Treatment outcomes among high-risk neuroblastoma patients receiving non-immunotherapy regimen: Multicenter study on behalf of the Thai Pediatric Oncology Group.

BACKGROUND: Neuroblastoma is the most common extracranial malignant solid tumor during childhood. Despite intensified treatment, patients with high-risk neuroblastoma (HR-NBL) still carry a dismal prognosis. The Thai Pediatric Oncology Group (ThaiPOG) proposed the use of a multimodality treatment to improve outcomes of HR-NBL in non-immunotherapy settings. METHODS: Patients with HR-NBL undergoing ThaiPOG protocols (ThaiPOG-NB-13HR or -18HR) between 2013 and 2019 were retrospectively reviewed. Patient demographic data, treatment modalities, outcomes, and prognostic factors were evaluated and analyzed. RESULTS: A total of 183 patients with HR-NBL undergoing a topotecan containing induction regimen were enrolled in this study. During the consolidation phase (n = 169), 116 patients (68.6%) received conventional chemotherapy, while 53 patients (31.4%) underwent hematopoietic stem cell transplantation (HSCT). The 5-year overall survival (OS) and event-free survival (EFS) were 41.2% and 22.8%, respectively. Patients who underwent HSCT had more superior 5-year EFS (36%) than those who received chemotherapy (17.1%) (p = .041), although they both performed similarly in 5-year OS (48.7% vs. 39.8%, p = .17). The variation of survival outcomes was observed depending on the number of treatment modalities. HSCT combined with metaiodobenzylguanidine (MIBG) treatment and maintenance with 13-cis-retinoic acid (cis-RA) demonstrated a desirable 5-year OS and EFS of 65.6% and 58.3%, respectively. Poorly or undifferentiated tumor histology and cis-RA administration were independent factors associated with relapse and survival outcomes, respectively (p < .05). CONCLUSION: A combination of HSCT and cis-RA successfully improved the outcomes of patients with HR-NBL in immunotherapy inaccessible settings.

Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study.

BACKGROUND: Neuroblastoma is the most common extra-cranial solid tumor among children. Despite intensive treatment, patients with advanced disease mostly experience dismal outcomes. Here, we proposed the use of topotecan and cyclophosphamide containing induction regimen as an upfront therapy to high risk neuroblastoma patients. METHODS: Patients with high risk neuroblastoma undergoing ThaiPOG high risk neuroblastoma protocol from 2016 to 2017 were studied. All patients received 6 cycles of induction regimen consisting of 2 cycles topotecan (1.2 mg/m2/day) and cyclophosphamide (400 mg/m2/day) for 5 days followed by cisplatin (50 mg/m2/day) for 4 days combined with etoposide (200 mg/m2/day) for 3 days on the third and fifth cycles and cyclophosphamide (2100 mg/m2/day) for 2 days combined with doxorubicin (25 mg/m2/day) and vincristine (0.67 mg/m2/day) for 3 days on the fourth and sixth cycles. Treatment response after the 5th cycle before surgery and treatment-related toxicities after each topotecan containing induction cycle were evaluated. Relevant prognostic factors were analyzed to measure the treatment response among those patients. RESULTS: In all, 107 high risk neuroblastoma patients were enrolled in the study. After the 5th cycle of induction regimen, the patients achieved complete response (N = 2), very good partial response (N = 40), partial response (N = 46) and mixed response (N = 19). None of the patients experienced stable disease or disease progression. The most significant prognostic factor was type of healthcare system. The most common adverse effect was febrile neutropenia followed by mucositis, diarrhea and elevated renal function. CONCLUSION: The topotecan and cyclophosphamide containing induction regimen effectively provides favorable treatment response. The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.

Childhood cancer incidence and survival in Thailand: A comprehensive population-based registry analysis, 1990-2011.

BACKGROUND: Southeast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20-year period. METHODS: Cancer cases diagnosed in children ages 0-19 years (n = 3574) from 1990 to 2011 were extracted from five provincial population-based Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Age-standardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the Kaplan-Meier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC). RESULTS: The ASR of all childhood cancers during the study period was 98.5 per million person-years with 91.0 per million person-years in 1990-2000 and 106.2 per million person-years in 2001-2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P < 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5-year survival for all childhood cancers significantly improved from 39.4% in 1990-2000 to 47.2% in 2001-2011 (P < 0.01). CONCLUSIONS: Both childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in low- and middle-income countries can improve understanding of cancer etiology and pediatric health care disparities.

Opisthorchiasis with proinflammatory cytokines (IL-1ß and TNF-α) polymorphisms influence risk of intrahepatic cholangiocarcinoma in Thailand: a nested case-control study.

BACKGROUND: Chronic inflammation and repeated infection with Opisthorchis viverrini (O. viverrini) induces intrahepatic cholangiocarcinoma (ICC). Inflammatory cytokines such as interleukin (IL) and tumor necrosis factor (TNF) are substances in the immune system that promote inflammation and causes disease to progress. Genes that help express proinflammatory cytokines can affect an individual's susceptibility to disease, especially in cancer-related chronic inflammation. This study aimed to investigate risk factors for ICC with a focus on opisthorchiasis and polymorphisms of proinflammatory cytokines (IL-1ß and TNF-α). METHODS: This study was a nested case-control study within a cohort study. 219 subjects who developed a primary ICC were identified and matched with two non-cancer controls from the same cohort based on sex and age at recruitment (±3 years). An O. viverrini-IgG antibody was assessed using enzyme linked immunosorbent assay. IL-1ß and TNF-α polymorphisms were analyzed using a polymerase chain reaction with high resolution melting analysis. Associations between variables and ICC were assessed using conditional logistic regression. RESULTS: Subjects with a high infection intensity had higher risk of ICC than those who had a low level (OR = 2.1; 95% CI: 1.2-3.9). Subjects with all genotypes of TNF-α (GG, GA, AA) and high infection intensity were significantly related to an increased risk of ICC (p < 0.05). CONCLUSIONS: Polymorphisms of IL-1ß and TNF-α are not a risk of ICC, but an individual with O. viverrini infection has an effect on all genotypes of the TNF-α gene that might promote ICC. Primary prevention of ICC in high-risk areas is based on efforts to reduce O. viverrini infection.

Fetal Anemia Causing Hydrops Fetalis From an Alpha-Globin Variant: Homozygous Hemoglobin Constant Spring.

BACKGROUND: Fetal anemia is often assumed to be due to red cell alloimmunization and Parvovirus infection, and can lead to hydrops fetalis and death in utero. Other causes, such as mutations of hemoglobin alpha, are less commonly considered. METHODS: We report 7 cases with fetal anemia causing hydrops fetalis. Serial Doppler ultrasound for measurement peak systolic velocity (PSV) of middle cerebral artery (MCA) was used for evaluation of fetal anemia. Fetal anemia is suggested if the MCA/PSV ratio is >1.5 multiple of median. Cordocentesis was performed subsequently to find the cause of fetal anemia and check fetal hemoglobin for consideration of intrauterine infusion. Investigations for fetal anemia include complete blood count, blood morphology, and blood group of mother and fetus, reticulocyte counts, red cell indices, screening for thalassemia, hemoglobin typing, acid elution test, parvovirus B 19 serology, and TORCH titer (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, and syphilis). Intrauterine infusion, using irradiated prestorage filtered red cell with hematocrit level of 80%, is indicated if fetal hemoglobin is <10 g/dL. RESULT: Seven cases with fetal anemia were prenatally diagnosed from gestational ages 20 to 34 weeks. Initial hematocrit in these cases varied from 9% to 17.2%. In each case, causes of anemia were determined using the investigations listed above. All cases underwent uneventfully up to 3 intrauterine transfusions. DNA study for thalassemia demonstrated homozygous Constant Spring (CS) in 5 cases, homozygous CS with heterozygous E in 1 case, and compound heterozygous CS and Pakse in 1 case. The perinatal outcomes were normal term in 5 cases, preterm in 2 cases. Low birth weight was determined in 2 cases. The screening for thalassemia major, including the osmotic fragility and dichlorophenol indophenol precipitation test (DCIP), is not helpful for detecting hemoglobin variants such as Constant Spring or Pakse. SUMMARY: This study emphasizes homozygous Constant Spring and compound heterozygous CS and Pakse as a cause of hydrops fetalis. Proper management for the fetus after diagnosis can lead to a good fetal outcome. Prevention control programs should include screening of parents for the heterozygous state.

Breast Cancer Incidence Trends and Projections in Northeastern Thailand.

BACKGROUND: The northeast has the lowest incidence of breast cancer of all regions in Thailand, although national rates are increasing. The heterogeneity in subnational trends necessitates a comprehensive evaluation of breast cancer incidence trends and projections to provide evidence for future region-specific strategies that may be employed to attenuate this growing burden. METHODS: Joinpoint regression and age-period-cohort modeling were used to describe trends from 1988-2012. Data was projected from three separate models to provide a range of estimates of incidence to the year 2030 by age group. RESULTS: Age-standardized rates (ASRs) increased significantly for all women from 1995-2012 by 4.5% per year. Rates for women below age 50 increased by 5.1% per year, while women age 50 years and older increased by 6% per year from 1988-2012. Projected rates show that women age 50 years and older have the largest projected increase in ASRs by 2030 compared to younger women and all women combined. CONCLUSIONS: Breast cancer trends in Khon Kaen are presently lower than other regions but are expected to increase and become comparable to other regions by 2030, particularly for women ages 50 years and older.

The XRCC 1 DNA repair gene modifies the environmental risk of stomach cancer: a hospital-based matched case-control study.

BACKGROUND: Previous studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population. METHODS: Hospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression. RESULTS: The Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30-10.72) compared with Gln/Gln homozygosity. The effect of the XRCC1gene on the risk of stomach cancer was modified by both a high intake of vegetable oils and salt (p = 0.036 and p = 0.014), particularly for the Arg/Arg homozygous genotype. There were, however, no additive effects on the risk of stomach cancer between variants of the XRCC1gene and smoking,alcohol or pork oil consumption. CONCLUSIONS: The effect of the XRCC1 gene homozygosity, particularly Arg/Arg, on the risk for stomach cancer was elevated by a high intake of vegetable oils and salt.

Lupus Anticoagulant-hypoprothrombinemia Syndrome (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases.

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.

Differences in childhood leukemia incidence and survival between Southern Thailand and the United States: a population-based analysis.

BACKGROUND: Childhood leukemia incidence and survival varies globally, and this variation may be attributed to environmental risk factors, genetics, and/or disparities in diagnosis and treatment. PROCEDURE: We analyzed childhood leukemia incidence and survival trends in children aged 0-19 years from 1990 to 2011 in Songkhla, Thailand (n = 316) and compared these results to US data from the Surveillance, Epidemiology, and End Results (SEER) registry (n = 6,738). We computed relative survival using Ederer II and estimated survival functions using the Kaplan-Meier method. Changes in incidence and 5-year survival by year of diagnosis were evaluated using joinpoint regression and are reported as annual percent changes (APC). RESULTS: The age-standardized incidence of leukemia was 3.2 and 4.1 cases per 100,000 in Songkhla and SEER-9, respectively. In Songkhla, incidence from 1990 to 2011 significantly increased for leukemia (APC = 1.7%, P = 0.031) and acute lymphoblastic leukemia (ALL) (APC = 1.8%, P = 0.033). Acute myeloid leukemia (AML) incidence significantly increased (APC = 4.2%, P = 0.044) and was significantly different from the US (P = 0.026), where incidence was stable during the same period (APC = 0.3%, P = 0.541). The overall 5-year relative survival for leukemia was lower than that reported in the US (43 vs. 79%). Five-year survival significantly improved by at least 2% per year from 1990 to 2011 in Songkhla for leukemia, ALL, and AML (P < 0.050). CONCLUSIONS: While leukemia and ALL incidence increased in Songkhla, differences in leukemia trends, particularly AML incidence, may suggest etiologic or diagnostic differences between Songkhla and the US. This work highlights the importance of evaluating childhood cancer trends in low- and middle-income countries.

Hormonal contraceptive use and breast cancer in Thai women.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women. METHODS: A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. RESULTS: The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant (95% CI, 0.65-2.65). No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives (oral contraception: HR = 1.35, 95% CI, 0.65-2.78; injection contraception: HR = 1.25, 95% CI, 0.56-2.80), and there was no relationship between duration of hormonal contraceptive use and breast cancer. CONCLUSIONS: There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.

Childhood neoplasms: analysis of Thai children 2010.

BACKGROUND: Between 1990 and 2010, many national and international factors converged to both beneficially and antagonistically affect people's health as well as the Thai healthcare system. Among these were: a falling birth rate in Thailand and a gradual decline in poverty-related diseases. Cancer becomes the most common cause of death. OBJECTIVE: To analyze Thailand's childhood neoplasm issues for baseline information for changing medical education, services and research. MATERIAL AND METHOD: Information on the illnesses of in-patients, out-patients and casualties was based on hospital withdrawals nationwide from the three health insurance schemes in the fiscal year 2010. The data, which included 96% of the population, were analyzed by age groups and burden of neoplasm disease. RESULTS: The children with neoplasms were treated 127,597 times at outpatient departments (OPD) and 19,159 times at inpatient departments (IPD) at community hospitals (4.3%), provincial hospitals (8.50%), regional or university hospitals (86.1%) and private hospitals (1.1%). Malignant neoplasms of lymphoid hematopoietic and related tissues were the most common in both IPD and OPD settings, which resulted in the highest cost of treatment. Tumors of the central nervous system were associated with the highest cost. The mean length of stay for all patients with neoplasm was 7.85 days. CONCLUSION: Sufficient budget should be allocated to the more heavily frequented treatment center Specific and better care, national treatment protocols for each type of childhood cancer (including palliative care) should be developed to improve the treatment outcomes and/or the quality of life. Medical schools and health service systems need to be recalibrated to respond proactively to these changes being experienced by the healthcare system.

Treatment outcomes of high-dose chemotherapy plus stem cell rescue in high-risk neuroblastoma patients in Thailand.

BACKGROUND: In 2013, the Thai Pediatric Oncology Group (ThaiPOG) introduced a national protocol in which high-dose chemotherapy plus stem cell rescue is performed without immunotherapy. METHODS: This study aimed to elucidate the outcomes of high-risk neuroblastoma (HR-NB) patients treated with the ThaiPOG protocol. This retrospective cohort review included 48 patients (30 males, 18 females) with a median age of 3 years (range, 8 months to 18 years) who were treated at 5 ThaiPOG treatment centers in Thailand in 2000-2018. RESULTS: Eight of the 48 patients showed MYCN amplification. Twenty-three patients (48%) received 131I-meta-iodobenzylguanidine prior to high-dose chemotherapy and stem cell rescue. The majority of patients achieved a complete or very good response prior to consolidation treatment. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.1% and 40.4%, respectively. Patients aged >2 years had a nonsignificantly higher mortality risk (hazard ratio [HR], 2.66; 95% confidence interval [CI], 0.92-7.68; P=0.07). The MYCN amplification group had lower OS and EFS rates than the MYCN nonamplification group, but the difference was not statistically significant (45% OS and 37.5% EFS vs. 33.3% OS and 16.6% EFS; P=0.67 and P=0.67, respectively). Cis-retinoic acid treatment for 12 months was a strong prognostic factor that could reduce mortality rates among HR-NB patients (HR, 0.27; 95% CI, 0.09-0.785; P=0.01). CONCLUSION: High-dose chemotherapy plus stem cell rescue followed by cis-retinoic acid for 12 months was well tolerated and could improve the survival rates of patients with HR-NB.

Epidemiology of cholangiocarcinoma: an update focusing on risk factors.

Cholangiocarcinoma is relatively rare, but high incidence rates have been reported in Eastern Asia, especially in Thailand. The etiology of this cancer of the bile ducts appears to be mostly due to specific infectious agents. In 2009, infections with the liver flukes, Clonorchis sinensis or Opistorchis viverrini, were both classified as carcinogenic to humans by the International Agency for Research on Cancer for cholangiocarcinoma. In addition, a possible association between chronic infection with hepatitis B and C viruses and cholangiocarcinoma was also noted. The meta-analysis of published literature revealed the summary relative risks of infection with liver fluke (both Opistorchis viverrini and Clonorchis sinensis), hepatitis B virus, and hepatitis C virus to be 4.8 (95% confidence interval [95% CI]: 2.8-8.4), 2.6 (95% CI: 1.5-4.6), and 1.8 (95% CI: 1.4-2.4), respectively - liver fluke infection being the strongest risk factor for cholangiocarcinoma. Countries where human liver fluke infection is endemic include China, Korea, Vietnam, Laos, and Cambodia. The number of infected persons with Clonorchis sinensis in China has been estimated at 12.5 million with considerable variations among different regions. A significant regional variation in Opistorchis viverrini prevalence was also noted in Thailand (average 9.6% or 6 million people). The implementation of a more intensive preventive and therapeutic program for liver fluke infection may reduce incidence rates of cholangiocarcinoma in endemic areas. Recently, advances have been made in the diagnosis and management of cholangiocarcinoma. Although progress on cholangiocarcinoma prevention and treatment has been steady, more studies related to classification and risk factors will be helpful to develop an advanced strategy to cure and prevent cholangiocarcinoma.

Retrospective study on the combination of desferrioxamine and deferasirox for treatment of iron-overloaded thalassemic patients: first evidence of more than 2 years.

Some iron-overloaded patients have problems being treated with iron chelators. We therefore retrospectively studied 7 iron-overloaded thalassemic patients. Within the same week, patients received 20 to 30 mg/kg/d of oral deferasirox for 4 consecutive days, then a subcutaneous infusion of 20 to 40 mg/kg/d of desferrioxamine for 8 to 12 hours on the next 3 consecutive days. The median treatment duration was 25 months (range, 8 to 32). All of the patients showed a decrease in serum ferritin without any side effects. The protocol, combining deferasirox and desferrioxamine in sequence, was effective and safe: more cases should be studied.

Risk factors for colon cancer in Northeastern Thailand: interaction of MTHFR codon 677 and 1298 genotypes with environmental factors.

BACKGROUND: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colon cancer risk and possible interactions with environmental factors in a population from northeastern Thailand. METHODS: This hospital-based case-control study was conducted during 2002-2006; 130 colon cancer cases and 130 age- and sex-matched controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction with restriction fragment length polymorphism techniques. Associations between variables of interest and colon cancer were assessed using conditional logistic regression. RESULTS: Increased risk of colon cancer was associated with alcohol consumption and bowel habits. Alcohol drinkers who consumed < or = 0.50 or >0.50 units of alcohol per day had elevated risks (OR(adj) = 3.5; 95% CI: 1.19-10.25 and OR(adj) = 1.71; 95% CI: 0.74-3.96, respectively). The risk was also higher in subjects with frequent constipation (11.69; 2.18-62.79) and occasional constipation (3.43; 1.72-6.82). An interaction was observed between the MTHFR C677T polymorphism and freshwater fish consumption on colon cancer risk (P value for interaction = 0.031). Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively). CONCLUSIONS: In a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were also observed.

Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand.

Hb E-beta-thalassemia is the most common form of beta-thalassemia found in Thailand. The disease exhibits a varied clinical expression ranging from severe transfusion dependence to relatively mild thalassemia intermedia. We evaluated the effects of primary and secondary genetic factors in modulating the hematological and clinical presentation of 148 northeast Thai patients including 103 severe thalassemia major (TM) and 45 thalassemia intermedia (TI). Among 148 cases examined, eleven different mutations including two novel ones; (beta(33/34 (-G)) and beta(IVS2#815 C-T)) were identified in trans to the beta(E) gene in two TM cases. The other 9 known mutations included beta(41/42), beta(17), beta(IVS2#654), beta(-28), beta(71/72), beta(35), beta(IVS1#5), beta(IVS1#1) and beta(41). Except for the beta(-28) mutation which was found only in the TI group, others mutations were identified in both TM and TI. Co-inheritance of alpha-thalassemia as a phenotype modulating factor was not evident in this study, nor was the presence of the -158 (G)gamma-globin Xmn I polymorphism. Further analysis of the polymorphic (TG)n(CG)m repeats within the IVS2 of the two gamma-globin genes revealed no different proportions of the polymorphic patterns among TM and TI groups of patients either. Our data reveals that in the majority of these Hb E-beta-thalassemia patients, it is very hard to predict the clinical phenotype of the patients from the beta-globin mutations and these secondary genetic modifiers.

Risk Factors for Cholangiocarcinoma in Thailand: A Systematic Review and Meta-Analysis

Background and objective: Cholangiocarcinoma remains a serious public health concern in Thailand. While many of the risk factors for cholangiocarcinoma in western countries are well-recognized, it remains unclear whether they are the same in Thailand. We set out to investigate the risk factors for cholangiocarcinoma in Thailand. Methods: Starting March 4, 2016, we reviewed studies found using pre-specified keywords on SCOPUS, Pro Quest Science Direct, PubMed, and online public access catalog of Khon Kaen University. Two review authors independently screened studies for inclusion criteria, extracted data, and assessed the studied Risk of Bias. The Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Tools were used to assess the quality of included studies. The risk effects of factors were estimated as a pooled adjusted odds ratio with a 95% confidence interval. The heterogeneity of results was considered using the I-square, Tau-square and Chi-square statistics. Results: A strong association was found between cholangiocarcinoma and age, Opisthorchis viverrini infection, eating raw cyprinoid fish, family history of cancer, liquor consumption, and taking praziquantel. There was only a mild association found between eating nitrite-containing foods, fresh vegetables, education, smoking behavior, and sex. No association was found between cholangiocarcinoma and eating fermented fish (Pla-ra), northeastern Thai or Chinese sausage, sticky rice, meat, chewing betel nut, or eating fruit. There were two protective factors including fresh vegetables consumption and education attainment. Conclusion: There are unique risk factors of cholangiocarcinoma in Thailand, including age, Opisthorchis viverrini infection, eating raw cyprinoid fish, family history of cancer, liquor consumption, and taking praziquantel.

H63D mutation of the hemochromatosis gene and serum ferritin levels in Thai thalassemia carriers.

We determined the prevalence of the H63D and the IVS5#1G-A HFE mutations in 370 (169 males and 201 females) Thai thalassemia carriers and 201 normal subjects. While no IVS5#1G-A mutation was found, the H63D heterozygosity was identified in 5.5% (11/201) of normal subjects and 7.3% (27/370) of thalassemia carriers. Within the thalassemic group, the medians (ranges) of serum ferritin were 217.5 ng/ml (20.1-424.3) and 169.8 ng/ml (3.9-3,536.0) in male subjects and 30.4 ng/ml (11.9-130.7) and 49.3 ng/ml (0.6-931.0) in female subjects with (HD) and without (HH) H63D mutation, respectively. The proportions of subjects with elevated ferritin were found to be 37.5% (6/16) for HD and 14.0% (18/129) for HH in male and 0% (0/11) for HD and 3.0% (5/164) for HH in female subjects, respectively. Statistical analysis of all the data revealed no significant difference. Among 14 Hb E/beta-thalassemia patients, no difference in hematological data as well as serum ferritin levels was observed between those with (HD) and without (HH) H63D mutation. Therefore, the H63D heterozygosity has no significant effect on the serum ferritin level and screening for this HFE mutation in thalassemic patients is not recommended.

Joinpoint Analysis Trends in the Incidence of Colorectal Cancer in Khon Kaen, Thailand (1989 ­ 2012)

Objective: This study focused on recent changes in the incidence of colorectal cancer (CRC) in Khon Kaen, Thailand. Methods: Data for CRC over the period 1989 to 2012 from the population-based cancer registry of Khon Kaen province were employed. Age-standardized incidence rates (ASR) were calculated and classified into 4 age-groups for comparison. Joinpoint regression analysis was used to detect changes in trends among each line segment and an overall line was generated, whether increasing or decreasing, with annual percent change (APC) and average annual percent change (AAPC). Results: There were 3,364 CRC cases included in the analysis, 72.2% histological confirmed and 53.5% in men. Trends of ASRs generally demonstrated gradual increase over the period 1989 to 2012. For those aged under 45 or 50 years there was slight overall increase, with a somewhat zigzag pattern. From joinpoint analysis, the trends of all aged groups were found to be increasing among both men and women: aged 45 years and older group AAPC=3.40, 2.30 and 3.90, respectively); aged 50 years and older group AAPC=2.90, 2.20 and 3.40; aged under 45 years AAPC=6.30, 6.00 and 6.90; and aged under 50 years (AAPC=5.70, 3.20 and 5.70. Conclusions: ASRs for CRC have been gradually increasing in the northeast region of Thailand. Future studies should consider the subsite distribution.

Cancer incidence trends in Thailand, 1989-2000.

Through 2004, five cancer registries in Thailand have collected data for more than ten years. Three-year cancer incidence in Thailand covering the years 1989-1997 has been regularly reported in three volumes of 'Cancer in Thailand. Since the data for the last decade of the 20th century have been collected, the trends in incidence of some cancer sites were analyzed. Data sources were registry data from Chiang Mai, Lampang, Khon Kaen, Bangkok, and Songkhla, which are representative of the four major geographic regions of Thailand. The data drawn in 2002 covered the years 1989 to 1997 for Bangkok, the other four registries drew data from 1989 to 2000. The population denominators were estimated from the two censuses in 1990 and 2000. Only cancers of the liver, lung, colon-rectum, female breast, uterine cervix, and all cancer sites were analyzed since cancers of these sites may have major public health impacts. Age-specific incidence rates of different 5-year age groups were projected through the period 2007-2009 using a linear regression model if the rates were increasing, and a log-linear model to prevent prediction of a negative rate if the rates were decreasing. During the past decade, colorectal and breast cancers showed a statistical significant increasing trend, while the trend was generally stable for cancer of other sites. The number of new cancer cases of all sites is expected to be approximately 125,000 by the year 2008, compared with 81,000 in 1999. However, the accuracy of projections depends very much on the quality of the cancer registries' data. The Bangkok registry significantly improved case ascertainment in recent years, while the Chiang Mai registry had a consistent drop in incidence of cancer at many sites. In-depth investigation of some cancer sites and age period cohort modeling are required for better understanding of cancer trends in Thailand.