Ming-Fang Yen

Beyond Randomized Controlled Trials Organized Mammographic Screening Substantially Reduces Breast Carcinoma Mortality

The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so‐called “service screening“) faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties.

A novel method for prediction of long-term outcome of women with T1a, T1b, and 10–14 mm invasive breast cancers: a prospective study

BACKGROUND Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes. METHODS We prospectively applied mammographic classifications of tumour type to a consecutive series of 343 mammograms of invasive breast cancers of size 1-14 mm. Classifications were: stellate (spiculated) mass with no calcifications; circular or oval lesions with no calcifications; spiculated or circular lesions with non-casting-type calcifications; and casting-type calcifications. FINDINGS 20-year survival for women with 1-14 mm invasive tumours with casting-type calcifications was 55%. 14% of 138 women with 1-9 mm tumours had casting-type calcifications on mammography, which accounted for 73% of all breast-cancer deaths (p<0.001). T1a, T1b, and 10-14 mm tumours with casting-type calcifications behaved as if they were larger lesions, since the rate of death was similar to that for women with advanced high-grade tumours. Most women who died were node-negative. The long-term survival of women who had tumours of 1-9 mm with no casting-type calcifications was about 95%. INTERPRETATION Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.

A case-cohort study for the disease natural history of adenoma-carcinoma and de novo carcinoma and surveillance of colon and rectum after polypectomy: implication for efficacy of colonoscopy.

The disease natural history of colorectal neoplasm regarding two opposing theories, adenoma–carcinoma sequence and de novo carcinoma theory, is controversial and rarely quantified. The aims of this study are therefore to estimate the dwelling times of adenoma–carcinoma sequence by adenoma size and histological type, taking de novo carcinoma into account. The efficacy of polypectomy was therefore estimated making allowance for two pathways. A case–cohort design, underpinning a cohort with 13 908 subjects (including 10 496 normal subjects, 2652 polyps, 760 colorectal cancers) who underwent the first examination of colonoscopy between 1979 and 1998, was devised to estimate parameters associated with two opposing theories by randomly selecting 305 normal subjects, 300 patients with polyps, and 116 colorectal cancers from the cohort. All the 2652 polyps were linked to national cancer registry to ascertain 25 invasive carcinomas after polypectomy. For the five-state model associated with adenoma size, dwelling times of small (0.6–1 cm) and large adenoma (>1 cm) are 7.75 and 5.27 years for the model without considering de novo, and 17.48 and 15.90 years for the model taking de novo carcinoma into account. Similar findings are observed for the model associated with histological type. The estimated proportions of de novo carcinoma are 31.87% from the model by adenoma size and 27.81% from the model by histological type. Compared to size less than 5 mm, patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold (0.67–10.74) and 4.25-fold (1.23–14.70), respectively, for the risk of malignant transformation. There are similar findings for the model by histological type. The estimates of overall efficacy of colonoscopy in reducing CRC is 73% for the model allowing for de novo carcinoma and 88% for the model without considering de novo carcinoma theory. The efficacy of diminutive adenoma and small adenoma increases with follow-up years, whereas the efficacy of large adenoma decreases with follow-up years. In conclusion, about 30% of cancers arising from de novo sequence are demonstrated. This finding, together with the adenoma–carcinoma sequence associated with adenoma size and histological type, is important for the estimation of dwelling times, the efficacy of colonoscopy, and the surveillance of polyp after polypectomy.

Community-based multiple screening model†‡§¶

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

Prevalence, incidence, and mortality of PD: A door-to-door survey in Ilan County, Taiwan

Background: The reported prevalence and incidence rates of PD were significantly lower in China than those in Western countries. People in China and Taiwan have a similar ethnic background. Objective: To investigate the prevalence, incidence, and mortality rate of PD in Taiwan. Method: The authors conducted a population-based survey using a two-stage door-to-door approach for patients aged 40 years or older in Ilan, Taiwan. Patients were diagnosed with PD by having at least two of the four cardinal signs of parkinsonism and exclusion of seconddary parkinsonism. To identify new cases of PD after the survey, patients with negative results of parkinsonism in the first stage were matched to the information on clinical diagnosis of PD from the Bureau of National Health Insurance toward the end of December 31, 1997. All cases of PD were linked to the Taiwan mortality registration to ascertain causes of deaths until December 31, 1999. Results: The participation rate was 88.1% among the 11,411 contacted individuals. Thirty-seven cases of PD were identified. The age-adjusted prevalence rate of PD for all age groups was 130.1 per 100,000 population after being adjusted to the 1970 US census, assuming no cases of PD would be found among those younger than 40 years of age. Of 9972 non-PD subjects in the first screen, 15 new cases of PD were ascertained. The age-adjusted incidence rate was 10.4 per 100,000 population for all age groups. The case fatality rate of PD after a 7-year follow-up was 40.4% (21 deaths in 52 patients with PD). The relative risk of death for PD cases versus non-PD cases was 3.38 (95% CI: 2.05–4.34). The 5-year cumulative survival rate in PD cases (78.85%) was statistically lower than that in non-PD cases (92.84%). Conclusion: The prevalence and incidence rates of PD in Taiwan were much higher than those reported in China, but closer to those in Western countries. These results suggest that environmental factors may be more important than racial factors in the pathogenesis of PD.

Community-based multiple screening model: design, implementation, and analysis of 42,387 participants.

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point

BACKGROUND: It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials, and that disease specific mortality is biased in favour of screening. This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials, and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening. METHODS: We used data from the Swedish Two-County Trial of mammographic screening for breast cancer, in which 77 080 women were randomised to an invitation to screening and 55 985 to no invitation. We estimated relative risks (RRs) (invited v control) of death from breast cancer, death from other causes within the breast cancer cases, and death from all causes within the breast cancer cases. RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time. RESULTS: There was a significant 31% reduction in breast cancer mortality in the invited group (RR 0.69, 95% confidence interval (CI) 0.58–0.80; p<0.001). There was no significant increase in deaths from other causes among breast cancer cases in the invited group (RR 1.12, 95% CI 0.96–1.31; p=0.14). A significant 19% reduction in deaths from all causes was observed among breast cancer cases in the group invited to screening (RR 0.81, 95% CI 0.72–0.90; p<0.001). A more conservative estimation gave a significant 13% reduction (RR 0.87, 95% CI 0.78–0.97; p=0.01). These findings are consistent with the magnitude of the reduction in breast cancer mortality. CONCLUSIONS: Invitation to screening was associated with a reduction in deaths from all causes among breast cancer cases, consistent with high participation rates in screening. There is no significant evidence of bias in cause of death classification in the Two-County Trial, and as breast cancer mortality is the targeted clinical outcome in breast cancer screening, it is the appropriate end point in a breast cancer screening trial. All-cause mortality is a poor and inefficient surrogate for breast cancer mortality.

Mammographic tumour features can reliably predict the long-term outcome of women with 1–14 mm invasive breast cancer: suggestions for revision of current therapeutic practice and the TNM classification system

We studied the 24-year survival of 714 women with 1–14 mm invasive breast cancer according to mammographic features, including appearance of calcifications and masses. The most common mammographic feature was a stellate lesion with no associated calcifications (420 cases, 59%). Patients with stellate lesions had excellent long-term survival (95%). Casting-type calcifications were observed in 52 (7%) cases and were significantly associated with a positive lymph node status, poorer histological grade, and increased risk of breast cancer death (hazard ratio = 9.19, 95% confidence interval = 4.18–20.17). Except for tumours with casting type calcifications, all tumours less than 10 mm had excellent survival, regardless of node status, histological grade or treatment. For those with casting-type calcifications, survival was poorer even with 1–9 mm tumours (72% at 20 years). For 10–14 mm tumours, 20-year survival was 52% for those with casting calcifications, and 86–100% otherwise. Small invasive cancers accompanied by casting-type calcifications have unexpectedly poor prognosis for their size. Neoductgenesis offers a possible explanation for the unexpectedly poor outcome. There is a need to develop treatment protocols for this group. After exclusion of tumours with casting-type calcifications, the remainder have extremely good prognosis when treated with surgery and no adjuvant therapy.

Increased risk of trigeminal neuralgia after hypertension A population-based study

Objective: Very few studies have explored the temporal relationship between hypertension and trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether hypertension is associated with a higher risk of developing TN. Methods: A total of 138,492 persons with at least 2 ambulatory visits with the principal diagnosis of hypertension in 2001 were enrolled in the hypertension group. The nonhypertension group consisted of 276,984 age- and sex-matched, randomly sampled subjects without hypertension. The 3-year TN-free survival rate and the cumulative incidence of TN were calculated using the Kaplan-Meier method. Cox proportional hazard regression was used to estimate the hazard ratio of TN. Results: In the hypertension group, 121 patients developed TN during follow-up, while, in the nonhypertension group, 167 subjects developed TN. The crude hazard ratio for the hypertension group was 1.52 (95% confidence interval [CI] 1.20–1.92; p = 0.0005), while, after adjustment for demographic characteristics and medical comorbidities, the adjusted hazard ratio was 1.51 (95% CI 1.19–1.90; p = 0.0006). Conclusions: This study shows a significantly increased risk of developing TN after hypertension. Further studies are needed to elucidate the underlying mechanism of the association between hypertension and TN.

Assessing progression and efficacy of treatment for diabetic retinopathy following the proliferative pathway to blindness: Implication for diabetic retinopathy screening in Taiwan

Aims The natural history and treatment efficacy of diabetic retinopathy (DR) play important roles in the evaluation of screening. Therefore, the natural history of DR and rates of transition after treatment (including metabolic control and laser photocoagulation) from no diabetic retinopathy (NDR) to blindness were quantified.