Tony Hsiu-Hsi Chen

Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality during 3 Decades

PURPOSE To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects. MATERIALS AND METHODS This study was carried out under the auspices of the Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression. RESULTS There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk [RR] = 0.69; 95% confidence interval: 0.56, 0.84; P < .0001) and consensus data (RR = 0.73; 95% confidence interval: 0.59, 0.89; P = .002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up. CONCLUSION Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.

Psychosocial and psychiatric risk factors for suicide. Case-control psychological autopsy study.

BACKGROUND Few studies of suicide have simultaneously examined the individual and combined effects of psychosocial and psychiatric risk factors. AIMS To do so in a representative sample of suicides. METHOD A case-control psychological autopsy was conducted among 113 consecutive suicides and 226 living controls matched for age, gender, ethnicity and area of residence in Taiwan. RESULTS Five major risk factors (loss event, suicidal behaviour in first-degree relatives, ICD-10 major depressive episode, emotionally unstable personality disorder and substance dependence) were found to have independent effects on suicide from multivariate conditional logistic regression analysis. CONCLUSIONS Effective intervention and management for loss event and major depressive episode among emotionally unstable subjects with a family tendency of suicidal behaviour, frequently also comorbid with alcohol or other substance dependence, may prove to be most effective for suicide prevention in different populations.

Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England

Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years. Setting The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years. Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference. Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.

The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention

Objective To evaluate the benefit of mass eradication of Helicobacter pylori infection in reducing premalignant gastric lesions. Design Mass eradication of H pylori infection was started from 2004 for a Taiwanese population with prevalent H pylori infection, who were >30 years of age. Participants positive for the 13C-urea breath test underwent endoscopic screening and 1-week clarithromycin-based triple therapy. For subjects whose initial treatment failed, 10-day levofloxacin-based triple therapy was administered. The main outcome measures were changes in the prevalence of H pylori infection and premalignant gastric lesions, and changes in the incidence of premalignant gastric lesions and gastric cancer before (1995–2003) and after (2004–2008) chemoprevention using various comparators. Results The reduction in H pylori infection was 78.7% (95% CI 76.8% to 80.7%), and the estimated incidence of re-infection/recrudescence was 1% (95% CI 0.6% to 1.4%) per person-year. The effectiveness of reducing the incidence of gastric atrophy resulting from chemoprevention was significant at 77.2% (95% CI 72.3% to 81.2%), while the reduction in intestinal metaplasia was not significant. Compared with the 5-year period before chemoprevention and in the absence of endoscopic screening, the effectiveness in reducing gastric cancer incidence during the chemoprevention period was 25% (rate ratio 0.753, 95% CI 0.372 to 1.524). The reduction in peptic ulcer disease was 67.4% (95% CI 52.2% to 77.8%), while the incidence of oesophagitis was 6% (95% CI 5.1% to 6.9%) after treatment. Conclusions Population-based eradication of H pylori infection has led to a significant reduction in gastric atrophy at the expense of increased oesophagitis. The ultimate benefit in reducing gastric cancer incidence and its mortality should be validated by a further long-term follow-up. Trial registration number NCT00155389.

Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection

This study aimed to elucidate the relationship of type 2 diabetes, other known risk factors, and primary hepatocellular carcinoma (HCC) in countries with a high prevalence of hepatitis infection. We followed a prospective cohort of 54,979 subjects who participated in the Keelung Community‐Based Integrated Screening program between 1999 and 2002. A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level, and a total of 138 confirmed HCC cases were identified either through two‐stage liver cancer screening or linkage with the National Cancer Registry. The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model. After controlling for age, sex, hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and alcohol consumption, the association between type 2 diabetes and incidence of HCC (excluding 33 prevalent cases identified at enrollment) was modified by HCV status and cholesterol level. The associations were only statistically significant (adjusted hazard ratio [HR] = 2.08 [1.03‐4.18]) for being HCV negative and for having hypercholesterolemia (adjusted HR = 2.81 [1.20‐6.55]). These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment. In conclusion, in an area with a high prevalence of hepatitis virus infection, type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol. (HEPATOLOGY 2006;43: 1295–1302.)

Breast Cancer in Limited-Resource Countries: Early Detection and Access to Care

Abstract:  Although incidence, mortality, and survival rates vary fourfold in the worlds regions, in the world as a whole, the incidence of breast cancer is increasing, and in regions without early detection programs, mortality is also increasing. The growing burden of breast cancer in low‐resource countries demands adaptive strategies that can improve on the too common pattern of disease presentation at a stage when prognosis is very poor. In January 2005, the Breast Health Global Initiative (BHGI) held its second summit in Bethesda, MD. The Early Detection and Access to Care Panel reaffirmed the core principle that a requirement at all resource levels is that women should be supported in seeking care and should have access to appropriate, affordable diagnostic tests and treatment. In terms of earlier diagnosis, the panel recommended that breast health awareness should be promoted to all women. Enhancements to basic facilities might include the following, in order of resources: effective training of relevant staff in clinical breast examination (CBE) both for symptomatic and asymptomatic women; opportunistic screening with CBE; demonstration projects or trials of organized screening using CBE or breast self‐examination; and finally, feasibility studies of mammographic screening. Ideally, for complete evaluation, such projects require notification of deaths among breast cancer cases and staging of diagnosed tumors.

Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk group in Taiwan.

Although previous studies have demonstrated the ability of ultrasonography (US) screening to detect small asymptomatic hepatocellular carcinoma (HCC), the efficacy of US screening in reducing deaths from HCC still remained unresolved. A 2‐stage screening program was designed to identify a high risk group in 7 townships in Taiwan by 6 markers (of risk for HCC) and repeated US screening was further applied to those with at least 1 positive result for the 6 markers, with a range of 3‐ to 6‐month inter‐screening intervals to those with liver cirrhosis or other chronic liver diseases and an annual screening regime for the remaining subjects with normal findings according to US. The 4,843 subjects in this cohort were followed up for an average of 7 years. We compared 4,385 attenders with 458 non‐attenders, in conjunction with baseline assessment for self‐selection bias. In addition, we assessed baseline variables with respect to their effects on risk of incidence of and mortality from HCC and on risk of incidence of liver cirrhosis. The difference in mortality between attenders and non‐attenders was then re‐estimated adjusting for significant predictors of cirrhosis, HCC incidence and HCC death as a further guard against baseline differences between attenders and non‐attenders in risk profiles. Results of US screening for this high risk group found the mortality was lower by 24% (95% CI: −52 to 62%) in the attenders compared to the non‐attenders. After adjustment for sensitivity, the mean sojourn time (MST) were 1.57 (95% CI: 0.94–4.68) for subjects with liver cirrhosis and 2.66 (95% CI: 1.68–6.37) years for non‐cirrhotic patient. Significant increases in risk of HCC incidence were associated with increasing age, male gender, hepatitis B surface antigen positive (HbsAg), hepatitis C antibody positive (Anti‐HCV), high levels of alanine transaminase (ALT) and alpha‐fetoprotein (AFP) and a family history of HCC. Significantly increased risks of liver cirrhosis were associated with predictors of cirrhosis were increasing age, HbsAg, high levels of ALT and of AFP. Significant or borderline significant increases in risk of HCC death were associated with increasing age, male gender, HbsAg, high levels of AST and AFP. Adjusted for the significant variables, the mortality was lower by 41% (95% CI: −20 to 71%, p = 0.1446) in the attenders compared to the non‐attenders. The present study provides suggestive evidence on the efficacy of US screening in a selective high risk group in an endemic area of hepatitis B. A randomized controlled trial would yield definitive evidence. Within the protocol of such a trial, a shorter interscreening interval for patients with liver cirrhosis is suggested.

Prevention of Hepatocellular Carcinoma by Universal Vaccination against Hepatitis B Virus: The Effect and Problems

Purpose: In spite of the success of hepatitis B immunization, still a significant proportion of childhood hepatocellular carcinoma (HCC) failed to be prevented by the hepatitis B immunization program. This study is aimed to investigate the problems in the HCC prevention in children. Experimental Design: All HCC children ages 6 to 14 diagnosed between 1981 and 2000 in Taiwan were collected from two national childhood HCC registry systems. We analyzed the causes of HCC prevention failure and the risk ratio of HCC among hepatitis B carriers born before versus after the vaccination program. Results: The incidence of HCC per 100,000 children declined from 0.54 to 0.20 in those born before versus after the vaccination program (risk ratio, 0.36). Vaccine failure (33.3-51.4%) and failure to receive hepatitis B immunoglobulin at birth (42.4-57.5%) were the main causes of HCC prevention failure. Mother-to-child transmission of hepatitis B virus infection is an important risk factor of HCC development. This is evidenced by the very high hepatitis B surface antigen seropositive rate in our HCC children (97%) and their mothers (96%). Hepatitis B carrier children born after the vaccination program had a higher risk of developing HCC than those born before the program (risk ratio, 2.3-4.5). Conclusions: Vaccine failure and failure to receive hepatitis B immunoglobulin are the main problems preventing eradication of HCC. Hepatitis B carrier children born after the immunization program have a higher risk of developing HCC than those born before.

Risk factors for leukoplakia and malignant transformation to oral carcinoma: a leukoplakia cohort in Taiwan

The effects of betel nut chewing, smoking and alcohol on the occurrence of leukoplakia and its malignant transformation to oral carcinoma were quantified in a leukoplakia cohort (n = 435) from one medical centre between 1988 and 1998 in Taiwan. Sixty oral carcinomas were ascertained in this cohort. A case–control study within the leukoplakia cohort was used to study, risk factors. Using the Weibull survival model, the incidence of malignant transformation of leukoplakia was shown to increase with follow-up years. After adjustment for other relevant risk factors, betel nut chewing (adjusted odds ratio (OR) = 4.59; 95% confidence interval (CI) 1.25–16.86) remained a significant risk factor for malignant transformation. Results from the case–control study showed that the adjusted odds ratios for betel nut chewing and smoking on the occurrence of leukoplakia were 17.43 (95% Cl 1.94–156.27) and 3.22 (95% Cl 1.06–9.78), respectively. Similar findings were observed when daily frequency and duration were taken into account. This implies that cessation of smoking may reduce by 36% leukoplakia cases, while elimination of betel nuts may prevent 62% of leukoplakia and 26% of malignant transformation to oral carcinoma in the underlying population.

A population-based study investigating the association between metabolic syndrome and Hepatitis B/C infection (Keelung Community-based Integrated Screening Study No. 10)

Objectives:We aimed to assess the association between metabolic syndrome (MS) and hepatitis B/C virus infection using a large population-based study.Design and methods:A population-based cross-sectional study design was adopted with a total of 53 528 subjects being enrolled from the integrated multiple diseases screening program in Keelung, Taiwan. Evidence of past hepatitis B/C infection, acquired during childhood or as a young adult, was identified during the two-stage liver cancer screening part of the process. Information on biochemical markers and anthropometric measures related to MS, such as fasting blood sugar, triglyceride and high-density lipoprotein (HDL), abdominal circumference and blood pressure (BP), were collected routinely while screening for hypertension, type 2 diabetes, and hyperlipidemia. Logistic regression was used to estimate odds ratios and related 95% confidence intervals for the associations between MS and hepatitis B/C infection.Results:High blood pressure (SBP⩾135 mmHg or DBP⩾85 mmHg) (adjusted odd ratio: 0.89 (0.83–0.94)) and high triglyceride (⩾150 mg/dl) (adjusted odds ratio: 0.65 (0.60–0.69)) were, after adjusting for gender and age, inversely associated with being HBsAg positive (P<0.05). The likelihood of developing MS was lower in the HBsAg positive than the HBsAg negative (adjusted odds ratio: 0.84 (0.76–0.93)). A positive association between being anti-HCV positive and having low serum HDL (male <40 mg/dl, female <50 mg/dl) was also noted (adjusted odds ratio: 1.61 (1.37–1.88) after controlling for gender and age). High triglyceride was inversely associated with being anti-HCV positive (adjusted odds ratio: 0.63 (0.55–0.71).Conclusions:There is an inverse association between MS and hepatitis B virus infection whereas the association was heterogeneous for HCV infection with a positive association with abnormal serum HDL but an inverse association with hypertriglyceridemia.