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1.  Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer 
Purpose
Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients.
Materials and Methods
This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model.
Results
Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m2 (range, 85 to 1,583 mg/m2). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ≥55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN.
Conclusion
We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.
doi:10.4143/crt.2010.42.4.185
PMCID: PMC3021736  PMID: 21253319
Colorectal neoplasms; Oxaliplatin; Neurotoxicity
2.  Time to establish multidisciplinary childhood cancer survivorship programs in Korea 
Improved treatment strategies and better supportive care have resulted in increased survival rates for childhood cancers. However, most of the survivors may have complex, long-term health issues. In 2004, Childhood Cancer Survivorship Study of the United States confirmed that both survivors and the medical community need to be educated about the late effects of childhood cancer treatment. Korea, with an estimated number of childhood cancer survivors of 20,000 to 25,000, faces similar challenges that the United States had experienced earlier. Despite of the tight budgetary situation on the part of government and hospitals, nationwide cohort study for Korean childhood cancer survivors was proposed and the versions of instruments to measure the quality of life of childhood cancer survivors were already validated. Nationwide registry of long-term survivors as well as the multi-center study is to be developed not only for the care of the survivors but also to raise the patient's awareness of the importance of regular follow-up. In addition to education of primary care providers regarding the survivorship, the need for special education program in the school system is emphasized.
doi:10.5045/kjh.2010.45.2.84
PMCID: PMC2983029  PMID: 21120183
3.  Neurocognitive functioning and health-related behaviors in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study 
SUMMARY
Background
Positive health-related behaviors are essential for the future wellbeing of childhood cancer survivors, though relatively few maintain healthy behaviors into adulthood.
Methods
Neurocognitive function and emotional distress were examined in 6,440 adult survivors from the Childhood Cancer Survivor Study, and used to predict rates of expected health-related behaviors. Covariates included cancer diagnosis, age, sex, body mass index, insurance status, income, and antidepressant medication use, and multivariable models were constructed adjusting for these factors.
Findings
In multivariable regression models, survivors with neurocognitive problems in task efficiency (RR=0.77, 95% CI=0.72–0.84) were less likely to meet the Centers for Disease Control guidelines for weekly physical activity. Survivors with neurocognitive impairment were more likely to engage in general survivor care (RR=1.20, 95% CI=1.10–1.30), and less likely to engage in dental care (RR=0.92, 95% CI=0.88–0.97). Obese survivors were less likely to report receiving a bone density exam (RR=0.67, 95% CI=0.54–0.82), a mammogram (RR=0.71, 95% CI=0.57–0.89), and a skin exam (RR=0.78, 95% CI = 0.68–0.89). Survivors reporting somatization, i.e. vague physical symptoms associated with anxiety, were more likely to report receiving echocardiograms (RR=1.53, 95% CI = 1.32–1.77).
Interpretation
These results support the link between neurocognitive and emotional problems and health-related behaviors in adult survivors of childhood cancer. Monitoring neurocognitive and emotional outcomes may help to identify survivors at risk for poor adherence to prescribed health behaviors and health screening exams.
doi:10.1016/j.ejca.2011.03.001
PMCID: PMC3103640  PMID: 21458986
4.  Relation between Obesity and Bone Mineral Density and Vertebral Fractures in Korean Postmenopausal Women 
Yonsei Medical Journal  2010;51(6):857-863.
Purpose
The traditional belief that obesity is protective against osteoporosis has been questioned. Recent epidemiologic studies show that body fat itself may be a risk factor for osteoporosis and bone fractures. Accumulating evidence suggests that metabolic syndrome and the individual components of metabolic syndrome such as hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are also risk factors for low bone mineral density. Using a cross sectional study design, we evaluated the associations between obesity or metabolic syndrome and bone mineral density (BMD) or vertebral fracture.
Materials and Methods
A total of 907 postmenopausal healthy female subjects, aged 60-79 years, were recruited from woman hospitals in Seoul, South Korea. BMD, vetebral fracture, bone markers, and body composition including body weight, body mass index (BMI), percentage body fat, and waist circumference were measured.
Results
After adjusting for age, smoking status, alcohol consumption, total calcium intake, and total energy intake, waist circumference was negatively related to BMD of all sites (lumbar BMD p = 0.037, all sites of femur BMD p < 0.001) whereas body weight was still positively related to BMD of all sites (p < 0.001). Percentage body fat and waist circumference were much higher in the fracture group than the non-fracture group (p = 0.0383, 0.082 respectively). Serum glucose levels were postively correlated to lumbar BMD (p = 0.016), femoral neck BMD (p = 0.0335), and femoral trochanter BMD (p = 0.0082). Serum high density lipoprotein cholesterol (HDLC) was positively related to femoral trochanter BMD (p = 0.0366) and was lower in the control group than the fracture group (p = 0.011).
Conclusion
In contrast to the effect favorable body weight on bone mineral density, high percentage body fat and waist circumference are related to low BMD and a vertebral fracture. Some components of metabolic syndrome were related to BMD and a vertebral fracture.
doi:10.3349/ymj.2010.51.6.857
PMCID: PMC2995981  PMID: 20879051
Obesity; metabolic syndrome; bone mineral density; vertebral fracture
5.  Evaluation of changes in random blood glucose and body mass index during and after completion of chemotherapy in children with acute lymphoblastic leukemia 
Korean Journal of Pediatrics  2012;55(4):121-127.
Purpose
Improved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment.
Methods
Patients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups.
Results
For random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts.
Conclusion
For a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity.
doi:10.3345/kjp.2012.55.4.121
PMCID: PMC3346834  PMID: 22574072
Acute lymphoblastic leukemia; Random glucose; Body mass index; Child
6.  Obesity Is Underestimated Using Body Mass Index and Waist-Hip Ratio in Long-Term Adult Survivors of Childhood Cancer 
PLoS ONE  2012;7(8):e43269.
Objective
Obesity, represented by high body mass index (BMI), is a major complication after treatment for childhood cancer. However, it has been shown that high total fat percentage and low lean body mass are more reliable predictors of cardiovascular morbidity. In this study longitudinal changes of BMI and body composition, as well as the value of BMI and waist-hip ratio representing obesity, were evaluated in adult childhood cancer survivors.
Methods
Data from 410 survivors who had visited the late effects clinic twice were analyzed. Median follow-up time was 16 years (interquartile range 11–21) and time between visits was 3.2 years (2.9–3.6). BMI was measured and body composition was assessed by dual X-ray absorptiometry (DXA, Lunar Prodigy; available twice in 182 survivors). Data were compared with healthy Dutch references and calculated as standard deviation scores (SDS). BMI, waist-hip ratio and total fat percentage were evaluated cross-sectionally in 422 survivors, in who at least one DXA scan was assessed.
Results
BMI was significantly higher in women, without significant change over time. In men BMI changed significantly with time (ΔSDS = 0.19, P<0.001). Percentage fat was significantly higher than references in all survivors, with the highest SDS after cranial radiotherapy (CRT) (mean SDS 1.73 in men, 1.48 in women, P<0.001). Only in men, increase in total fat percentage was significantly higher than references (ΔSDS = 0.22, P<0.001). Using total fat percentage as the gold standard, 65% of female and 42% of male survivors were misclassified as non-obese using BMI. Misclassification of obesity using waist-hip ratio was 40% in women and 24% in men.
Conclusions
Sixteen years after treatment for childhood cancer, the increase in BMI and total fat percentage was significantly greater than expected, especially after CRT. This is important as we could show that obesity was grossly underestimated using BMI and waist-hip ratio.
doi:10.1371/journal.pone.0043269
PMCID: PMC3419210  PMID: 22905245
7.  Cardiovascular Risk Factors in Adult Survivors of Pediatric Cancer – a report from the Childhood Cancer Survivor Study 
Background
Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular (CV) disease compared with the general population.
Methods
8,599 survivors (52% male) and 2,936 siblings (46% male).from the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained – prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970–1986 were evaluated for BMI ≥30 kg/m2 based on self reported heights and weights and self-reported use of medications for hypertension, dyslipidemia, and impaired glucose metabolism. The presence of ≥3 of the above constituted Cardiovascular Risk Factor Cluster (CVRFC) a surrogate for Metabolic Syndrome
Results
Survivors were more likely than siblings to take medications for hypertension (OR 1.9 95% CI 1.6–2.2), dyslipidemia (OR 1.6 95% CI 1.3–2.0) or diabetes (OR 1.7 95% CI 1.2–2.3). Among these young adults (mean age 32 years for survivors and 33 years for siblings) survivors were not more likely than siblings to be obese or have CVRFC. In a multivariable logistic regression analysis, factors associated with having CVRFC included: older age at interview (≥ 40 vs. < 30 years of age [OR 8.2 95% CI 3.5–19.9]), exposure to total body irradiation (OR 5.5 95% CI 1.5–15.8) or radiation to the chest and abdomen (OR 2.3 95% CI 1.2–2.4), and physical inactivity (OR 1.7 95% CI 1.1–2.6).
Conclusions
Among adult survivors of pediatric cancer, older attained age, exposure to TBI or abdominal plus chest radiation, and a sedentary lifestyle are associated with CVRFC.
doi:10.1158/1055-9965.EPI-09-0555
PMCID: PMC2805162  PMID: 20056636
survivor; cardiovascular risk factors; metabolic syndrome
8.  Continuous renal replacement therapy in neonates weighing less than 3 kg 
Korean Journal of Pediatrics  2012;55(8):286-292.
Purpose
Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for supporting critically ill pediatric patients. However, a few studies present have reported CRRT use and outcome in neonates weighing less than 3 kg. The aim of this study is to describe the clinical application, outcome, and complications of CRRT in small neonates.
Methods
A retrospective review was performed in 8 neonatal patients who underwent at least 24 hours of pumped venovenous CRRT at the Samsung Medical Center in Seoul, Korea, between March 2007 and July 2010. Data, including demographic characteristics, diagnosis, vital signs, medications, laboratory, and CRRT parameters were recorded.
Results
The data of 8 patients were analyzed. At the initiation of CRRT, the median age was 5 days (corrected age, 38+2 weeks to 23 days), and the median body weight was 2.73 kg (range, 2.60 to 2.98 kg). Sixty-two patient-days of therapy were reviewed; the median time for CRRT in each patient was 7.8 days (range, 1 to 37 days). Adverse events included electrolyte disturbances, catheter-related complications, and CRRT-related hypotension. The mean circuit functional survival was 13.9±8.6 hours. Overall, 4 patients (50%) survived; the other 4 patients, who developed multiorgan dysfunction syndrome, died.
Conclusion
The complications of CRRT in newborns are relatively high. However, the results of this study suggest that venovenous CRRT is feasible and effective in neonates weighing less than 3 kg under elaborate supportive care. Furthermore, for using potential benefit of CRRT in neonates, efforts are required for prolonging filter survival.
doi:10.3345/kjp.2012.55.8.286
PMCID: PMC3433565  PMID: 22977441
Critical illness; Infant; Renal replacement therapy; Treatment outcome
9.  Analysis of Prognostic Factors and Treatment Modality Changes in Breast Cancer: A Single Institution Study in Korea 
Yonsei Medical Journal  2007;48(3):465-473.
Purpose
To determine the effects of new breast cancer treatments and to provide a baseline for monitoring the development of breast cancer in Korean women, we conducted an analysis at our institution to determine long-term clinicopathological features, survival rates, and prognostic factors.
Materials and Methods
This study retrospectively analyzed 2,403 patients between Sep 1994 and Dec 2002, who underwent breast cancer surgery at Samsung Medical Center in Korea. Demographic data, pathologic records and surgical records were collected.
Results
After a median follow-up duration of 121.9 (range: 2-158.1) months, the 5-year disease free survival (DFS) was 82.8% and the 10-year DFS was 74.7%. The 5-year and 10-year overall survival (OS) rates were 89.4% and 82.9%, respectively. Using multivariate analyses, we determined that the nodal status (p < 0.001), angioinvasion (p < 0.001), positive PR (p < 0.001), and C-erb-B2 (p < 0.001) were independent prognostic factors for OS. The frequency of breast conserving surgery was 33.9% before Dec 1999, and increased up to 44.1% by year Dec 2002.
Conclusion
Most of the prognostic variables and clinical characteristics of the Korean breast cancer patients were similar to those reported for Western populations. However, the age distribution in Korean patients seemed to be different from that in patients from Western countries.
doi:10.3349/ymj.2007.48.3.465
PMCID: PMC2628104  PMID: 17594155
Breast cancer; survival; disease free survival; breast conserving surgery
10.  Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation 
Survivors of childhood acute lymphoblastic leukemia (ALL) may face an increased risk of metabolic and cardiovascular late effects. In order to determine the prevalence of and risk factors for adverse cardiometabolic traits in a contemporary cohort of pediatric ALL survivors, we recruited 48 off-therapy patients in remission treated with conventional chemotherapy and 26 treated with total body irradiation (TBI) based hematopoietic cell transplantation (HCT) in this cross-sectional pilot study. At a median age of 15 (range 8–21 years), HCT survivors were significantly more likely than non-HCT survivors to manifest multiple cardiometabolic traits including central adiposity, hypertension, insulin resistance, and dyslipidemia. Overall, 23.1% of HCT survivors met criteria for metabolic syndrome (≥3 traits) compared with 4.2% of non-HCT survivors (p=0.02). HCT survivors also had increased C-reactive protein and leptin levels and decreased adiponectin, suggestive of underlying inflammation and increased visceral fat. In multivariate analyses, history of HCT remained associated with ≥2 (OR 5.13, 95% CI 1.54, 17.15) as well as ≥3 (OR 16.72, 95% CI 1.66, 168.80) traits. Other risk factors included any cranial radiation exposure and family history of cardiometabolic disease. In summary, pediatric ALL survivors exposed to TBI-based HCT as well as any cranial radiation may manifest cardiometabolic traits at an early age and should be screened accordingly.
doi:10.1016/j.bbmt.2010.05.016
PMCID: PMC2975816  PMID: 20685399
acute lymphoblastic leukemia; hematopoietic cell transplantation; metabolic syndrome; radiotherapy; survivor
11.  Health Behaviors and Weight Status of Childhood Cancer Survivors and Their Parents: Similarities and Opportunities for Joint Interventions 
Childhood cancer survivors are at increased risk for chronic health conditions that may be influenced by their cancer treatment and unhealthy lifestyle behaviors. Despite the possibility that interventions targeting the survivor-parent dyad may hold promise for this population, a clearer understanding of the role of family factors and the lifestyle behaviors of both survivors and parents is needed. A mailed cross-sectional survey was conducted in 2009 to assess weight status (body mass index), lifestyle behaviors (e.g., diet, physical activity), and the quality of the parent-child relationship among 170 childhood cancer survivors who were treated at M. D. Anderson Cancer Center and 114 of their parents (80% mothers). Survivors were more physically active and consumed more fruits and vegetables than their parents. However, fewer than half of survivors or parents met national guidelines for diet and physical activity, and their weight status and fat intakes were moderately correlated (r=.30–.57, p<.001). Multilevel models showed that, compared with survivors with better-than-average relationships, those with poorer-than-average relationships with their parents were significantly more likely to consume high-fat diets (p<.05). Survivors and their parents may thus benefit from interventions that address common lifestyle behaviors, as well as issues in the family environment that may contribute to an unhealthy lifestyle.
doi:10.1016/j.jada.2011.09.004
PMCID: PMC3225896  PMID: 22117669
childhood cancer; parent-child relationship; diet; physical activity
12.  Growth Effects of Methylphenidate Among Childhood Cancer Survivors: A 12-Month Case-Matched Open-Label Study 
Pediatric blood & cancer  2009;52(1):39-43.
Background
To investigate the effect of stimulant medication [methylphenidate (MPH)] on growth patterns among survivors of childhood cancer (acute lymphoblastic leukemia or brain tumor).
Procedure
Using a case-matched comparison design, childhood cancer survivors participating in a 12-month open-label MPH trial (n = 51) were compared with childhood cancer survivors not taking MPH (n = 51). Measures of body mass index (BMI), height, and weight were obtained at hospital visits and corrected for gender and age using Centers for Disease Control normative data.
Results
Significant deceleration of BMI and weight, but not height, was observed during the 12-month MPH trial for those children taking MPH.
Conclusions
Childhood cancer survivors taking MPH experience significant, though modest, deceleration of BMI and weight across the first year of MPH intervention. The absence of height deceleration, and the presence of only modest BMI and weight deceleration, suggests that MPH is reasonably well tolerated by childhood cancer survivors with respect to growth. Such findings are encouraging in light of increasing evidence that MPH mitigates some of the cognitive late-effects of cancer treatments. Nevertheless, on a case-by-case basis, clinicians should balance the intended benefits of MPH with potential growth effects in this vulnerable population.
doi:10.1002/pbc.21770
PMCID: PMC2585147  PMID: 18855893
leukemia; brain tumor; methylphenidate; growth
13.  Diabetes Mellitus in Long-Term Survivors of Childhood Cancer: Increased Risk Associated with Radiation Therapy A Report for the Childhood Cancer Survivor Study (CCSS) 
Archives of internal medicine  2009;169(15):1381-1388.
Background
Childhood cancer survivors are at increased risk of morbidity and mortality. To further characterize this risk, this study aimed to compare the prevalence of diabetes mellitus (DM) in childhood cancer survivors and their siblings.
Methods
Participants included 8599 survivors in the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained North American cohort of long-term survivors who were diagnosed 1970–1986, and 2936 randomly selected siblings of CCSS survivors. The main outcome was self-reported DM.
Results
Survivors and siblings had mean ages of 31.5 years (range, 17.0–54.1) and 33.4 years (range, 9.6–58.4), respectively. DM was reported in 2.5% of survivors and 1.7% of siblings. Adjusting for body mass index (BMI), age, sex, race/ethnicity, household income, and insurance, survivors were 1.8 times more likely to report DM (95% confidence interval [CI], 1.3–2.5; P<0.001) than siblings, with survivors who received total body irradiation (odds ratio [OR], 12.6; 95% CI, 6.2–25.3; P<0.001), abdominal irradiation (OR, 3.4; 95% CI, 2.3–5.0; P<0.001) and cranial irradiation (OR, 1.6; 95% CI 1.0–2.3; P=0.03) at increased risk. In adjusted models, increased risk of DM was associated with: total body irradiation (OR 7.2; 95% CI, 3.4–15.0; P<0.001); abdominal irradiation (OR 2.7; 95% CI, 1.9–3.8; P<0.001); alkylating agents (OR 1.7; 95% CI, 1.2–2.3; P<0.01); and younger age at diagnosis (0–4 years; OR 2.4; 95% CI 1.3–4.6; P<0.01).
Conclusions
Childhood cancer survivors treated with total body or abdominal irradiation have an increased risk of diabetes that appears unrelated to BMI or physical inactivity.
doi:10.1001/archinternmed.2009.209
PMCID: PMC3529471  PMID: 19667301
Childhood cancer survivor; diabetes mellitus; abdominal radiation; total body irradiation
14.  Medical Care in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2008;26(27):4401-4409.
Purpose
To evaluate whether childhood cancer survivors receive regular medical care focused on the specific morbidities that can arise from their therapy.
Patients and Methods
We conducted a cross-sectional survey of health care use in 8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional cohort of childhood cancer survivors. We assessed medical visits in the preceding 2 years, whether these visits were related to the prior cancer, whether survivors received advice about how to reduce their long-term risks, and whether screening tests were discussed or ordered. Completion of echocardiograms and mammograms were assessed in patients at high risk for cardiomyopathy or breast cancer. We examined the relationship between demographics, treatment, health status, chronic medical conditions, and health care use.
Results
Median age at cancer diagnosis was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range, 17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of medical care, only 31.5% reported care that focused on their prior cancer (survivor-focused care), and 17.8% reported survivor-focused care that included advice about risk reduction or discussion or ordering of screening tests. Among survivors who received medical care, those who were black, older at interview, or uninsured were less likely to have received risk-based, survivor-focused care. Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%) of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or mammogram, respectively.
Conclusion
Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care.
doi:10.1200/JCO.2008.16.9607
PMCID: PMC2653112  PMID: 18802152
15.  Screening and surveillance for second malignant neoplasms in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) 
Annals of internal medicine  2010;153(7):442-451.
Background
Childhood cancer survivors may develop a second malignant neoplasm during adulthood and therefore require regular surveillance.
Objective
To examine adherence to population cancer screening guidelines by survivors at average risk of developing a second malignant neoplasm, and to cancer surveillance guidelines by survivors at high risk of developing a second malignant neoplasm.
Design
Retrospective cohort study.
Setting
The Childhood Cancer Survivor Study (CCSS), a 26 center study of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986.
Patients
4,329 male and 4,018 female survivors of childhood cancer who completed a CCSS questionnaire assessing screening and surveillance for new cancers.
Measurements
Patient-reported receipt and timing of mammography, Papanicolaou smear, colonoscopy, or skin examination was categorized as adherent to the United States Preventive Services Task Force guidelines for survivors at average risk for breast or cervical cancer, or the Children’s Oncology Group guidelines for survivors at high risk for developing breast, colorectal or skin cancer as a result of their therapy.
Results
Among average risk female survivors, 2,743/3,392 (80.9%) reported a Papanicolaou smear within the recommended period, and 140/209 (67.0%) reported a mammogram within the recommended period. Among high risk survivors, rates of recommended mammography among females, and colonoscopy and complete skin exams among both genders were only 241/522 (46.2%), 91/794 (11.5%) and 1,290/4,850 (26.6%), respectively.
Limitations
Data were self report. CCSS participants are a select group of survivors and their compliance may not be representative of all childhood cancer survivors.
Conclusions
Female survivors at average risk for developing a second malignant neoplasm demonstrate reasonable rates of screening for cervical and breast cancer. However, surveillance for new cancers is very poor amongst survivors at highest risk for colon, breast or skin cancer, suggesting that survivors and their physicians need education about their risks and the recommended surveillance.
doi:10.1059/0003-4819-153-7-201010050-00007
PMCID: PMC3084018  PMID: 20921543
16.  Assessment of Selection Bias in Clinic-Based Populations of Childhood Cancer Survivors 
Pediatric blood & cancer  2009;52(3):379-386.
Background
It is not known to what extent prevalence estimates of late effects among childhood cancer survivors derived from clinic based samples represent the actual estimates that would be derived if the entire population of childhood cancer survivors was recruited and evaluated for a particular outcome.
Procedure
In a large retrospective cohort study of childhood cancer survivors, the Childhood Cancer Survivor Study (CCSS), the prevalence of chronic health conditions among participants who reported being seen in a cancer center or long-term follow-up clinic was compared to the prevalence of chronic conditions in the entire cohort.
Results
When compared to survivors who had no medical care in the previous two years, survivors accessing medical follow-up were significantly more likely to have chronic health conditions. Relative risks of reporting a chronic health condition were 1.4 (95% CI 1.3 – 1.5) if seen in a cancer center or long-term follow-up clinic and 1.2 (95% CI 1.1-1.3) if seen in a general medical care setting. Estimates derived from only those childhood cancer survivors who were seen in a cancer center or long term follow-up clinic overestimate the prevalence of any chronic disease by 9.3% (95% CI: 7.0-11.6%).
Conclusions
Applying chronic condition prevalence estimates from a clinical population to the general population of childhood cancer survivors must be undertaken with caution. Survivorship research must maintain a high level of scientific rigor to ensure that results reported in the literature are interpreted within the appropriate context.
doi:10.1002/pbc.21829
PMCID: PMC2628420  PMID: 18989878
17.  A nationwide seroprevalence of total antibody to hepatitis A virus from 2005 to 2009: age and area-adjusted prevalence rates 
Background/Aims
Recent outbreak of hepatitis A in Korea is clearly related to the epidemiological shift of hepatitis A virus (HAV). However, nationwide seroprevalence data have been limited. This study estimated the nationwide, age- and area-adjusted anti-HAV prevalence from 2005 to 2009.
Methods
Retrospective analysis of the results of total anti-HAV test in 25,140 cases which were requested by 1,699 medical institutions throughout the nation to Seoul Clinical Laboratory from Jan. 1 2005 to Dec. 31 2009 was performed. The estimated seroprevalence was adjusted by area and age of the standard population based on the 2005 Census data from Korea National Statistical Office.
Results
The area-adjusted anti-HAV prevalence in the children younger than 10 years were 33.4% in 2005 and 69.9% in 2009. The most susceptible age groups to HAV infection during the last 5 years were teenagers and the young adults in their age of twenties. The area-adjusted seroprevalence in 2009 were 11.9% in the age group of 20-29 years, 23.4% in the age group of 10-19 years, 48.4% in the age group of 30-39 years. The population in 40-49 years showed geographically different seroprevalence with the lowest rate in Seoul (80%).
Conclusions
The most susceptible age group to HAV infection is 10-29 years, while the young children less than 10 years showed about 70% seropositivity. The changing seroepidemiology should be monitored continuously for the proper vaccination and patient care.
doi:10.3350/kjhep.2011.17.1.44
PMCID: PMC3304627  PMID: 21494077
Hepatitis A virus; Hepatitis A antibodies; Epidemiology; Prevalence; Korea
18.  Korean Type 2 Diabetes Patients have Multiple Adenomatous Polyps Compared to Non-diabetic Controls 
Journal of Korean Medical Science  2011;26(9):1196-1200.
We tested the correlation between diabetes and aggressiveness of colorectal polyps in diabetic patients and matched non-diabetic controls. We retrospectively studied 3,505 type 2 diabetes (T2DM) patients without gastrointestinal symptoms who underwent colonoscopy for colorectal cancer at Samsung Medical Center, Seoul, Korea from August 1995 to August 2009. We matched 495 non-diabetic subjects with colon polyps to the diabetic patients in whom polyps were detected by year of colonoscopy, age, sex and body mass index (BMI). Among the 3,505 T2DM patients screened, 509 were found to have 1,136 colon polyps. Those with diabetes had a greater proportion of adenomatous polyps (62.8% vs 53.6%) compared to the control. Multivariate logistic regression analysis identified DM, male gender, age and BMI as independent risk factors for multiple polyps (more than three polyps). Polyp multiplicity in diabetic patients was significantly associated with male gender (OR 2.360, P = 0.005), age (OR 1.033, P = 0.005) and BMI (OR 1.077, P = 0.028). Neither aspirin nor metformin use affected either size or number of polyps in diabetic patients. Male patients older than 65 yr with T2DM and BMI greater than 25 have increased risk for multiple adenomatous polyps and should be screened with colonoscopy to prevent colorectal cancer.
doi:10.3346/jkms.2011.26.9.1196
PMCID: PMC3172658  PMID: 21935276
Diabetes Mellitus; Colonic Polyps; Colorectal Neoplasms
19.  Diet and Physical Activity in Childhood Cancer Survivors: A Review of the Literature 
Treatment advances have led to a growing population of childhood cancer survivors. Many are at risk for developing treatment-related late effects. Diet and physical activity may affect levels of health risk. A number of papers have examined these behaviors in childhood cancer survivors. The purpose of this study was to provide a review and summary of the published studies in the areas of diet, physical activity, and related interventions among childhood cancer survivors. A systematic search was conducted for studies published prior to October 2009. Descriptive and intervention studies that included survivors of childhood cancers and a measurement of diet and/or physical activity were reviewed. Twenty-six manuscripts met criteria: ten addressed diet; 20 addressed physical activity, and six included intervention studies. Results suggest that childhood cancer survivors engage in health-promoting activities at rates comparable to the general population. Behavioral interventions have mostly targeted physical activity. Results, overall, are not encouraging, due primarily to difficulties recruiting and retaining participants. Although more rigorous studies are needed, recommendations for health-promoting behaviors should be a regular topic of discussion between health care providers and their childhood cancer survivor patients.
doi:10.1007/s12160-010-9192-6
PMCID: PMC2935148  PMID: 20559768
Diet; Physical activity; Childhood cancer; Survivors
20.  Clinical evaluation of Dyslipidemia among type II diabetic patients at Public hospital Penang, Malaysia 
Background
Global views emphasize the need for early; effective intervention against the atherogenic dyslipidemia associated with type 2 diabetes and metabolic syndrome to reduce the risk of premature cardiovascular diseases. Our aim was to determine the clinical practices and compliance among dyslipidemia with type II diabetes and hypertension in multiracial society.
Method(s)
Study was carried out in out-patient department of General hospital Penang over a period of ten months (Jan - Oct 2008). Study reflects the retrospective data collection covering a period of three years from Jan 2005 - Dec 2007. Universal sampling technique was used to select all the patients' undergone treatment for diabetes type II and dyslipidemia. All the concerned approvals were obtained from Clinical research Committee (CRC). Data was analyzed by using SPSS 15®.
Result(s)
A total of 501 diabetes type 2 patients with dyslipidemia were identified in this study. The demographic data showed that 55.9% (n = 280) were female patients and 44.1% (n = 221) were males. Patients on combination therapy of metformin with other antidiabetic agent were 79%, while 21% were on monotherapy. Lovastatin was received as monotherapy in 83% of study population, while only 17% were on combination with gemfibrozil. Means of FPG and lipid profile were reduced from the initial (2005) to the latest level (2007) significantly (p < 0.001). Only 0.89% decrease in mean weight with S.D 13.1 as compared to initial S.D 12.8 after three years of Cohort. While in description 35.2% representatives gain weight with majority of males (71.5%), 52.3% with weight loss of 1-3 pounds majority (69.3%) with female respondents and rest 12.4% remains with same weight with mix gender distribution.
Conclusion
Metformin and lovastatin use among patients of type 2 diabetes and dyslipidemia is significantly improved the clinical outcomes. No significant association of metformin or lovastatin is found against the hypertension. Metformin and calcium channel blocker combination therapy was found to be the best choice in the co-treatment of diabetes and hypertension.
doi:10.1186/1755-7682-3-34
PMCID: PMC3002890  PMID: 21092333
21.  Relationship between cardiopulmonary response to exercise and adiposity in survivors of childhood malignancy 
Archives of Disease in Childhood  1997;76(4):298-303.
Accepted 8 November 1996

Many long term sequelae result from previous treatment for malignancy in childhood. However, little information exists on cardiopulmonary response and energy expenditure during exercise and their possible associations with excess body fat. Measurements of body composition and exercise capacity both at low intensity and maximal aerobic capacity were made on 56 long term survivors of childhood malignancy (35 survivors of acute lymphoblastic leukaemia (ALL) and 21 survivors of other malignancies) and 32 siblings acting as controls. Female survivors of ALL had significantly greater mean (SD) body fat than survivors of other malignancies and siblings (32.5 (6.4)% v 24.3 (4.4)% and 26.3 (8.5)% respectively, p<0.005). Energy expenditure at low intensity exercise was reduced in survivors of ALL, and negatively correlated with body fat after controlling for weight (partial r range −0.21 to −0.47, p<0.05). Stroke volume, measured indirectly, was reduced and heart rate raised in ALL survivors at submaximal exercise levels. Peak oxygen consumption was significantly reduced in girls and boys treated for ALL compared with siblings (30.5 v 41.3 ml/kg/min for girls, p<0.05 and 39.9 v 47.6 ml/kg/min for boys, p<0.05 respectively). Reduced exercise capacity may account in part for the excess adiposity observed in long term survivors of ALL.


PMCID: PMC1717158  PMID: 9166019
22.  The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran 
BACKGROUND:
To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.
METHODS:
During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR).
RESULTS:
The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003).
CONCLUSIONS:
The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.
PMCID: PMC3129086  PMID: 21772869
Acute lymphoblastic leukemia; metabolic syndrome; obesity; children
23.  Anal Canal Carcinoma: Experience from a Single Korean Institution 
Yonsei Medical Journal  2007;48(5):827-832.
Purpose
The clinical features, treatment modality approaches in clinical practice, and prognostic factors for anal canal carcinoma patients were retrospectively analyzed.
Materials and Methods
Between October 1994 and December 2005, 50 patients with anal canal cancer were treated at Samsung Medical Center, Seoul, Korea.
Results
After a median follow up of 37.8 months (range, 6.6 - 136.1 months), the 5-year and 10-year survival rates for the 38 patients with early and locally advanced squamous and cloacogenic carcinoma (squamous cell carcinoma and cloacogenic carcinoma) were 74.8% and 66.5%, respectively. The 5-year survival and disease-free survival rates (DFS) of the 31 patients who received chemoradiation therapy (CRT) were 83.6% and 74.3%, respectively. The overall and DFS could not be determined for the adenocarcinoma group due to the small number of cases (n = 8). Univariate analysis showed that tumor size (p = 0.04) and inguinal node status (p = 0.04) significantly influenced patient survival in patients with squamous cell and cloacogenic carcinomas. Furthermore, univariate analysis also showed that, inguinal node status influenced patient survival in the adenocarcinoma group. Multivariate analysis showed that inguinal node metastasis is a single independent prognostic variable for survival (p = 0.04) in patients with squamous cell and cloacogenic carcinomas.
Conclusion
Combined CRT has been adopted as standard treatment with outcomes that are comparable to those reported in randomized clinical trials. Due to the rarity and complexity of anal canal carcinoma, interdepartmental cooperation is required for disease treatment. Thus, proper treatment of patients should incorporate a team-approach and should be available to as many patients as possible.
doi:10.3349/ymj.2007.48.5.827
PMCID: PMC2628150  PMID: 17963341
Anal canal cancer; neoplasm; chemotherapy; radiotherapy
24.  Therapeutic Effect of 0.03% Tacrolimus Ointment for Ocular Graft versus Host Disease and Vernal Keratoconjunctivitis 
Purpose
To determine whether topical tacrolimus might prove effective in the treatment of refractory anterior segment inflammatory diseases, and to evaluate its efficacy in eyes with ocular graft versus host disease (GVHD), and vernal keratoconjunctivitis (VKC).
Methods
Twenty-eight eyes of 14 patients with anterior segment inflammation refractory to steroid treatment were treated with 0.03% tacrolimus ointment at the Samsung Medical Center, Seoul, Korea from March 2008 through August 2009. Seven patients had ocular GVHD and seven had VKC. We evaluated the conjunctival and corneal inflammatory change at one, two, four, and eight weeks after treatment with a scoring system. Time to initial response of treatment and therapeutic effect between GVHD and VKC was also analyzed. After the eight-week treatment period, patients were divided into two groups (maintenance group and discontinuance group). Eight patients maintained the treatment for an additional four months, and six patients discontinued the treatments. Therapeutic effect was also compared between the groups at eight weeks and six months after treatment.
Results
The mean conjunctival and corneal inflammation score was reduced significantly at eight weeks after treatment (p < 0.0001). The therapeutic effect in conjunctival inflammation was first noted at week two after the initial treatment (p = 0.002); reduction in corneal inflammation was first noted at one week (p = 0.0009). When compared according to diagnosis, no therapeutic difference was detected between the groups (p > 0.05). Six months after treatment, we noted no therapeutic differences between the maintenance group and discontinuance group (p > 0.05).
Conclusions
0.03% tacrolimus ointment was safe and effective for use in anterior segment inflammatory disease refractory to steroid.
doi:10.3341/kjo.2012.26.4.241
PMCID: PMC3408527  PMID: 22870021
Allergic conjunctivitis; Graft vs host disease; Tacrolimus
25.  Brain abscess in Korean children: A 15-year single center study 
Korean Journal of Pediatrics  2010;53(5):648-652.
Purpose
A brain abscess is a serious disease of the central nerve system. We conducted this study to summarize the clinical manifestations and outcomes of brain abscesses.
Methods
A retrospective chart review of pediatric patients diagnosed with brain abscesses from November 1994 to June 2009 was performed at Samsung Medical Center, Seoul, Korea.
Results
Twenty-five patients were included in this study. On average, 1.67 cases per year were identified and the median age was 4.3 years. The common presenting clinical manifestations were fever (18/25, 72%), seizure (12/25, 48%), altered mental status (11/25, 44%), and signs of increased intracranial pressure (9/25, 36%). A total of 14 (56%) patients had underlying illnesses, with congenital heart disease (8/25, 32%) as the most common cause. Predisposing factors were identified in 15 patients (60%). The common predisposing factors were otogenic infection (3/25, 12%) and penetrating head trauma (3/25, 12%). Causative organisms were identified in 64% of patients (16/25). The causative agents were S. intermedius (n=3), S. aureus (n=3), S. pneumoniae (n=1), Group B streptococcus (n=2), E. coli (n=1), P. aeruginosa (n=1), and suspected fungal infection (n=5). Seven patients received medical treatment only while the other 18 patients also required surgical intervention. The overall fatality rate was 16% and 20% of patients had neurologic sequelae. There was no statistical association between outcomes and the factors studied.
Conclusion
Although uncommon, a brain abscess is a serious disease. A high level of suspicion is very important for early diagnosis and to prevent serious consequences.
doi:10.3345/kjp.2010.53.5.648
PMCID: PMC2994128  PMID: 21189932
Brain; Abscess; Child; Korea

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