Eun-Kee Park

Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008

OBJECTIVE To carry out a descriptive analysis of mesothelioma deaths reported worldwide between 1994 and 2008. METHODS We extracted data on mesothelioma deaths reported to the World Health Organization mortality database since 1994, when the disease was first recorded. We also sought information from other English-language sources. Crude and age-adjusted mortality rates were calculated and mortality trends were assessed from the annual percentage change in the age-adjusted mortality rate. FINDINGS In total, 92,253 mesothelioma deaths were reported by 83 countries. Crude and age-adjusted mortality rates were 6.2 and 4.9 per million population, respectively. The age-adjusted mortality rate increased by 5.37% per year and consequently more than doubled during the study period. The mean age at death was 70 years and the male-to-female ratio was 3.6:1. The disease distribution by anatomical site was: pleura, 41.3%; peritoneum, 4.5%; pericardium, 0.3%; and unspecified sites, 43.1%. The geographical distribution of deaths was skewed towards high-income countries: the United States of America reported the highest number, while over 50% of all deaths occurred in Europe. In contrast, less than 12% occurred in middle- and low-income countries. The overall trend in the age-adjusted mortality rate was increasing in Europe and Japan but decreasing in the United States. CONCLUSION The number of mesothelioma deaths reported and the number of countries reporting deaths increased during the study period, probably due to better disease recognition and an increase in incidence. The different time trends observed between countries may be an early indication that the disease burden is slowly shifting towards those that have used asbestos more recently.

Global magnitude of reported and unreported mesothelioma.

Background Little is known about the global magnitude of mesothelioma. In particular, many developing countries, including some with extensive historical use of asbestos, do not report mesothelioma. Objectives We estimated the global magnitude of mesothelioma accounting for reported and unreported cases. Methods For all countries with available data on mesothelioma frequency and asbestos use (n = 56), we calculated the 15-year cumulative number of mesotheliomas during 1994–2008 from data available for fewer years and assessed its relationship with levels of cumulative asbestos use during 1920–1970. We used this relationship to predict the number of unreported mesotheliomas in countries for which no information on mesothelioma is available but which have recorded asbestos use (n = 33). Results Within the group of 56 countries with data on mesothelioma occurrence and asbestos use, the 15-year cumulative number of mesothelioma was approximately 174,300. There was a statistically significant positive linear relation between the log-transformed national cumulative mesothelioma numbers and the log-transformed cumulative asbestos use (adjusted R2 = 0.83, p < 0.0001). Extrapolated to the group of 33 countries without reported mesothelioma, a total of approximately 38,900 (95% confidence interval, 36,700–41,100) mesothelioma cases were estimated to have occurred in the 15-year period (1994–2008). Conclusions We estimate conservatively that, globally, one mesothelioma case has been overlooked for every four to five reported cases. Because our estimation is based on asbestos use until 1970, the many countries that increased asbestos use since then should anticipate a higher disease burden in the immediate decades ahead.

Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study.

RATIONALE Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown. OBJECTIVES We aimed to evaluate SMRP in an asbestos-exposed cohort. METHODS A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography. MEASUREMENTS AND MAIN RESULTS Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01). CONCLUSIONS This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

Asbestos: use, bans and disease burden in Europe

Abstract Objective To analyse national data on asbestos use and related diseases in the European Region of the World Health Organization (WHO). Methods For each of the 53 countries, per capita asbestos use (kg/capita/year) and age-adjusted mortality rates (deaths/million persons/year) due to mesothelioma and asbestosis were calculated using the databases of the United States Geological Survey and WHO, respectively. Countries were further categorized by ban status: early-ban (ban adopted by 2000, n = 17), late-ban (ban adopted 2001–2013, n = 17), and no-ban (n = 19). Findings Between 1920–2012, the highest per capita asbestos use was found in the no-ban group. After 2000, early-ban and late-ban groups reduced their asbestos use levels to less than or equal to 0.1 kg/capita/year, respectively, while the no-ban group maintained a very high use at 2.2 kg/capita/year. Between 1994 and 2010, the European Region registered 106 180 deaths from mesothelioma and asbestosis, accounting for 60% of such deaths worldwide. In the early-ban and late-ban groups, 16/17 and 15/17 countries, respectively, reported mesothelioma data to WHO, while only 6/19 countries in the no-ban group reported such data. The age-adjusted mortality rates for mesothelioma for the early-ban, late-ban and no-ban groups were 9.4, 3.7 and 3.2 deaths/million persons/year, respectively. Asbestosis rates for the groups were 0.8, 0.9 and 1.5 deaths/million persons/year, respectively. Conclusion Within the European Region, the early-ban countries reported most of the current asbestos-related deaths. However, this might shift to the no-ban countries, since the disease burden will likely increase in these countries due the heavy use of asbestos.

Osteopontin levels in an asbestos-exposed population.

Purpose: Serum osteopontin levels in patients with malignant mesothelioma have been reported to be higher than in healthy subjects. This study assessed serum osteopontin levels in an asbestos-exposed population to test whether nonmalignant asbestos-related disorders could influence osteopontin levels. Experimental Design: This cross-sectional study evaluated serum osteopontin levels in 525 male subjects. Subjects were classified into six different diagnostic groups, including asbestosis (n = 23), silicosis (n = 20), diffuse pleural thickening (n = 110), asbestosis and diffuse pleural thickening (n = 13), pleural plaques (n = 142), and healthy subjects with a history of asbestos exposure (n = 217). Results: Mean serum osteopontin levels differed among the six groups (P < 0.0001). Mean osteopontin values of the healthy individuals exposed to asbestos were significantly different from that of subjects with asbestosis (P < 0.001) and diffuse pleural thickening (P < 0.001). There was a significant difference in mean serum levels of osteopontin in healthy individuals exposed to asbestos (n = 217) compared with the group mean of all subjects with asbestos-related disorders (n = 288; P < 0.0001). Conclusions: Our results suggest that osteopontin levels are elevated in subjects with asbestos-related disorders without malignant mesothelioma. These data indicate that osteopontin, although reported to be useful for detecting malignant mesothelioma in asbestos-exposed individuals, may be influenced by nonmalignant processes.

Elimination of asbestos use and asbestos-related diseases: An unfinished story

Asbestos is a proven human carcinogen. Asbestos‐related diseases (ARDs) typically comprise lung cancer, malignant mesothelioma, asbestosis, pleural plaques, thickening and effusion. International organizations, notably the World Health Organization and the International Labour Organization, have repeatedly declared the need to eliminate ARDs, and have called on countries to stop using asbestos. However, the relevant national‐level indicators (e.g., incidence/mortality rates and per capita asbestos use, as well as their interrelationships) indicate that ARDs are increasing and asbestos use is continuing in the world. Lessons learned by industrialized countries in terms of policy and science have led to a growing number of countries adopting bans. In contrast, industrializing countries are faced with a myriad of forces prompting them to continue using asbestos. Full‐scale international cooperation will thus be needed, with industrialized countries sharing their experiences and technologies to enable industrializing countries to make smooth transitions to banned states and achieve the goal of eliminating ARDs.

Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population.

Abstract Background: Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study. Methods: Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations. Results: The mean age [± standard deviation (SD)] of participants was 66.9 (±10.1) years, and mean (±SD) serum SMRP concentration was 0.91 (±0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=–0.1254, p=0.0036), BMI (Pearson r=–0.1594, p=0.0002), blood glucose (Pearson r=–0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=–0.1847, p<0.0001), eGFR (Pearson r=–0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=–0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001). Conclusions: This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP. Clin Chem Lab Med 2010;48:869–74.

Transcriptional characterization of Wnt pathway during sequential hepatic differentiation of human embryonic stem cells and adipose tissue-derived stem cells.

Human embryonic stem cells (hESs) and adipose-derived stem cells (hADSCs) are able to differentiate into hepatocytes. However, a role of Wnt signaling in hepatic differentiation of stem cells is unclear. This study characterized the transcriptional expression pattern of Wnt signaling genes during the sequential hepatocytes differentiation of hES and hADSC. The sequential hepatocytes differentiation of hES and hADSC was induced by three steps including induction, differentiation and maturation steps with the treatment of cytokines. Hepatocytes differentiation was more efficient in hES than hADSC in terms of the expression of hepatocyte-specific genes and the cellular uptake of ICG. The expression of WNT2B, WNT5A, and WISP1 increased at late hepatic differentiation of hES, but the expression of DKK1 and CCND1 decreased during early hepatic differentiation of hES. During hepatic differentiation of hADSC, the expression of WNT2B and WISP1 decreased, but the expression of WNT5B and DKK1 increased at late hepatic differentiation. These results showed that Wnt signaling appears to be activated in hepatic differentiation of hES, but repressed in hepatic differentiation of hADSC in a time-dependent manner, which suggests the differential regulation of Wnt signaling for hepatic differentiation of hES and hADSC.

Potential years of life lost (PYLL) caused by asbestos-related diseases in the world.

BACKGROUND We applied the well-established, but rather under-utilized, indicator of Potential Years of Life Lost (PYLL) to estimate the global burden of mesothelioma and asbestosis. METHODS We analyzed all deaths caused by mesothelioma and asbestosis that were reported by 82 and 55 countries, respectively, to the World Health Organization (WHO) from 1994 to 2010. RESULTS The 128,015 and 13,885 persons who died of mesothelioma and asbestosis, potentially lost a total of 2.18 million and 180,000 years of life (PYLL), or, an annual average PYLL of 201,000 years and 17,000 years, respectively. The average PYLL per decedent were 17.0 and 13.0 years for mesothelioma and asbestosis, respectively. CONCLUSIONS The current burden of asbestos-related diseases (ARDs) in terms of PYLL is substantial. The future burden of ARDs can be eliminated by stopping the use of asbestos.

Clinical features of infectious endophthalmitis in South Korea: a five-year multicenter study.

BackgroundTo investigate clinical features of infectious endophthalmitis over five years in a South Korean population.MethodsMedical records of consecutive patients diagnosed with infectious endophthalmitis at eight institutions located in Gyeongsangnam-do and Pusan city between January 1, 2004 and July 31, 2010 were reviewed.ResultsA total of 197 patients were diagnosed and treated. An average of 30.0 infectious endophthalmitis per year was developed. The annual incidence rate of postoperative endophthalmitis during 2006 ~ 2009 was 0.037%. The ratios of male to female and right to left were 50.2%: 49.8 % and 54.8%: 43.2%, respectively. Eighth decade and spring were the peak age (36.6%) and season (32.0%) to develop the infectious endophthalmitis. The most common past history in systemic disease was hypertension (40.4%), followed by diabetes (23.4%). Cataract operation (60.4%) was the most common cause, among which most of them was uneventful phacoemulsification (95.9%). Corneal laceration (51.6%) and liver abscess (42.9%) were the most common causes of traumatic and endogenous endophthalmitis, respectively. The percentages of patients with initial and final visual acuity less than counting fingers were 62.6% and 35.2%, respectively. Treatment with vitrectomy with or without intravitreal antibiotics injection was administered to 72.6% of patients, while 17.3% received intravitreal antibiotics only.ConclusionsOur study revealed that the development of infectious endophthalmitis was related with seasonal variation and increased during our study period. Pars plana vitrectomy was preferred for the treatment of infectious endophthalmitis in South Korea.