorphisms, CYP2C19 Genotype and Antibiotic Resistance on Helicobacter pylori Eradication Comparing Between 10-day Sequential Therapy and 14-day Standard Triple Therapy with Four-Times-Daily-Dosing of Amoxicillin in Thailand: a Prospect

Phiphatpatthamaamphan, Kittichet,Vilaichone, Ratha-korn,Siramolpiwat, Sith,Tangaroonsanti, Anupong,Chonprasertsuk, Soonthorn,Bhanthumkomol, Patommatat,Pornthisarn, Bubpha,Mahachai, Varocha Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. Materials and Methods: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Conclusions: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

Thailand Consensus on Helicobacter pylori Treatment 2015

Mahachai, Varocha,Vilaichone, Ratha-Korn,Pittayanon, Rapat,Rojborwonwitaya, Jarin,Leelakusolvong, Somchai,Kositchaiwat, Chomsri,Mairiang, Pisaln,Praisontarangkul, Ong-Ard,Ovartlarnporn, Buncha,Sottisu Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes.

Antibiotic Resistant Pattern of Helicobacter Pylori Infection Based on Molecular Tests in Laos

Vannarath, Sengdao,Vilaichone, Ratha-korn,Rasachak, Bouachanh,Mairiang, Pisaln,Yamaoka, Yoshio,Mahachai, Varocha Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1

Background: The efficacy of standard treatment of Helicobacter pylori (H. pylori) is declining because of antibiotic resistance. Clarithromycin resistance is also increasing in many Asian countries. The aim of this study was to determine the antibiotic susceptibility patterns of H. pylori infection and clinical association in Laos. Materials and Methods: A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010-March 2012 were enrolled in this study. During gastroscopy, 4 biopsies were collected (2 each from the antrum and body) for CLO-test and histopathology. Only the positive CLO-test gastric tissues was stored at $-80^{\circ}C$ in a freezer until DNA was extracted and a GenoType$^{(R)}$HelicoDR test was conducted for detecting mutations in the rrl gene encoding 23S rRNA (clarithromycin resistance) and mutations in gyrA gene (fluoroquinolone resistance). Results: Of the total, 119 Lao patients (36.2%) were infected with H. pylori including 59 males (49.6%) and 60 females (50.4%) with a mean age of 46 years. Clarithromycin and fluoroquinolone resistance of H. pylori infection was demonstrated in 15 (12.6%) and 16 strains (13.4%) respectively. In clarithromycin resistance, the number of patients who had education above primary school and $BMI{\geq}25kg/m^2$ were significantly higher than those who had education below primary school and BMI<$25kg/m^2$ (23.1% vs 7.5%, P-value= 0.036 and 20.5% vs 8%, P-value= 0.048, respectively). In fluoroquinolone resistance, the number of lowland Lao was significantly higher than those of non-lowland (highland and midland) Lao ethnic groups (16.7% vs 0%, P-value= 0.039). Conclusions: H. pylori infections remain common in Laos. Clarithromycin and fluoroquinolone resistance with H. pylori infection are growing problems. Education above primary school and $BMI{\geq}25kg/m^2$ might be predictors for clarithromycin resistance and lowland Lao ethnicity might be predictors for fluoroquinolone resistance with H. pylori infection in Laos.

Late Stage and Grave Prognosis of Esophageal Cancer in Thailand

Nun-anan, Pongjarat,Vilaichone, Ratha-korn Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: Esophageal cancer is one of the major health concerns in Southeast Asian countries, including Thailand. However, only a limited number of studies have been reported from this region. This study was designed to evaluate the prevalence, clinical characteristics and survival rate of esophageal cancer in Thailand. Materials and Methods: Clinical information, histological features and endoscopic findings were collected from a tertiary care center in central region of Thailand between September 2011- November 2014 and reviewed. Results: A total of 64 esophageal cancer patients including 58 men and 6 women with mean age of 62.6 years were enrolled. Common presenting symptoms were dysphagia (74%), dyspepsia (10%) and hematemesis (8%). Mean duration of symptoms prior to diagnosis was 72 days. Esophageal stenosis with contact bleeding was the most common endoscopic finding (55.6%). The location of cancer was found in proximal (16%), middle (50%) and distal (34%) esophagus. Squamous cell carcinoma was far more common histology than adenocarcinoma (84.2% vs 10.5%). However, esophageal adenocarcinoma was significantly more common than squamous cell carcinoma in distal area of esophagus (100% vs 22.9%; p=0.0001, OR=1.6, 95%CI=1.1-2.2). Esophageal cancer stages 3 and 4 accounted for 35.2% and 59.3% respectively. Overall 2-year survival rate was 20% and only 16% in metastatic patients. Conclusions: Most esophageal cancer patients in Thailand have squamous cell carcinoma and nearly all present at advanced stage with a grave prognosis. Screening of high risk individuals and early detection might be important keys to improve the survival rate and treatment outcome in Thailand.