A prospective study of diet, lifestyle, and genetic factors and the risk of cancer in Khon Kaen Province, northeast Thailand: description of the cohort.

Cohort studies are the preferred design in observational epidemiology, but few involving the general population have been performed in Asia, and most concern affluent urban populations. The Khon Kaen study has recruited about 25,000 subjects, aged mainly 35-64, from villages in the relatively underdeveloped north-east of Thailand. All subjects underwent simple physical examination, completed an interviewer-administered questionnaire (including sections on lifestyle, habits, and diet) and donated specimens of blood, which were processed and stored in a biological bank at -20 degrees C. Female subjects (about 16,500) were offered screening by Pap smear, and specimens of cells from the cervix were stored at -20 degrees C. This paper describes the methodology of the study, and the characteristics of the participants. Almost all subjects are peasant farmers, with low annual income and body mass, although 14.6% of women had a BMI in the obese range (>30 kg/m(2)). Smoking was common among men (78% regular smokers, most of whom used home-produced cigarettes), but rare among women. Fertility levels were relatively high, with a more than half the women having four or more live births. 23.4% of subjects were infected with the liver fluke Opisthorchis viverrini, known to be highly endemic in this region. Follow-up of the cohort is by record-linkage to the provincial cancer registry. By 2003, 762 cancer cases had occurred, the most common being cancers of the liver (363 cases) and cervix uteri (44 cases). The antecedents of these cancers are being investigated using a nested case-control approach. The cohort will yield increasing numbers of cancers for study in the next decade, giving important information on the relative importance of dietary and lifestyle factors in a rural population, undergoing gradual transition to a more westernised lifestyle.

Illness experience and coping with gynecological cancer among northeast Thai female patients.

This quantitative and qualitative study describes the illness experience and the coping mechanisms of cervical cancer patients. Interviews were performed with 208 cervical cancer patients to determine their health seeking behavior and illness beliefs. Most began their treatment at local health services and district hospitals, and sought treatment in up to four different places before coming to the University Hospital. Most of the respondents were not sure about the cause of cervical cancer, and waited to see their symptoms before seeking treatment. Most perceived their condition as at an early stage. The qualitative research consisted of interviews with 79 selected patients and identified stigmatization from family and community members, problems with sexuality, and varied belief in meaning and causation of the disease. Many of the problems faced were coped with because of support from husbands, family and the community. It is recommended that better recording of patient data would allow a better follow-up service, and improved information for relatives would help them to understand the patient's problems, with both of these contributing to a better recovery environment for patients.

Promotion of the health of rural women towards safe motherhood--an intervention project in northeast Thailand.

An intervention project focusing on the health of women in the reproductive age was conducted in three districts of Khon Kaen Province, northeast Thailand between 1991 and 1996. Main emphasis was placed on improving reproductive health, the nutritional status including the iron deficiency anemia (IDA) as well as iodine deficiency disorders (IDD), and the parasitic diseases liver fluke (Opisthorchis viverrini) and hookworm. For implementation a community based Primary Health Care approach was used including the training of health officials in health matters, primary health care workers and villagers as well as enhancing health education and the dissemination of health information. The health delivery system was encouraged to take appropriate actions such as in the treatment of parasitic diseases and the control of IDA and IDD. Monitoring was done on a regular basis. The outcome of the project was assessed by comparing baseline data compiled from a random sample of the target population with the results of the final evaluation. An attempt to compare results obtained from villages within and outside of the project area failed most probably because of spill over effects. A number of important indicators on family planning and mother and child health care improved during the time the project was implemented; this included practising family planning, and participation in antenatal care. Also the proportion of females becoming pregnant for the first time when 20 years or older increased. Child-raising also improved in that almost all females gave colostrum to their babies by this time. Almost 75% of the women breast-fed their children. Improvements occurred in the nutritional status as far as the micronutrients iron and iodine were concerned, however the overall nutritional status of females did not change, but a rather high proportion of females were found to be overnourished. The project failed in reducing abortion and the proportion of females becoming pregnant when they are 18 years old or younger. It was also not possible to improve the usage of postnatal care. As anticipated, the results achieved so far are most suitable in serving as a training ground and providing a favorable example to improve family planning, mother- and child health care, and also the general health of females in the region, particularly in neighboring countries such as Lao PDR, Cambodia and Vietnam.

A self-administered device for cervical cancer screening in northeast Thailand.

OBJECTIVE: To test a self-scraping device as a mass screening device against a routine scraping method and to evaluate the acceptance of the self-scraping device by a group of rural females from Northeast Thailand. STUDY DESIGN: From a rural area of Northeast Thailand, 552 women were trained and motivated, through primary health care structures, to participate in a cervical cancer screening exercise using a self-scraping device. After one week, the same females were reexamined by gynecologists using the routine scraping method. In both cases the specimens were stained according to Papanicolaou. Through questionnaires the acceptance of the self-scraping device was evaluated. RESULTS: Through the self-scraping method, 13 cases suspicious for malignancy were detected. Specimens obtained through examination by physicians confirmed 11 cases to be suspicious for malignancy. No false negative cases were found. In the detection of inflammation, the self-scraping method was not as accurate as examination by a physician. The device was accepted by the females who participated in the study. CONCLUSION: In the rural areas of developing countries, where physicians and other trained medical personnel are not often available to carry out regular screening tests on a population basis, the self-scraping method can be applied as an integral part of primary health care for mass screening for uterine cervical cancer.

Incidence of childhood cancer in Thailand 1988-1991.

Incidence rates of cancers of childhood in Thailand are presented for the first time, and compared with results from cancer registries in Asia, Europe and the USA. As elsewhere in the world, leukaemia (principally acute lymphocytic), brain tumours and lymphomas comprise two-thirds of all childhood neoplasms. Carcinomas are rare, but the principal sites (liver, nasopharynx, thyroid and salivary gland) are extremely unusual elsewhere. Several features of the cancer pattern correspond to that in other Asian populations (China, Japan, Philippines), in particular the low incidence of Hodgkin's disease, Wilms' tumour and Ewing's sarcoma. Conversely, Burkitt's lymphoma is more common than elsewhere, although this may represent increasing awareness of this diagnosis amongst clinicians in recent years.

Cancer incidence in Thailand, 1988-1991.

Results from three cancer registries (Chiang Mai, Khon Kaen, and Songkhla) in different regions of Thailand and from a cancer survey in the population of Bangkok during the years 1988-1991 are presented, together with an estimate of the incidence of cancer for the country as a whole. Overall, liver cancer is the most frequent malignancy, but there are large regional differences in incidence and in histological type, with very high rates of cholangiocarcinoma in the northeast (associated with endemic opisthorchiasis) but a more even distribution of hepatocellular carcinoma. Lung cancer is second in frequency, with the highest rates in northern Thailand, where the incidence in women (Age Standardized Rate, 37.4 per 100,000) is among the highest in the world. A link with tobacco smoking is suggested by similarly raised rates, especially in women, for cancers of the larynx and pancreas. Cervical cancer is the most common malignancy in women, with relatively little regional variation in risk, while the incidence of breast cancer is low. Other cancer sites showing moderately increased rates include the lip and oral cavity, particularly in females from the north and northeast, where the chewing of betel nut remains common among older generations, nasopharyngeal cancer, carcinoma of the esophagus in the southern region, and penile cancer, especially in the north and northeast. Previous studies which have investigated the etiological factors underlying these patterns are reviewed, and the implications for future research and for national cancer control policies are discussed.

Cancer survival in Khon Kaen Province, Thailand.

Thailand is one of the few developing countries for which population-based cancer survival data are available. Using clinical follow-up information and reply-paid postal enquiries, 10,333 residents of Khon Kaen province registered with cancer in the period 1985-1992 were followed-up to the end of 1993. The sites of the most common cancers in the province were liver (5-year relative survival rate 9.2%), cervix (60.1%), lung (15.4%), breast (48.1%) and large bowel (41.9%). Results for Khon Kaen were compared with age-standardized survival data for the US and Scotland. Survival was consistently higher for US whites compared to Khon Kaen residents for those cancers whose prognosis is associated with early diagnosis (breast, cervix and large bowel) or the availability of intensive therapy (leukaemia and lymphoma). The main implication of these results for cancer control in Thailand is that the interventions of greatest potential benefit are those designed to promote early detection. More than one-third of all cancers in Thailand are liver tumours: primary prevention through control of hepatitis-B infection and liver fluke infestation is the only effective strategy for their control.

Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver.

Synergy between exposure to chemical carcinogens (nitrosamines) and infestation with the liver fluke Opisthorchis viverrini has been demonstrated in a hamster model of hepatocarcinogenesis (Flavell et al., Carcinogenesis 4:927-930, 1983; Thamavit et al., Carcinogenesis 8:1351-1353, 1987). To elucidate the mechanisms of this interaction we tested the hypothesis that liver parasitism might influence the expression and activity of carcinogen metabolizing enzymes. We found that one, and perhaps more, hamster liver cytochrome P450 (CYP) isozymes immunorelated to mouse CYP2A5 contributed up to 50 or 60% of the hepatic aflatoxin B1 (AFB) and N-nitrosodiethylamine (NDEA) metabolism, respectively. As inferred from average enzyme activities and from western blot, immunoinhibition, and substrate (coumarin) inhibition analyses, O. viverrini infestation increased the expression of enzymes detectable by anti-CYP2A5 antibody as well as NDEA metabolism in male but not in female hamsters. Immunohistochemical analysis of CYP2A expression by anti-mouse CYP2A5 antibody demonstrated that the O. viverrini-associated increase was not uniformly distributed throughout the liver but occurred in hepatocytes immediately adjacent to areas of inflammation. Immunohistochemical analysis of AFB-DNA adducts in the livers of O. viverrini-infested hamsters treated with AFB showed that the highest levels of adducts were found in the regions of liver where hepatocellular expression of enzymes detectable by anti-CYP2A5 antibody is induced. These results suggest that a high local expression of CYP isozymes in O. viverrini-infested livers could be a contributing risk factor in the development of liver cancers associated with parasitic hepatitis.

Parasite-associated morbidity: liver fluke infection and bile duct cancer in northeast Thailand.

Infection with the liver fluke, Opisthorchis viverrini, remains a major public health problem in Northeast Thailand, where approximately one-third of the population is infected. The northeast region is largely populated by Laos-descendent Thais who enjoy eating raw fish, which harbour the infective stage of the fluke. The parasite has maintained its presence in the population despite the widespread use of praziquantel and dissemination of health education material throughout the region by vigorous government-sponsored programs in recent years. The most severe consequence of liver fluke infection is cholangiocarcinoma, i.e. cancer of the bile duct epithelium. Although mortality due to the parasites alone appears to be uncommon, cholangiocarcinoma arising as a result of infection is one of the leading causes of death in the region. This paper reviews the pathogenesis of infection and the geographic, hospital-based and community studies which demonstrate the close relationship between infection and cancer. In addition, data from the Cancer Registry of Khon Kaen, Northeast Thailand and population-based studies using ultrasonography to visualize early tumours which illuminate the very high frequency of the cancer among heavily infected individuals and communities are discussed. Finally, the paper will close with a brief commentary on the prospects for control of the parasite and its likely impact on the frequency of cancer given the current epidemiological situation of liver fluke infection.

Increased nitrosamine and nitrate biosynthesis mediated by nitric oxide synthase induced in hamsters infected with liver fluke (Opisthorchis viverrini).

We previously reported that increased endogenous nitrosation in human subjects infected with the liver fluke Opisthorchis viverrini in north-east Thailand could be a risk factor for the development of cholangiocarcinoma. In the present study we examined our hypothesis that this increased endogenous nitrosation is mediated by nitric oxide (NO) synthase induced by O. viverrini infestation. Syrian golden hamsters experimentally infected with O. viverrini liver fluke excreted in the urine significantly greater amounts of nitrate, a stable oxidization product of NO, than untreated hamsters (3.64 +/- 0.86 versus 2.64 +/- 0.60 mumol/hamster/day, P < 0.001). When the rapidly nitrosatable thiazolidine 4-carboxylic acid was administered orally, the infected hamsters also excreted significantly elevated levels of N-nitrosothiazolidine 4-carboxylic acid than untreated hamsters (4.27 +/- 2.20 versus 2.33 +/- 1.13 nmol/hamster/day, P < 0.01), indicating that endogenous nitrosation is elevated in the animals with liver fluke. NO synthase activity measured in liver cytosol was about twice as high in the infected hamsters as in untreated animals. The enzyme, whose biochemical characteristics were similar to that induced in activated murine macrophages, was immunohistochemically localized in the cytoplasm of macrophages and eosinophils in the inflammation zone surrounding the parasite-containing bile ducts. These results support our hypothesis that, in fluke-infected subjects, NO synthase induction leads to excess production of NO and the observed elevated endogenous nitrosation. Since high concentrations of NO exert cytotoxic and mutagenic effects per se, excess NO produced in chronically infected/inflamed tissues may also play a role in initiation and subsequent modulation stages of cholangiocarcinoma development.

Unit cost analysis in a university hospital: an example from Srinagarind Hospital, Khon Kaen.

This is the first analytic study to identify the unit cost in the University Hospital using the standard method of analysis in health economics. The unit costs in the report can be used to calculate the cost of each service for any disease. The costs of the hospital administration cost center and the supportive cost center were both allocated to the patient care service center by the simultaneous allocation method. The cost of teaching personnel was excluded from the analysis because it is quite difficult to estimate and differentiate the ratio of teaching costs to service costs. The hotel cost of the inpatient ward varied from 77.81 baht to 604.7 baht per day. The unit cost per service per day is different from the charge which is presently used at Srinagarind Hospital. Some services, such as in-house transportation are not included in the charge. This study was conducted to identify the unit cost of each service. The decision to establish charges can depend partly on this data and partly on the administrator's judgement. Other factors, such as patient poverty can dictate the final decision. In any case, the hospital and health service center should identify their own unit costs to be able to plan for effective budget management.

Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.

Cholangiocarcinoma is a relatively rare cancer; worldwide it accounts for an estimated 15% of liver cancers. In most areas, the etiology is rather obscure, and identified risk factors such as hepatolithiasis, inflammatory bowel disease, and exposure to Thorotrast can account for only a small proportion of cases. In certain areas of southeast and eastern Asia, however, incidence rates are very high, and here there is a strong association with infection with the liver flukes Clonorchis sinensis and Opisthorchis viverrini. The mechanisms of carcinogenesis in O. viverrini infection have been the subject of considerable research; it seems that the presence of parasites induces DNA damage and mutations as a consequence of the formation of carcinogens/free radicals and of cellular proliferation of the intrahepatic bile duct epithelium. Preventive strategies in areas endemic for liver flukes appear straightforward, but breaking the cycle of infection has proved difficult in practice.

Cervical cancer in Khon Khaen University Hospital, Thailand 1985-1990.

From 1985 to 1990, 3040 patients with carcinoma of the uterine cervix were diagnosed and treated at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. The epidemiological aspects including ages and geographical distributions, histology, stages, treatment and outcome were presented and compared with those of the previous report.

Environmental risk factors for nasopharyngeal carcinoma: a case-control study in northeastern Thailand.

A case-control study of nasopharyngeal carcinoma was conducted in northeast Thailand, a region which shows an intermediate risk for this neoplasm. The study was conducted to investigate the importance of environmental exposures, particularly salted fish consumption, cigarette smoking, alcohol drinking, and occupational exposure to smoke or dust, as risk factors for the disease. Data from 120 nasopharyngeal cancer cases and the same number of hospital-matched controls indicated that consumption of sea-salted fish at least once a week was a significant risk factor (odds ratio, 2.5; 95% confidence interval, 1.2-5.2). Agricultural workers were also at significantly higher risk (odds ratio, 2.8; 95% confidence interval, 1.3-6.2), and working in agriculture or as a woodcutter was associated with an even higher risk (odds ratio, 8.0; 95% confidence interval, 2.3-28.2). There was no association between nasopharyngeal carcinoma and alcohol drinking or cigarette smoking.

Ukrain both as an anti cancer and immunoregulatory agent.

Thirty six stage III cancer patients were treated with Ukrain, a semisynthetic drug derived from Chelidonium majus L. alkaloids conjugated with thiophosphoric acid. The drug was injected intravenously every second day in a dose of 10 mg per injection. Each patient received 300 mg of the drug (30 injections). The cytostatic effect of Ukrain was monitored clinically and by ultrasonography (USG) and computer tomography (CT), as well as by determination of CEA and CA-125 in the sera of patients with rectal and ovarian cancers, respectively. The influence of Ukrain on immune parameters was evaluated by monoclonal antibodies (MAb) to CD2, CD4, CD8 and CD22. The influence of Ukrain on immune parameters in cancer patients was matched with its effect on these parameters in 20 healthy volunteer controls. The results obtained indicate that Ukrain, in a concentration not cytostatic in normal cells, is cytostatic for malignant ones, and may suppress the growth of cancer. The compound also has immunoregulatory properties, regulating the T lymphocyte subsets.

The effects of thiophosphoric acid (Ukrain) on cervical cancer, stage IB bulky.

This study was carried out to determine the clinical and immune response of a stage IB voluminous uterine cervical cancer to thiophosphoric acid alkaloid derivatives from Chelidoniium majus L. (Ukrain). The drugs were administered 10 mg intramuscularly every other day, for up to 10 injections. The two largest diameters and tumour volumes were measured and laboratory and immunological tests were performed before and after Ukrain administration. The patients were then operated on with type III Piver's radical hysterectomy. Three out of nine eligible cases had partial responses while six cases remained stable. Decreased total B lymphocytes and suppressor T lymphocytes were observed as well as increased total numbers of T lymphocytes and helper T lymphocytes. There was no single case of clinical or haematological toxicity apart from mild nausea. Two patients were treated with adjuvant radiotherapy due to lymphatic involvement and all nine patients were still alive at least six months after follow-up.

A high incidence of liver cancer in Khon Kaen Province, Thailand.

Based on a population-based cancer registry in Khon Kaen Province, Thailand, data were collected actively and passively from all hospitals, health centers and the office of the Chief Medical Officer of Khon Kaen. The data were collected prospectively for the year 1988 and retrospectively for the years 1985-1987. Liver cancer, especially cholangiocarcinoma, was the leading cancer in both sexes. The age-standardized incidence rates for the year 1988 were 89.2/10(5) in males and 35.5/10(5) in females respectively, which are among the highest rates recorded in the world. The number of reported liver cancer cases increased each year. The observed geographical clusters of liver cancer appear to be associated with the prevalence and intensity of Opisthorchis viverrini infection, as reported in previous studies in this area.

Epidemiology of cancer in Khon Kaen.

The prospective and retrospective data collection of cancer cases in all the hospitals and death certificates in Khon Kaen province were reported as a population-based cancer registry of Khon Kaen province. Liver cancer especially cholangiocarcinoma and cervical cancer lead the group. The age-standardized incidence rate of cancer of Khon Kaen was about 72.4 to 173.3 per 100,000 population per year and it is higher in males than in females.