Areca Nut and Oral Cancer: Evidence from Studies Conducted in Humans.

Areca nut chewing is one of the major risk factors for oral cancer, with large-magnitude risks reported in studies comparing betel quid chewers and never users, and it has been evaluated as a group 1 carcinogen by the International Agency for Research on Cancer. Data from a high-quality meta-analysis examining risk estimates are presented in summary form with additional information from more recent studies (pooled adjusted relative risk, 7.9; 95% CI, 7.1 to 8.7). The risk of oral cancer increases in a dose-response manner with the daily number of quids consumed and the number of years chewing. In the Indian subcontinent and in Taiwan, approximately half of oral cancers reported are attributed to betel quid chewing (population attributable fraction, 53.7% for residents in Taiwan and 49.5% for the Indian population), a disease burden that could be prevented. Oral leukoplakia and oral submucous fibrosis are 2 main oral potentially malignant disorders caused by areca nut chewing that can progress to oral cancer with continued use. Ex-chewers seem to demonstrate lower risks than current chewers, but the impact of areca nut cessation on oral cancer risk has not been scientifically evaluated on the basis of randomized controlled studies. These data strongly reconfirm that betel quid chewing, primarily areca nut use, should be taken into account in assessing the cancer risk of South Asian, East Asian populations and Pacific Islanders for the development of oral cancer.

Chlorpyrifos is associated with slower serum cholinesterase recovery in acute organophosphate-poisoned patients.

PURPOSE: Organophosphate poisoning (OPP) accounts for 200,000 deaths annually in developing countries. Serum cholinesterase (SChE) is of diagnostic value in patients with OPP and is checked repeatedly during the course of treatment. This study aimed to investigate the recovery pattern in patients with OPP using linear mixed models. METHODS: Using a retrospective cohort study design, we included 212 adult OPP patients who had visited the emergency department (ED) in a tertiary medical center between 2000 and 2010. One hundred and thirty-one patients were available for analysis, as 81 patients did not meet the criteria and were excluded. Information regarding basic personal characteristics, initial vital signs and severity scores, laboratory data, type and amount of organophosphate ingested, treatment, and serial SChE values was collected. A random coefficient model with a random intercept and a random slope of time were added to address the dynamic relationships of SChE with time and other associated factors. RESULTS: The initial SChE activity and recovery rates varied among patients with OPP. The type of organophosphate, the first SChE activity, and the initial APACHE II score were significantly related to the SChE recovery trend. Chlorpyrifos and methamidophos had significantly slower and faster SChE recovery rates, respectively, than other organophosphates. Sex, dose of Pralidoxim (2-PAM), and delay in obtaining medical assistance did not significantly affect SChE recovery. CONCLUSIONS: This study demonstrated the pattern and associated correlates of SChE activity recovery in patients with acute OPP. Chlorpyrifos appeared to have a slower SChE activity recovery rate than other organophosphates.

Evaluation of mammographic surveillance services in women aged 40-49 years with a moderate family history of breast cancer: a single-arm cohort study.

BACKGROUND: Women with a significant family history of breast cancer are often offered more intensive and earlier surveillance than is offered to the general population in the National Breast Screening Programme. Up to now, this strategy has not been fully evaluated. OBJECTIVE: To evaluate the benefit of mammographic surveillance for women aged 40-49 years at moderate risk of breast cancer due to family history. The study is referred to as FH01. DESIGN: This was a single-arm cohort study with recruitment taking place between January 2003 and February 2007. Recruits were women aged < 50 years with a family history of breast or ovarian cancer conferring at least a 3% risk of breast cancer between ages 40 and 49 years. The women were offered annual mammography for at least 5 years and observed for the occurrence of breast cancer during the surveillance period. The age group 40-44 years was targeted so that they would still be aged < 50 years after 5 years of surveillance. SETTING: Seventy-four surveillance centres in England, Wales, Scotland and Northern Ireland. PARTICIPANTS: A total of 6710 women, 94% of whom were aged < 45 years at recruitment, with a family history of breast cancer estimated to imply at least a 3% risk of the disease between the ages of 40 and 50 years. INTERVENTIONS: Annual mammography for at least 5 years. MAIN OUTCOME MEASURES: The primary study end point was the predicted risk of death from breast cancer as estimated from the size, lymph node status and grade of the tumours diagnosed. This was compared with the control group from the UK Breast Screening Age Trial (Age Trial), adjusting for the different underlying incidence in the two populations. RESULTS: As of December 2010, there were 165 breast cancers diagnosed in 37,025 person-years of observation and 30,556 mammographic screening episodes. Of these, 122 (74%) were diagnosed at screening. The cancers included 44 (27%) cases of ductal carcinoma in situ. There were 19 predicted deaths in 37,025 person-years in FH01, with an estimated incidence of 6.3 per 1000 per year. The corresponding figures for the Age Trial control group were 204 predicted deaths in 622,127 person-years and an incidence of 2.4 per 1000 per year. This gave an estimated 40% reduction in breast cancer mortality (relative risk = 0.60; 95% confidence interval 0.37 to 0.98; p = 0.04). CONCLUSIONS: Annual mammography in women aged 40-49 years with a significant family history of breast or ovarian cancer is both clinically effective in reducing breast cancer mortality and cost-effective. There is a need to further standardise familial risk assessment, to research the impact of digital mammography and to clarify the role of breast density in this population. TRIAL REGISTRATION: National Research Register N0484114809. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 11. See the HTA programme website for further project information.

Differences between methicillin-resistant Staphylococcus aureus bacteremic isolates harboring type IV and type V staphylococcal cassette chromosome mec genes based on prior patient healthcare exposure.

This observational study enrolled adult patients with bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) who were treated at the emergency department of a teaching hospital from 2001 to 2007. MRSA isolates with type IV and type V staphylococcal cassette chromosome mec (SCCmec) genes (SCC IV/V-MRSA) were included in the final analysis. Healthcare-associated SCC IV/V-MRSA (HA-SCC IV/V-MRSA) and community-acquired SCC IV/V-MRSA (CA-SCC IV/V-MRSA) were defined as the identification of an SCC IV/V-MRSA isolate from a patient with and without healthcare-associated risk factors, respectively. Thirty-four cases of CA-SCC IV/V-MRSA (20 SCCmec type IV, 14 SCCmec type V) and 81 cases of HA-SCC IV/V-MRSA (59 SCCmec type IV, 22 SCCmec type V) bacteremia were identified. Vascular device-associated infections were a significant infection source in HA-SCC IV/V-MRSA bacteremia cases. SCCmec type IV HA-SCC IV/V-MRSA isolates (3.4%) were significantly less likely to carry the Panton-Valentine leukocidin (PVL) gene than SCCmec type IV CA-SCC IV/V-MRSA isolates (35.0%, p = 0.001). The 90-day cumulative probability of survival was 76% for patients with CA-SCC IV/V-MRSA bacteremia and 66% for patients with HA-SCC IV/V-MRSA bacteremia (p = 0.247, by the Wilcoxon rank-sum test). Significant differences in antimicrobial susceptibility were observed between bacterial isolates from patients with CA-SCC IV/V-MRSA bacteremia and HA-SCC IV/V-MRSA bacteremia.

Changes in peripheral blood lymphocyte phenotypes distribution in patients with oral cancer/oral leukoplakia in Taiwan.

Oral squamous cell carcinoma (OSCC) is common in many Asian countries. The immunopathogenesis of OSCC is unclear. The authors analyzed the lymphocyte subtypes and surface activation markers in healthy Taiwanese people (n=130) and patients with OSCC (n=97)/oral leukoplakia (OL, n=28) using flow cytometry. Univariate analysis found an elevation in the percentage of CD56+ NK cells, CD4+/CD69+ T cells, CD19+/CD69+ B cells and CD56+/CD69+ NK cells in OSCC patients relative to healthy people. The CD19+ and CD19+/CD25+ lymphocyte subtypes decreased in OSCC patients. CD56+ NK cells increased in OL patients. CD56+/CD69+ NK cells were elevated in recurrent and advanced OSCC. Multivariate analysis revealed an increase in CD56+ NK and CD19+/CD69+ cells in OL patients relative to controls. CD19+ B cells declined during progression from OL to OSCC. Betel quid chewing, alcohol, smoking, tumour location and staging showed little effect on lymphocyte subtypes. These results suggest that alterations and activation of NK cells, T and B cells are important and associated with disease status in oral carcinogenesis.

A community-based RCT for oral cancer screening with toluidine blue.

Early detection of oral premalignant lesions (OPMLs) by visual inspection with toluidine blue has not been addressed. We conducted a community-based randomized controlled trial to assess whether using toluidine blue as an adjunctive tool for visual screening had a higher detection rate of OPMLs and could further reduce the incidence of oral cancer. In 2000, in Keelung, we randomly assigned a total of 7975 individuals, aged 15 years or older and with high-risk oral habits, to either the toluidine-blue-screened (TBS) group or the visual screening group. Results showed 5% more oral premalignant lesions and 79% more oral submucous fibrosis detected in the TBS group than in the control group. After a five-year follow-up ascertaining oral cancer development through linkage to the National Cancer Registry, the incidence rate in the TBS group (28.0 x 10(-5)) was non-significantly 21% lower than that in the control group (35.4 x 10(-5)).

Association of androgenetic alopecia with metabolic syndrome in men: a community-based survey.

BACKGROUND: Several previous studies have investigated the association between factors related to metabolic syndrome, which is known to increase the risk of type 2 diabetes mellitus and cardiovascular disease, and androgenetic alopecia (AGA). However, the results of these studies have been inconsistent. OBJECTIVES: To determine if there is an association between metabolic syndrome and AGA after adjustment for potential confounders. METHODS: A population-based cross-sectional survey was conducted in Tainan, Taiwan. A total of 740 subjects aged 40-91 years participated in the survey between April and June 2005. The Norwood classification was used to assess the degree of hair loss. Information on components of metabolic syndrome together with other possible risk factors was collected. RESULTS: A statistically significant association was found between AGA and the presence of metabolic syndrome [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.01-2.74] as well as between AGA and the number of fulfilled metabolic syndrome components (OR 1.21, 95% CI 1.03-1.42) after controlling for age, family history of AGA and smoking status. Among metabolic syndrome components, high-density lipoprotein cholesterol (HDL-C) (OR 2.36, 95% CI 1.41-3.95; P = 0.001) was revealed as the most important factor associated with AGA. CONCLUSIONS: Our population-based study found a significant association between AGA and metabolic syndrome; among the components of metabolic syndrome, HDL-C was found to be of particular importance. This finding may have significant implications for the identification of metabolic syndrome in patients with moderate or severe AGA. Early intervention for metabolic syndrome is critical to reduce the risk and complications of cardiovascular disease and type 2 diabetes mellitus later in life.

Cumulative survival in early-onset unilateral and bilateral breast cancer: an analysis of 1907 Taiwanese women.

As the epidemiological pattern of breast cancer in modernising Asian countries differs greatly from that in Western countries, it is worthwhile to investigate the long-term prognoses of unilateral and bilateral breast cancer in these nations. A retrospective cohort study composed of 1907 Taiwanese women was conducted to follow 1863 unilateral and 44 bilateral cases of breast cancer. Time-dependent Cox regression was used to assess the risk of breast cancer death by considering the time course of unilateral and bilateral tumour development. The 15-year survival rates were 68.37, 62.63, and 26.42% for unilateral, synchronous bilateral, and metachronous bilateral breast cancer, respectively. Differences among types were most apparent after 5 years of follow-up. After adjusting for significant prognostic factors, the risk of death for overall bilateral breast cancer was 2.50-fold greater (95% CI, 1.43-4.37) compared to unilateral breast cancer. The corresponding figures were 1.12-fold (95% CI, 0.42-3.02) and 6.11-fold (95% CI, 3.14-11.89) for synchronous and metachronous bilateral breast cancer, respectively. Taiwanese women, who are frequently diagnosed with breast cancer before 50 years of age, showed poorer survival for metachronous bilateral than for synchronous bilateral or unilateral breast cancer. Survival was markedly poorer compared to recent data from Sweden.

The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease (GORD), which remains elusive, was quantified. METHODS: The population included 3669 subjects undergoing repeated upper endoscopy. Data were analysed using a three-state Markov model to estimate transition rates (according to the Los Angeles classification) regarding the natural course of the disease. Individual risk score together with the kinetic curve was derived by identifying significant factors responsible for the net force between progression and regression. RESULTS: During three consecutive study periods, 12.2, 14.9 and 17.9% of subjects, respectively, progressed from non-erosive to erosive disease, whereas 42.5, 37.3 and 34.6%, respectively, regressed to the non-erosive stage. The annual transition rate from non-erosive to class A-B disease was 0.151 per person year (95% CI 0.136 to 0.165) and from class A-B to C-D was 0.079 per person year (95% CI 0.063 to 0.094). The regression rate from class A-B to non-erosive disease was 0.481 per person year (95% CI 0.425 to 0.536). Class C-D, however, appeared to be an absorbing state when not properly treated. Being male (relative risk (RR) 4.31; 95% CI 3.22 to 5.75), smoking (RR 1.20; 95% CI 1.03 to 1.39) or having metabolic syndrome (RR 1.75; 95% CI 1.29 to 2.38) independently increased the likelihood of progressing from a non-erosive to an erosive stage of disease and/or lowered the likelihood of disease regression. The short-term use of acid suppressants (RR 0.54; 95% CI 0.39 to 0.75) raised the likelihood of regression from erosive to non-erosive disease. CONCLUSIONS: Intraoesophageal damage is a dynamic and migratory process in which the metabolic syndrome is associated with accelerated progression to or attenuated regression from erosive states. These findings have important implications for the design of effective prevention and screening strategies.

The impact of climate on Japanese encephalitis.

The aim of this study was to assess the change of seasonal pattern of Japanese encephalitis (JE) cases in the post-vaccination period and to elucidate whether the lagged climate variables (precipitation and temperature) were associated with occurrence of JE after adjustment for seasonal pattern, time trend, geographic areas, pig density, vaccination coverage rate for humans, and time dependence of time-series numbers of JE cases. A total of 287 confirmed JE cases between 1991 and 2005 were collected, together with monthly data on socio-ecological archival data including climate, pig density and vaccination. A time-series generalized autoregressive Poisson regression model was used to achieve the objectives. The rate of JE increased from 1998 onwards. The seasonal pattern on occurrence of JE cases clustered between May and August during the period from 1991 to 2005 in Taiwan. In each geographic area, monitoring temperature and precipitation, two possible proxy variables for mosquito density, in conjunction with seasonal factors and pig density is of assistance in forecasting JE epidemics.

Bayesian random-effect model for predicting outcome fraught with heterogeneity--an illustration with episodes of 44 patients with intractable epilepsy.

OBJECTIVE: The study aimed to develop a predictive model to deal with data fraught with heterogeneity that cannot be explained by sampling variation or measured covariates. METHODS: The random-effect Poisson regression model was first proposed to deal with over-dispersion for data fraught with heterogeneity after making allowance for measured covariates. Bayesian acyclic graphic model in conjunction with Markov Chain Monte Carlo (MCMC) technique was then applied to estimate the parameters of both relevant covariates and random effect. Predictive distribution was then generated to compare the predicted with the observed for the Bayesian model with and without random effect. Data from repeated measurement of episodes among 44 patients with intractable epilepsy were used as an illustration. RESULTS: The application of Poisson regression without taking heterogeneity into account to epilepsy data yielded a large value of heterogeneity (heterogeneity factor = 17.90, deviance = 1485, degree of freedom (df) = 83). After taking the random effect into account, the value of heterogeneity factor was greatly reduced (heterogeneity factor = 0.52, deviance = 42.5, df = 81). The Pearson chi2 for the comparison between the expected seizure frequencies and the observed ones at two and three months of the model with and without random effect were 34.27 (p = 1.00) and 1799.90 (p < 0.0001), respectively. CONCLUSION: The Bayesian acyclic model using the MCMC method was demonstrated to have great potential for disease prediction while data show over-dispersion attributed either to correlated property or to subject-to-subject variability.

Positional relationships between photoperiod response QTL and photoreceptor and vernalization genes in barley.

Winterhardiness has three primary components: photoperiod (day length) sensitivity, vernalization response, and low temperature tolerance. Photoperiod and vernalization regulate the vegetative to reproductive phase transition, and photoperiod regulates expression of key vernalization genes. Using two barley mapping populations, we mapped six individual photoperiod response QTL and determined their positional relationship to the phytochrome and cryptochrome photoreceptor gene families and the vernalization regulatory genes HvBM5A, ZCCT-H, and HvVRT-2. Of the six photoreceptors mapped in the current study (HvPhyA and HvPhyB to 4HS, HvPhyC to 5HL, HvCry1a and HvCry2 to 6HS, and HvCry1b to 2HL), only HvPhyC coincided with a photoperiod response QTL. We recently mapped the candidate genes for the 5HL VRN-H1 (HvBM5A) and 4HL VRN-H2 (ZCCT-H) loci, and in this study, we mapped HvVRT-2, the barley TaVRT-2 ortholog (a wheat flowering repressor regulated by vernalization and photoperiod) to 7HS. Each of these three vernalization genes is located in chromosome regions determining small photoperiod response QTL effects. HvBM5A and HvPhyC are closely linked on 5HL and therefore are currently both positional candidates for the same photoperiod effect. The coincidence of photoperiod-responsive vernalization genes with photoperiod QTL suggests vernalization genes should also be considered candidates for photoperiod effects.

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 > or = 135 mmHg or DBP > or = 85 mmHg) (adjusted odd ratio: 0.89 (0.83-0.94)) and high triglyceride (> or = 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.

Tuberculin reactivity in adults after 50 years of universal bacille Calmette-Guerin vaccination in Taiwan.

We aimed to assess whether tuberculin reactivity in adults is affected by bacille Calmette-Guerin (BCG) vaccination after 50 years of universal BCG vaccination with 80-95% coverage. A community-based study on tuberculin reactivity in 619 participants was conducted in February 2000 in Keelung city, Taiwan. Information on BCG vaccination policies and annual risk of infection (ARI) in the underlying population was extracted from consecutive national prevalence surveys relating to the period 1952-1997. Compared with the expected ARI estimate, the standardized morbidity ratio of positive tuberculin response for vaccination in infancy was 2.2 (95% CI 0.3-15.5) for those aged <10 years. The corresponding figures for older age groups ranged from 3.6 (95% CI 2.2-5.9) for those aged 10-12 years to 0.7 (95% CI 0.5-0.9) for those aged 57-67 years. This suggests that the effect of BCG vaccination on positive tuberculin response in adults aged >30 years is probably negligible irrespective of age at vaccination or revaccination and that the tuberculin skin test can be used to diagnose TB in control programmes in countries with moderate or high incidence of TB.

A population-based study of the association between areca nut chewing and type 2 diabetes mellitus in men (Keelung Community-based Integrated Screening programme No. 2).

AIMS/HYPOTHESIS: The aim of this study was to assess whether the diabetogenicity of areca nut (Areca catechu or 'betel-nut'), which has previously been demonstrated experimentally in mice, independently contributes to the risk of hyperglycaemia or type 2 diabetes in men in Taiwan, where the habit has become established relatively recently. METHODS: We used data from a population-based cross-sectional survey and a multiple-disease-screening programme that tested for hyperglycaemia, type 2 diabetes and risk factors related to type 2 diabetes. Data on habitual areca nut chewing were available for 14,816 men. Multiple logistic regression models were used to determine whether areca nut chewing was an independent risk factor for type 2 diabetes. RESULTS: Compared with non-chewers, areca nut chewers had higher age-adjusted prevalence rates for hyperglycaemia (11.4% vs 8.7%) and type 2 diabetes (10.3% vs 7.8%). Areca nut chewing independently increased the risk of hyperglycaemia (adjusted odds ratio [OR] 1.19, 95% CI 0.97-1.45) and type 2 diabetes (adjusted OR 1.29, 95% CI 1.04-1.60). The independent effects of duration of chewing were dose-dependent for type 2 diabetes (adjusted OR 1.32 for the duration of 10-19 years and 1.41 for the duration of > or =20 years), as were the effects of increased rates of areca nut chewing (adjusted OR 1.14 for <10 pieces/day, 1.30 for 10-19 pieces/day and 2.02 for > or =20 pieces/day); similar findings were noted for hyperglycaemia. CONCLUSIONS/INTERPRETATION: The habit of chewing areca nut independently contributes to the risk of both hyperglycaemia and type 2 diabetes in Taiwanese men. This association is dose-dependent with respect to the duration of areca nut use and the quantity of areca nut chewed per day.

Impact of betel quid, tobacco and alcohol on three-stage disease natural history of oral leukoplakia and cancer: implication for prevention of oral cancer.

The natural history of the three-stage process from normal, oral leukoplakia to oral cancer in relation to betel quid chewing, smoking and drinking is rarely addressed. The aim of this study was to simultaneously quantify the effects of three risk factors on occurrence of oral leukoplakia and malignant transformation to oral cancer. A hospital-based case-control study design derived from three retrospective cohorts from 1988 to 1998 was conducted. A total of 74 oral cancer patients, 164 patients with oral leukoplakia and 187 controls were interviewed to collect information on their betel chewing, smoking and drinking habits. The effects of the three risk factors on the progression rates of the three-stage disease process were estimated using the three-state Markov model. Subjects who chewed betel quid were at greater risk of leukoplakia (adjusted odds ratio (OR) 17.7 (9.03-34.5)) but there was no significant effect on malignant transformation (OR 1.04 (0.61-1.76)). Smoking played a major role in the onset of leukoplakia (OR 4.26 (2.21-8.23)) but a minor role in malignant transformation (OR 1.36 (0.69-2.68)). Alcohol was positively associated with malignant transformation (OR 2.37 (1.47-3.82)) but unrelated to occurrence of leukoplakia (OR 0.76 (0.04-1.43)). We concluded that smoking and betel quid were two significant risk factors for the occurrence of leukoplakia, whereas alcohol was significantly responsible for malignant transformation.

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. METHODS: We studied a cohort of 795 patients with diabetes mellitus (DM) receiving fundus examination in the ophthalmology out-patient department of one medical centre between 1 January 1990 and 31 December 1992 in Taiwan. Follow-up data until 31 December 1998 were collected by chart review. Two multistate Markov models were proposed to assess the efficacy of the treatment regime in reducing progression to blindness. RESULTS: The average times spent in states (i) no diabetic retinopathy (NDR), (ii) background diabetic retinopathy (BDR), (iii) preproliferative diabetic retinopathy (PPDR), and (iv) proliferative retinopathy (PDR) were 10.86 years, 8.33 years, 1.67 years, and 2.17 years, respectively. Early detection of PPDR may lead to a 60% reduction in PDR and an 83% reduction in blindness. Simulated results based on these parameters show that an annual screening programme, a biennial screening regime and a 4-yearly screening regime can lead to 54% (95% confidence interval (CI): 44-62%), 51% (95% CI: 41-59%), and 46% (95% CI: 36-54%) reductions in blindness, respectively. CONCLUSIONS: Assessing the progression of DR following the proliferative pathway in this study suggests that screening for DR is worthwhile and that a 4-year interscreening interval for patients as yet without DR may be justified.

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.