The Effect of Respiratory Motion in Breast Intensity-modulated Radiation Therapy: 3D-Printed Dynamic Phantom Study.

BACKGROUND/AIM: This study evaluated the dosimetric effect of respiratory motion in intensity-modulated radiation therapy (IMRT) for breast cancer using a three-dimensional (3D)-printed dynamic phantom. MATERIALS AND METHODS: Computed tomography (CT) data from breast cancer patients were used to create a 3D-printed breast phantom. Various types of treatment plans were generated using CT images acquired at the exhalation phase. Different infill densities in the 3D-printed phantom were tested to validate their effect on simulating the average human breast tissue density. Plans were delivered to the 3D-printed dynamic phantom in the exhalation position and free-breathing motion. Dosimetric verification was performed using Gafchromic EBT3 films. RESULTS: After changing the infill density to obtain Hounsfield Unit values similar to those of human breast tissue, a realistic patient-specific breast phantom was fabricated using a 3D printer at 80% infill density. The gamma passing rates of the dose distribution delivered in the exhalation phase and free-breathing motion were 92% or more. In addition, the dynamic phantom doses with free-breathing motion were directly compared with the static phantom dose in terms of sagittal dose profiles. Gamma passing rates of >93% and 90% were achieved at 3%/3 mm and 3%/2 mm, respectively. CONCLUSION: Despite a blurred dose distribution, the dose map of the film measurement with respiratory motion could be delivered without significantly increasing the dose heterogeneity of the tumor bed or loss of target coverage. Our findings demonstrate that the impact of respiration on breast IMRT for whole-breast irradiation was not significant, even in the tumor bed.

Dosimetric Impact of Respiratory Motion During Breast Intensity-modulated Radiation Therapy Using Four-dimensional Dose Calculations.

BACKGROUND/AIM: The use of intensity-modulated radiation therapy (IMRT) in the treatment of breast cancer is increasing worldwide. Despite clear benefits concerning normal tissue sparing and dose homogeneity, the effects of breathing motion and setup error during breast IMRT should be considered. This study aimed to assess the dosimetric impact of respiratory motion on breast IMRT using four-dimensional (4D) dose calculations. PATIENTS AND METHODS: Multiple computed tomography datasets acquired in three representative respiratory amplitudes, were retrospectively re-planned. Based on the reference dose distribution (RDD), motion-adjusted dose distributions (MDD) were recalculated. All 4D dose distributions were calculated by the voxel-based accumulation of RDD and MDD using five temporal probabilities. The dosimetric parameters of the 4D plans were compared to those of RDD. RESULTS: The dosimetric parameters of the planning target volume (PTV) were not significantly different between the RDD and 4D plans. Of the parameters of tumor bed (TB) simultaneous-integrated boost (SIB), the mean dose and V95% for the 4D plans were significantly reduced compared to those of RDD, and the percentage difference in the TB V95% ranged from -1.1% to -5.7% (p<0.05). CONCLUSION: The breast IMRT plan was robust against respiratory motion during tidal breathing. However, special considerations should be made when designing the TB SIB.

Associations of urinary sodium levels with overweight and central obesity in a population with a sodium intake.

BACKGROUND: Previous studies have reported an association between dietary sodium intake and overweight/central obesity. However, dietary survey methods were prone to underestimate sodium intake. Therefore, this study investigated the associations of calculated 24-h urinary sodium excretion, an index of dietary sodium intake, with various obesity parameters including body mass index (BMI) and waist circumference (WC) in a population with a relatively high sodium intake. METHODS: A total of 16,250 adults (aged ≥19 years) and 1476 adolescents (aged 10-18 years), with available information on spot urine sodium levels and anthropometric measurements from the Korea National Health and Nutrition Examination Survey (KNHANES) were included in this study. We calculated 24-h urine sodium excretion levels from spot urine sodium levels using the Tanaka formula. RESULTS: In adults, those with high sodium excretion levels (≥ 3200 mg) showed increased odds of overweight and central obesity compared to those with low urinary sodium excretion level (< 2200 mg) (odds ratio [OR] = 2.17, 95% confidence interval [CI] = 1.90-2.49 for overweight; OR = 2.50, 95% CI = 2.13-2.94 for central obesity). These associations were also observed in adolescents (OR = 5.80, 95% CI = 3.17-10.60 for overweight; OR = 4.19, 95% CI = 1.78-9.89 for central obesity). CONCLUSIONS: The present study suggests that reducing salt intake might be important for preventing overweight and central obesity, especially in adolescents. However, because the present study was conducted with cross-sectional study design, further longitudinal studies are warranted to confirm the causal relationship between urinary sodium excretion and overweight/central obesity.

Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations.

BACKGROUND & AIMS: To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. METHODS: Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. RESULTS: Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30-0.69), and COR (95% CI) = 0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. CONCLUSIONS: High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.

The association between somatic and psychological discomfort and health-related quality of life according to the elderly and non-elderly.

PURPOSE: Symptoms and discomfort are common complaints in primary care settings. It has been postulated that the physical symptoms are informative index in estimating Health-related quality of life (HRQOL). Thus, we conducted a community-based cross-sectional study to assess the relationship between somatic and psychological discomfort and HRQOL in elderly and non-elderly people. METHODS: A total of 2467 participants were recruited in 2013 from a population of 17,066 rural residents aged 20 or older. Information on demographic characteristics, somatic and psychological discomfort symptoms, and HRQOL was collected. Two months after the baseline survey, we conducted a repeated survey to assess changes in the discomfort symptoms and HRQOL. We evaluated associations of the discomfort symptoms with HRQOL using multiple linear regression and mixed model. RESULTS: EuroQol-Visual Analogue Scale (EQ-VAS), index of HRQOL, was correlated with fatigue, pain, sleep disturbances, indigestion, and anxiety/depression, after adjusting for covariates. However, the factors most significantly associated with EQ-VAS differed between the elderly and non-elderly. Pain was the most important factor contributing to EQ-VAS in the elderly, whereas depression and anxiety were the predominant factors in the non-elderly. These relationships were replicated in the repeated measurements to assess the change of symptoms and change of EQ-VAS. CONCLUSION: Our study suggests that somatic and psychological discomfort symptoms are associated with HRQOL. The main factors related to HRQOL vary according to age and large prospective studies and clinical trials are needed to clarify the association between specific symptoms and HRQOL according to the age.

Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells.

Despite many studies of the effect of ionizing radiation, biological mechanisms of action might differ greatly depend on dose, dose rate, and cell type. This study was performed to explore the effects of low- and high-dose radiation in human immune cell lines. We examined cell sensitivity after irradiation with 0.05, 0.1, or 2Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1Gy had no effect on cell survival in any tested cell line, with the exception of IM-9 cells, whose viability was transiently increased. However, IM-9 and C1R-sB7 cells were very sensitive to high-dose radiation-induced cell death, whereas Jurkat and JM1 cells showed moderate sensitivity, and THP-1 cells were completely resistant. This radiosensitivity was correlated with basal AKT activation, which is induced by phosphorylation. In radiosensitive IM-9 cells, priming with chronic low-dose irradiation blocked cell death induced by high-dose radiation challenge via inhibition of caspase activation and PARP cleavage. AKT phosphorylation was not altered in IM-9 cells, but ERK phosphorylation was greatly elevated immediately after chronic low-dose irradiation. Taken together, our results suggest that the different responses of normal and tumor cells to low-dose and high-dose radiation depend on AKT activation, which is regulated by protein phosphatase 2 (PP2A). In radiosensitive normal cells lacking basal AKT activity, chronic low-dose radiation increases activation of the ERK pathway, which plays an important role in the adaptive response to radiation, providing a very important insight into understanding the effects of ionizing radiation on health.

Association of Cigarette Prices with the Prevalence of Smoking in Korean University Students: Analysis of Effects of the Tobacco Control Policy.

BACKGROUND: Increased pricing of cigarettes might be one of the most effective approaches for reducing the prevalence of smoking. This study aimed to investigate the effects of increasing cigarette prices through taxation by a tobacco intervention policy on the changes in smoking prevalence in Korean university students. MATERIALS AND METHODS: The participants in this study were 23,047 healthy university students aged 18-29 years from a health examination in 2011-2015. We investigated the adjusted prevalence of daily and occasional smoking before and after increasing cigarette prices through taxation. RESULTS: The prevalence of occasional smoking was significantly decreased in 2015 from 2014 in both male (from 10.7% in 2014 to 5.4%) and female (from 3.6% to 1.1%) students, but the prevalence of daily smoking did not decrease significantly. The frequency of individuals who had attempted smoking cessation during the past year was significantly higher among occasional smokers in male students (90.2%) compared with daily smokers (64.9%). For female students, there were no differences in experience of smoking cessation, willingness for smoking cessation, or E-cigarette experience between daily and occasional smokers. CONCLUSIONS: We found that a policy of increasing cigarette prices through taxation is associated with decreases in the prevalence of occasional smokers, who have relatively lower nicotine dependence compared with individuals who smoke daily. The results of our study suggest that social support and direct intervention for smoking cessation at the community level are needed for university students alongside the pricing policy.

Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: results from the Korean Genome and Epidemiology Study.

AIMS/HYPOTHESIS: To examine the association between soybean products and risk of type 2 diabetes, we measured four isoflavone biological markers--genistein, daidzein, glycitein and equol--in a nested case-control study. METHODS: The study population was composed of 693 cases (316 women and 377 men) and 698 matched controls (317 women and 381 men) within the Korean Genome and Epidemiology Study. The concentrations of isoflavone biomarkers were measured using HPLC-MS/MS on plasma samples that were collected at baseline. A stratified analysis was undertaken to examine the association between plasma isoflavone concentrations and risk of type 2 diabetes according to sex and equol production. Logistic regression models were used to compute ORs and 95% CIs adjusted for confounders. RESULTS: In women, compared with the lowest quartile of plasma concentration of genistein, the highest quartile exhibited a significantly decreased risk of diabetes (OR 0.58, 95% CI 0.35, 0.95). When stratified by equol-producing status in women, the OR for diabetes in the highest vs the lowest quartile of genistein concentration was 0.31 (95% CI 0.16, 0.60) in equol producers, but genistein concentration was not associated with risk of diabetes in equol non-producers (p for interaction = 0.013). In men, isoflavone concentrations were not associated with risk of diabetes, regardless of equol-producing status. CONCLUSIONS/INTERPRETATION: High plasma concentrations of genistein were associated with a decreased risk of type 2 diabetes in women. This inverse association was prominent in equol-producing participants. These results suggest a beneficial effect of a high intake of soybean products on risk of type 2 diabetes in women.

Viral hepatitis and liver cancer in Korea: an epidemiological perspective.

In the past, hepatitis B virus (HBV) infection was endemic in the general Korean population. The association of HBV infection with the occurrence of liver cancer has been well demonstrated in several epidemiologic studies. While the mortality rates of liver cancer in Korea have decreased steadily over the last decade, the presence of hepatitis B surface antigen (HBsAg) in mothers remains high at 3-4%, and 25.5% of these HBsAg positive mothers are positive for hepatitis B e antigen (HBeAg). HBV infection caused almost a quarter of hepatocellular carcinoma (HCC) cases and one-third of deaths from HCC. These aspects of HBV infection prompted the Korean government to create a vaccination program against HBV in the early 1980s. In 1995, the Communicable Disease Prevention Act (CDPA) was reformed, and the government increased the number of HBV vaccines in the National Immunization Program (NIP), driving the vaccination rate up to 95%. In 2000, the National Health Insurance Act (NHIA) was enacted, which provided increased resources for the prevention of perinatal HBV infection. Then in 2002, the Korean government, in conjunction with the Korean Medical Association (KMA), launched an HBV perinatal transmission prevention program. The prevalence of HBsAg in children had been high (4-5%) in the early 1980s, but had dropped to below 1% in 1995, and finally reached 0.2% in 2006 after the NIP had been implemented. After the success of the NIP, Korea finally obtained its first certification of achievement from the Western Pacific Regional Office of the World Health Organization (WPRO-WHO) for reaching its goal for HBV control. An age-period-cohort analysis showed a significant reduction in the liver cancer mortality rate in children and adolescents after the NIP had been implemented. In addition to its vaccination efforts, Korea launched the National Cancer Screening Program (NCSP) for 5 leading sites of cancer, including the liver, in 1999. As a consequence of this program, the 5-year liver cancer survival rate increased from 13.2% (1996-2000) to 23.3% (2003-2008). The development of both the primary and secondary prevention for liver cancer including HBV immunization and cancer screening has been of critical importance.

The monetary value of the man-mSv for Korean NPP radiation workers assessed by the radiation aversion factor.

The monetary value of the man-mSv for operators of Korean nuclear power plants (NPPs) was calculated using a radiation aversion factor based on a survey of NPP workers. Initially, the life expectancy in the population is 79.4 y, the average age of cancer occurrence is 60 y, the average annual wage for an electric worker is 56 000 $ y(-1) and the nominal risk coefficient induced by radiation is 4.2E(-5) mSv were used to evaluate the basic monetary value (α(base)) resulting in 45.6 $ mSv(-1). To investigate the degree of radiation aversion, the subject of the investigation was selected as the working radiation workers in 10 NPPs in Korea (Kori 1-2, Yeonggwang 1-3, Ulchin 1-3 and Wolseong 1-2). In August 2010, with the cooperation of KHNP and partner companies, a total of 2500 survey questionnaires to 10 NPPs (or 250 surveys to each NPP) were distributed to currently employed radiation workers. From these, 2157 responses were obtained between August and October 2010. The assessed radiation aversion factor and the monetary value of the man-mSv from the calculated radiation aversion factor were 1.26 and ∼50 $ in the 0-1 mSv range, 1.38 and ∼200 $ in the 1-5 mSv range, 1.52 and ∼1000 $ in the 5-10 mSv range, 1.65 and ∼4000 $ in the 10-20 mSv range and 1.74 and ∼8500 $ >20 mSv.

Radiation dose distribution for workers in South Korean nuclear power plants.

A total of 33 680 nuclear power plants (NPPs) workers were monitored and recorded from 1990 to 2007. According to the record, the average individual radiation dose has been decreasing continually from 3.20 mSv man(-1) in 1990 to 1.12 mSv man(-1) at the end of 2007. After the International Commission on Radiological Protection 60 recommendation was generalised in South Korea, no NPP workers received >20 mSv radiation, and the numbers of relatively highly exposed workers have been decreasing continuously. The age distribution of radiation workers in NPPs was composed mainly of 20-30 y olds (83 %) for 1990-1994 and 30-40 y olds (75 %) for 2003-2007. The difference in individual average dose by age was not significant. Most (77 %) of the NPP radiation exposures from 1990 to 2007 occurred mostly during the refueling period. With regard to exposure type, the majority of exposures was external exposures, representing 95 % of the total exposures, whereas internal exposures represented only 5 %. External effective dose was affected mainly by gamma radiation exposure, with an insignificant amount of neutron exposure. As for internal effective dose, tritium in the pressurised heavy water reactor was the biggest cause of exposure.

Low-dose of ionizing radiation enhances cell proliferation via transient ERK1/2 and p38 activation in normal human lung fibroblasts.

This study shows the human cellular responses and the mechanism of low-dose ionizing radiation in CCD 18 Lu cells, which are derived from normal human lung fibroblasts. Cell proliferation and viability assay were measured for the cells following gamma-irradiation using trypan blue, BrdU incorporation, and Wst-1 assay. We also examined genotoxicity using a micronuclei formation assay. The activation of the MAPKs pathway was determined by Western blot analysis, and the siRNA system was used to inhibit the expression of ERK1/2 and p38. We found that 0.05 Gy of ionizing radiation stimulated cell proliferation and did not change Micronuclei frequencies. In addition, 0.05 Gy of ionizing radiation activated ERK1/2 and p38, but did not activate JNK1/2 in cells. A specific ERK1/2 inhibitor, U0126, decreased the phosphorylation of ERK1/2 proteins induced by 0.05 Gy of ionizing radiation, and a similar suppressive effect was observed with a p38 inhibitor, PD169316. Suppression of ERK1/2 and p38 phosphorylation with these inhibitors decreased cell proliferation, which was stimulated by 0.05 Gy of ionizing radiation. Furthermore, downregulation of ERK1/2 and p38 expression using siRNA blocked the cell proliferation that had been increased by 0.05 Gy of ionizing radiation. These results suggest that 0.05 Gy of ionizing radiation enhances cell proliferation through the activation of ERK1/2 and p38 in normal human lung fibroblasts.