Increased Risk of Osteoporotic Fracture in Postgastrectomy Gastric Cancer Survivors Compared With Matched Controls: A Nationwide Cohort Study in Korea.

OBJECTIVES: Gastrectomy can lead to bone loss. Previous studies have suggested that there is an increased risk of fracture in gastric cancer survivors. However, these studies were performed without proper control groups. Therefore, we used Korean national health insurance data to compare the fracture risk in gastric cancer survivors who received gastrectomy to that of the general population. METHODS: A total of 133,179 gastric cancer survivors were included and matched to noncancer controls using 1:1 propensity score matching. Cox proportional hazards regression analysis was used to determine the relative risk of fracture between the gastric cancer survivors and matched controls. We also examined the factors associated with fracture in gastric cancer survivors. RESULTS: Compared with the matched controls, gastric cancer survivors had an elevated risk of osteoporotic fracture (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.53-1.70), which was most prominent in patients who underwent total gastrectomy (HR 2.18, 95% CI 1.96-2.44) and adjuvant chemotherapy (HR 2.01, 95% CI 1.81-2.23). In multivariate analysis, anemia was significantly associated with increased fracture risk (aHR 1.34, 95% CI 1.13-1.59), while decrease in weight >5% was not (aHR 1.06, 95% CI 0.89-1.25). DISCUSSION: Gastric cancer survivors who underwent gastrectomy had an increased osteoporotic fracture risk than did matched controls. Total gastrectomy, adjuvant chemotherapy, and anemia were associated with an even higher risk in these patients. Additional studies are needed to establish optimal strategies, such as screening for osteoporosis and preventive interventions, that will reduce fracture risk in this population.

Risk of Coronary Heart Disease and Ischemic Stroke Incidence in Gastric Cancer Survivors: A Nationwide Study in Korea.

BACKGROUND: Small studies suggest improvement of cardiovascular risk profiles and reduced cardiovascular mortality after gastrectomy for gastric cancer. In our study using national health insurance data, we investigated coronary heart disease (CHD) and ischemic stroke incidence among gastric cancer patients who received gastrectomy compared with general population controls. METHODS: A total of 98,936 gastric cancer patients were included in the study and matched to non-cancer controls via 1:1 propensity score matching. Competing risk regression analysis was used to determine the relative risk of CHD and ischemic stroke, with cancer mortality as the competing risk. Changes in cardiovascular risk profile before and after gastrectomy were tested, and factors associated with CHD or ischemic stroke incidence among gastric cancer patients were analyzed. RESULTS: Compared with the matched controls, gastric cancer patients who received gastrectomy were shown to have a decreased risk for both CHD (subdistribution hazard ratio [SHR] 0.60, 95% confidence interval [CI] 0.57-0.63) and ischemic stroke (SHR 0.72, 95% CI 0.69-0.75). Decreases in body mass index (BMI), blood pressure, blood sugar, and lipid and hemoglobin levels were marked after gastrectomy. Among gastric cancer patients, those who lost > 5% of their body weight were at lower risk of developing CHD (SHR 0.82, 95% CI 0.71-0.96) and ischemic stroke (SHR 0.85, 95% CI 0.75-0.98). CONCLUSIONS: CHD and ischemic stroke risk decreased after gastrectomy. The amount of weight loss and accompanying metabolic changes seemed to mediate the reduction of such risk. Reassessment of cardiovascular risk factors after gastrectomy and consideration of cardiovascular risk in the selection of treatment modality are suggested.

High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers.

UNLABELLED: Screening for hepatocellular carcinoma (HCC) is clinically important given that its early detection has remarkable survival benefits. We investigated the possible role of FIB-4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers 40 years of age or older who visited Seoul National University Hospital for a health checkup. National medical service claims data were used to determine HCC incidence. Median follow-up time was 5.4 years (interquartile range: 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and antiviral medication for hepatitis B, compared to subjects with FIB-4 <1.25, subjects with 1.7≤ FIB-4 <2.4 showed an adjusted hazard ratio (aHR) of 4.57 (95% confidence interval [CI]: 1.50-13.92) and subjects with FIB-4 ≥2.4 showed an aHR of 21.34 (95% CI: 7.73-58.92) for HCC incidence. FIB-4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C-index: 0.701 vs. 0.831; P = 0.001). FIB-4 was also better predictive of HCC incidence, compared to that of ultrasonographic liver cirrhosis (C-index: 0.775 vs. 0.701; P = 0.040). CONCLUSION: High FIB-4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB-4 is a promising, easily applicable, and cost-effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests that FIB-4 may play a valuable role in HCC screening among HBsAg carriers.

Cause of Death in Korean Men with Prostate Cancer: an Analysis of Time Trends in a Nationwide Cohort.

Despite rapid increase in incidence of prostate cancer (PC) and PC survivors, there are few studies regarding competing causes of death and time trends in Asian population. We conducted a cohort study of 2% nationwide random sample of Korean National Health Insurance employees. A total of 873 patients who had received active treatments, including surgery, radiation therapy (RT) and androgen deprivation therapy (ADT), for newly diagnosed PC between 2003 and 2010 were included. The cause of death was categorized as PC, other cancers, cardiovascular disease, and other causes. During a median follow-up of 4.75 years, 29.4% (257/873) of the study population died. PC, other cancers, cardiovascular disease, and other causes were responsible for 46.3%, 35.4%, 6.6%, and 11.7%, respectively, of the decedents. Significant differences existed in the cause of death among treatment groups (P < 0.001). Only 20% and 9.5% of surgery and RT group died of PC, whereas 63.9% of ADT group died of PC. Other cancers were responsible for 56%, 74.6% and 17.8% of death in the surgery, RT and ADT group, respectively, while cardiovascular disease accounted for 4%, 6.3%, and 7.1% of death in the treatment groups. Analysis of time trends showed that PC-specific death tended to decrease (from 42.9% in 2003 to 23.1% in 2010), whereas non-PC causes tended to increase over the 8 years. Our results are valuable in overviewing causes of death and time trends in Korean PC patients, and planning future health policy for PC.

National Practice Pattern and Time Trends in Treatment of Upper Urinary Tract Calculi in Korea: a Nationwide Population-Based Study.

Despite high prevalence of upper urinary tract calculi (UUTC), there are few studies regarding patterns of care in Asian populations. We investigated treatment patterns and time trends in patients with newly diagnosed UUTC in Korea using the National Health Insurance database that includes de-identified claims from a random 2% sample of the entire population (> 1 million people). A total of 14,282 patients who received active treatments, including shock wave lithotripsy (SWL), ureteroscopic surgery (URS), percutaneous nephrolithotomy (PNL), and uretero/pyelolithotomy (UPL), for newly diagnosed UUTC between 2003 and 2013 were included. The number of primary and all treated cases of UUTC significantly (43% and 103.3%, respectively) increased over the 10-year period. While patients undergoing SWL, URS, PNL, and UPL as primary treatment increased by 43.7%, 31.9%, 87.5%, and 0%, respectively, the relative proportion undergoing each treatment remained constant over the 10 years (SWL > 90%, URS 4.5% to 7.8%, PNL 0.4% to 1.0%, and UPL < 0.4%, respectively). Multinomial logistic regression analysis showed that age > 40 years (compared to age < 30 years) was significantly associated with URS, PNL, and UPL, rather than SWL, while patients living in urban or suburban/rural areas (compared to metropolitan) were significantly less likely to undergo URS and PNL. In summary, the majority of Korean patients underwent SWL as primary treatment for UUTC, and the predominant use of SWL remained steady over a 10-year period in Korea. Our results will be valuable in examining treatment patterns and time trends in Korean UUTC patients.

Prediction of future hepatocellular carcinoma incidence in moderate to heavy alcohol drinkers with the FIB-4 liver fibrosis index.

BACKGROUND: Although heavy alcoholics are at heightened risk for hepatocellular carcinoma (HCC), there are no guidelines that recommend HCC screening for heavy alcoholics. This study investigated FIB-4, a noninvasive and easily applicable liver fibrosis index, as a risk factor for HCC incidence among alcohol drinkers without viral hepatitis. METHODS: This retrospective cohort study included 6661 generally healthy adults who were 30 years old or older, did not have chronic viral hepatitis, and visited Seoul National University Hospital for a general, routine health evaluation. The future HCC incidence was determined from National Health Insurance medical service claims data (median follow-up, 6.2 years). RESULTS: With adjustments for age, sex, body mass index, smoking, and alcohol, compared with subjects with FIB-4 values less 1.00, subjects with FIB-4 values greater than or equal to 1.75 and less than 2.10 and subjects with FIB-4 values greater than or equal to 2.10 had adjusted hazard ratios (aHRs) of 5.18 (95% confidence interval [CI], 1.12-24.00) and 13.63 (95% CI, 3.77-49.33), respectively, for HCC incidence. This was heightened in subjects who drank more 30 g of alcohol per day: the aHRs were 8.39 (95% CI, 1.28-54.87) and 16.58 (95% CI, 3.87-71.04), respectively. FIB-4 was shown to have a higher predictive value for HCC incidence than ultrasonographically detected liver cirrhosis (C-index, 0.665 vs 0.527; P = .044). CONCLUSIONS: High FIB-4 is a risk factor with a high predictive value for HCC incidence, especially among moderate to heavy alcoholics (>30 g/d). FIB-4 is a readily available and probably cost-effective clinical tool with potential value for identifying subpopulations of alcoholics at particularly high risk who would benefit from regular HCC screening. Further investigations are warranted to validate our results; nonetheless, our study suggests that FIB-4 may be useful in HCC screening among alcoholics.

Attitudes toward disclosure of medication side effects: a nationwide survey of Korean patients, caregivers, and oncologists.

BACKGROUND: We aimed to compare the views of cancer patients, family caregivers, and oncologists about the disclosure of side effects in respect to their probability of occurrence, severity, and treatment purpose. We also compared attitudes toward potential harm of side effect disclosure, patients' perceived ability to understand the risk of the side effects, and informed decision-making regarding side effects. METHODS: A national survey was performed with 750 patient-caregiver dyads (75.5% participation rate) recruited by 134 oncologists in 13 cancer centers (93% participation rate). Attitudes toward communication of side effects were assessed in terms of drug purpose, severity of potential complications, and probability of harm. RESULTS: Most patients (82.1-87.0%) and caregivers (75.9-81.5%) thought they should be informed of all possible drug side effects regardless of risk, severity, or drug purpose and wanted these risks to be communicated explicitly. Patients and their caregivers believed that detailed explanations of side effects did not harm patients, and further, they believed that patients could understand risks and make treatment decision based on that information. In contrast, oncologists held less positive attitudes toward providing detailed information about drug side effects, especially if they were not severe and if the drugs were designed for supportive care. CONCLUSION: Cancer patients and family members had different perspectives and preferences regarding communication of drug side effects from their oncologists. The data from our study can serve as a guide for oncologists in presenting side effects information to their patients, as well as a basis for physician training.

Depression and Its Severity Are Strongly Associated with Both Storage and Voiding Lower Urinary Tract Symptoms Independently of Prostate Volume.

Depression is related to various functional medical conditions. Its association with lower urinary tract symptoms (LUTS) is also expected. We evaluated whether depression and its severity are associated with LUTS when LUTS risk factors including prostate volume (PV) are taken into account in a large population of Korean men. Study subjects included 10,275 men who underwent routine health check-ups at the Healthcare System Gangnam Center of Seoul National University Hospital. Depression was assessed using Beck Depression Inventory-II and LUTS using international prostate symptom score. PV was measured using transrectal ultrasonography by a radiologist. Effect sizes of depression severity on total, storage, and voiding symptoms were assessed. In multivariate logistic regression analysis, mild, moderate and severe depression were associated with total (adjusted odds ratio: aOR = 2.99, 3.86 and 8.99; all P < 0.001), voiding (aOR = 3.04, 3.28 and 5.58; all P < 0.001) and storage symptoms (aOR = 2.43, 3.43 and 2.89; all P < 0.05) showing dose response relationships (all P trend < 0.001). In a subgroup analysis for participants with PV data (n = 1,925), mild and moderate-severe depression were also associated with LUTS (aOR = 3.29, 2.84; P < 0.001 and 0.018, respectively). In conclusion, depression and its severity are strongly associated with total, voiding, and storage symptoms independently of PV state.

Treatment Gap in the National Health-screening Program in Korea: Claim-based Follow-up of Statin Use for Sustained Hypercholesterolemia.

Participation in a screening program by itself may not improve clinical outcomes. Treatment gaps in the program may limit its full benefit. We evaluated statin prescription rates for subjects with sustained hypercholesterolemia to assess the treatment gaps in the National Health Screening Program (NHSP) in Korea. A retrospective, random cohort was established among National Health Insurance Corporation (NHIC) members. Finally, we examined 465,499 individuals who attended the NHSP from 2003 to 2010 without any history of dyslipidemia, statin prescription, or hospitalization for cardiovascular events until the end of 2002. The subsequent statin prescription rates were identified from the NHIC medical service claim database from 2003 to 2011. Descriptive data and odds ratio from multivariate logistic analyses on statin prescription rates and the corresponding correlations were evaluated. The NHSP detected 114,085 (24.5%) cases of newly diagnosed hypercholesterolemia. However, only 8.6% of these received statin prescription within 6 months of diagnosis. For cases of sustained hypercholesterolemia determined in the next screening visit by the NHSP, the statin prescription rate increased, but only to 12.2%. Statin prescriptions were more common among females, older individuals, and hypertension or diabetes patients. Furthermore, the statin prescription rates had increased over the study period. The NHSP exhibited low statin prescription rate which has been improving. For the NHSP to be effective, it would be worthwhile to decrease the gap between the diagnosis of hypercholesterolemia and the following treatment.

Establishment of Reference Ranges for Prostate Volume and Annual Prostate Volume Change Rate in Korean Adult Men: Analyses of a Nationwide Screening Population.

We aimed to determine normal reference ranges for prostate volume (PV) and annual PV change rate in a Korean nationwide screening population. Data from men who underwent a routine health check-up were collected from 13 university hospitals. The cohort comprised men aged ≥40 yr who had undergone 2 or more serial transrectal ultrasonographies. Men with initial PV>100 mL; serum PSA level>10 ng/mL; PV reduction>20% compared with initial PV, or who had history of prostate cancer or prostate surgery, were excluded. Linear regression and mixed effects regression analyses were used to predict mean PV and longitudinal change in PV over time. A total of 2,967 men formed the study cohort. Age, body mass index (BMI), and serum prostate-specific antigen (PSA) level were found to be significant predictors of PV. A predicted PV table, with a 95% confidence interval (CIs), was developed after adjusting for these 3 variables. Annual PV change rate was 0.51 mL/year (95% CI, 0.47-0.55). Annual PV change rate according to age was 0.68 mL/year, 0.84 mL/year, 1.09 mL/year, and 0.50 mL/year for subjects in their 40s, 50s, 60s, and ≥70 yr, respectively. Predicted annual PV change rate differed depending on age, BMI, serum PSA level and baseline PV. From a nationwide screening database, we established age-, PSA-, and BMI-specific reference ranges for PV and annual PV change rate in Korean men. Our newly established reference ranges for PV and annual PV change rate will be valuable in interpreting PV data in Korean men.

Alcohol is longitudinally associated with lower urinary tract symptoms partially via high-density lipoprotein.

BACKGROUND: Previous studies on the association of alcohol consumption with lower urinary tract symptoms (LUTS) have been inconsistent, and none took into account the dynamic nature of LUTS, fluctuating over time. The purpose of the study was to determine the longitudinal association of alcohol consumption with LUTS. METHODS: We used generalized estimating equations to analyze the longitudinal association of alcohol consumption with LUTS in a longitudinal study of 9,712 healthy men 30 years or older who visited our institution multiple times for routine comprehensive health evaluations, with an average follow-up period of 27.9 months. RESULTS: Light-moderate alcohol consumption (0.1 to 29 g/d) was associated with decreased likelihood of moderate-severe LUTS, whereas heavy alcohol consumption (≥30 g/d) was associated with increased likelihood of moderate-severe LUTS in a dose-dependent manner. Compared to those with 0 g/d alcohol intake, subjects who drank 0.1 to 9.9, 10 to 19.9, 20 to 29.9, 30 to 39.9, or ≥40 g/d of alcohol were in general significantly associated with moderate-severe LUTS with adjusted odds ratio (95% confidence interval) as follows respectively: 0.94 (0.87 to 1.02), 1.00 (0.91 to 1.09), 0.85 (0.77 to 0.93), 1.08 (0.98 to 1.19), and 1.31 (1.19 to 1.44). However, the protective association of light-moderate alcohol consumption with LUTS was greatly attenuated when serum high-density lipoprotein (HDL) was added to the analysis, specifically for voiding symptoms. CONCLUSIONS: We show strong evidence there is longitudinal association of alcohol consumption with LUTS. The protective effect of light-moderate alcohol consumption on LUTS is in part modulated by HDL as a confounder, similar to its effect on coronary heart disease.

CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function.

Myeloid-derived suppressor cells (MDSCs) are a subpopulation of myeloid cells with immunosuppressive function whose numbers are increased in conditions such as chronic infection, trauma, and cancer. Unlike murine MDSCs defined as CD11b(+)/Gr-1(+), there are no specific markers for human MDSCs. The goal of this study was to delineate a specific human MDSCs subpopulation in granulocytes from terminal cancer patients and investigate its clinical implications. Here, we show that the CD15(+)/CD16(low) subset was increased in terminal cancer patients compared with healthy donors (P = 0.009). Phorbol 12-myristate 13-acetate-activated granulocytes (CD16(low)/CD66b(++)/CD15(+)) that have a phenotype similar to MDSCs from cancer patients, effectively suppressed both proliferation and cytotoxicity of normal T cells. Among cancer patients, T-cell proliferation was highly suppressed by granulocytes isolated from terminal cancer patients with a high proportion of CD15(+)/CD16(low) cells. Patients with low peripheral blood levels of CD15(+)/CD16(low) cells had significantly longer survival than those with high levels (P = 0.0011). Patients with higher levels of CD15(+)/CD16(low) also tended to have poor performance status (P = 0.05). These data suggest that CD15(+)/CD16(low) granulocytes found in terminal cancer patients may play a role in the progression of cancer by inhibiting tumor immunity.

Mode of primary cancer detection as an indicator of screening practice for second primary cancer in cancer survivors: a nationwide survey in Korea.

BACKGROUND: While knowledge and risk perception have been associated with screening for second primary cancer (SPC), there are no clinically useful indicators to identify who is at risk of not being properly screened for SPC. We investigated whether the mode of primary cancer detection (i.e. screen-detected vs. non-screen-detected) is associated with subsequent completion of all appropriate SPC screening in cancer survivors. METHODS: Data were collected from cancer patients treated at the National Cancer Center and nine regional cancer centers across Korea. A total of 512 cancer survivors older than 40, time since diagnosis more than 2 years, and whose first primary cancer was not advanced or metastasized were selected. Multivariate logistic regression was used to examine factors, including mode of primary cancer detection, associated with completion of all appropriate SPC screening according to national cancer screening guidelines. RESULTS: Being screen-detected for their first primary cancer was found to be significantly associated with completion of all appropriate SPC screening (adjusted odds ratio, 2.13; 95% confidence interval, 1.36-3.33), after controlling for demographic and clinical variables. Screen-detected cancer survivors were significantly more likely to have higher household income, have other comorbidities, and be within 5 years since diagnosis. CONCLUSIONS: The mode of primary cancer detection, a readily available clinical information, can be used as an indicator for screening practice for SPC in cancer survivors. Education about the importance of SPC screening will be helpful particularly for cancer survivors whose primary cancer was not screen-detected.

A possible mechanism of impaired NK cytotoxicity in cancer patients: down-regulation of DAP10 by TGF-beta1.

AIMS AND BACKGROUND: Elevated TGF-BETA1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. However, the molecular mechanism of immunosuppression by TGF-BETA1 is not yet clarified. METHODS: IL-2-activated human NK cells were cultured with TGF-BETA1. Protein levels of NKG2D and DAP10 were examined by FACS or immunoblot analyses. Real-time RTPCR was performed to quantify the transcription levels. MAPK inhibitors were used to investigate intracellular signaling. RESULTS: TGF-BETA1 down-regulated total and surface NKG2D, which was partially dependent on transcriptional regulation. TGF-BETA1 treatment of human NK cells resulted in significant changes in both transcriptional and translational levels of DAP10. Moreover, treatment with bafilomycin A1 or folimycin restored total NKG2D levels in TGF-BETA1-treated NK cells. The impaired NKG2D down-modulation by TGF-BETA1 was not associated with activation of the MAPK signaling pathway. CONCLUSIONS: TGF-BETA1 down-modulates surface NKG2D expression by controlling the transcriptional and translational levels of DAP10.

Accuracy and efficiency of an artificial intelligence tool when counting breast mitoses.

BACKGROUND: The mitotic count in breast carcinoma is an important prognostic marker. Unfortunately substantial inter- and intra-laboratory variation exists when pathologists manually count mitotic figures. Artificial intelligence (AI) coupled with whole slide imaging offers a potential solution to this problem. The aim of this study was to accordingly critique an AI tool developed to quantify mitotic figures in whole slide images of invasive breast ductal carcinoma. METHODS: A representative H&E slide from 320 breast invasive ductal carcinoma cases was scanned at 40x magnification. Ten expert pathologists from two academic medical centers labeled mitotic figures in whole slide images to train and validate an AI algorithm to detect and count mitoses. Thereafter, 24 readers of varying expertise were asked to count mitotic figures with and without AI support in 140 high-power fields derived from a separate dataset. Their accuracy and efficiency of performing these tasks were calculated and statistical comparisons performed. RESULTS: For each experience level the accuracy, precision and sensitivity of counting mitoses by users improved with AI support. There were 21 readers (87.5%) that identified more mitoses using AI support and 13 reviewers (54.2%) that decreased the quantity of falsely flagged mitoses with AI. More time was spent on this task for most participants when not provided with AI support. AI assistance resulted in an overall time savings of 27.8%. CONCLUSIONS: This study demonstrates that pathology end-users were more accurate and efficient at quantifying mitotic figures in digital images of invasive breast carcinoma with the aid of AI. Higher inter-pathologist agreement with AI assistance suggests that such algorithms can also help standardize practice. Not surprisingly, there is much enthusiasm in pathology regarding the prospect of using AI in routine practice to perform mundane tasks such as counting mitoses.

Increased cardiovascular risk in thyroid cancer patients taking levothyroxine: a nationwide cohort study in Korea.

Objective Many thyroid cancer patients are exposed to long-term thyroid-stimulating hormone (TSH) suppression, often as lifetime treatment, and are consequently at risk for cardiovascular disease. We investigated the incidence of coronary heart disease (CHD) and ischemic stroke among thyroid cancer patients compared with matched control subjects. Design Retrospective cohort study. Methods A total of 182 419 subjects who received thyroidectomy for thyroid cancer during 2004-2012 were selected from the Korean National Health Insurance data, which cover approximately 97% of the entire Korean population. Propensity score matching was used to select non-cancer controls. Cox proportional hazards regression analysis was used to determine relative risk of coronary heart disease and ischemic stroke. Mean follow-up was 4.32 years. Results Thyroid cancer patients had elevated risk for CHD and ischemic stroke with hazard ratio (HR) of 1.15 (95% confidence interval (CI): 1.10-1.22) and 1.15 (1.09-1.22), respectively. This risk was increased in those who took a higher dosage of levothyroxine (HR: 1.47, 95% CI: 1.34-1.60 for CHD and HR: 1.56, 95% CI: 1.42-1.72 for ischemic stroke among those who took ≥170 µg/day levothyroxine). Although risk of atrial fibrillation was dose-dependently associated with levothyroxine dosage, it represents only a small proportion of ischemic stroke incidence (4.4%, 128/2914). Conclusions The risk for CHD and ischemic stroke was higher in thyroid cancer patients who received thyroidectomy, and the dosage of levothyroxine administered appears to play a major role. Greater caution is suggested for the screening and treatment of thyroid cancer and subsequent TSH suppression therapy, as well as proper management for cardiovascular disease prevention.

Trend Analysis for the Choice and Cost of Lung Cancer Treatment in South Korea, 2003-2013.

PURPOSE: Our study aimed to report the annual changes in lung cancer statistics and analyze trends in sociodemographic, medical, and financial factors from 2003 to 2013 in the national database from the Korean National Health Insurance (KNHI). MATERIALS AND METHODS: Among 7,489 patients with code C34 in KNHI database, only lung cancer patients newly diagnosed after 2003 were included in the study population, for a total of 4,582 patients. Descriptive statistics were used to characterize treatment patterns and medical costs according to sociodemographic factors. RESULTS: Approximately 70% of subjects were male, and the mean age was 67 years. Around 46% of patients were over 70 years old, and 12% were over 80 years old. The medical costs were highest for patients younger than 60 and lowest for those over 80 years old. Surgery was more common in younger patients, while "no treatment" increased greatly with age. In trend analysis, the proportions of aging (p for trend < 0.001), female (p for trend=0.003), metropolitan/urban (p for trend=0.041), and lowest or highest-income patients (p for trend=0.004) increased over time, along with the prevalence of surgery as the primary treatment (p for trend < 0.001). There was also a trend with regard to change in medical costs (p for trend < 0.001), in that those of surgery and radiotherapy increased. CONCLUSION: Surgery as a curative treatment has increased over the past decade. However, the elderly, suburban/rural residents, and low-income patients were more likely to be untreated. Therefore, active measures are required for these increasingly vulnerable groups.

J-Shaped Association Between Postoperative Levothyroxine Dosage and Fracture Risk in Thyroid Cancer Patients: A Retrospective Cohort Study.

Long-term administration of supraphysiologic dosages of levothyroxine can have detrimental effect on the bone. We aimed to investigate fracture incidence among post-thyroidectomy thyroid cancer patients compared with a matched comparison group, and explore the association between levothyroxine dosage and fracture risk. From the Korean National Health Insurance database, virtually all thyroid cancer patients who received thyroidectomy in Korea from January 1, 2004 to December 31, 2012 were included. Matched subjects were selected by 1:1 propensity score matching. Cox proportional hazards regression analysis was used to determine relative risk of osteoporotic fracture. Of 185,956 thyroid cancer patients identified, fracture events were observed in 1096 subjects (0.56%) over a mean 4.35 years of follow-up. Compared to the matched comparison group, thyroid cancer patients had no elevated risk of osteoporotic fracture (hazard ratio [HR] 1.03; 95% confidence interval [CI], 0.94 to 1.12); however, the highest dosage group (≥170 µg/day) showed significantly higher risk (HR 1.25; 95% CI, 1.07 to 1.45), while the second quartile dosage group (115-144 µg/day) showed lower risk (HR 0.71; 95% CI, 0.59 to 0.84) compared to a matched comparison group. When the second quartile dosage group was considered as reference, increased fracture risk was observed in those who took either lower (first quartile: adjusted HR 1.31; 95% CI, 1.08 to 1.59) or higher dosage of levothyroxine (third quartile: adjusted HR 1.50; 95% CI, 1.26 to 1.79; fourth quartile: adjusted HR 1.79; 95% CI, 1.51 to 2.13). Thyroid cancer patients were more likely to be treated with osteoporosis medication (HR 1.22; 95% CI, 1.18 to 1.26) than the matched comparison group. Both high and low dosage of levothyroxine treatment was associated with a higher risk for fractures in a J-shaped dose-dependent manner in post-thyroidectomy patients. Future studies are needed to determine how to optimize thyroid-stimulating hormone (TSH) suppression and how to screen and manage fracture risk. © 2018 American Society for Bone and Mineral Research.

Incidentally detected atherosclerosis in the abdominal aorta or its major branches on computed tomography is highly associated with coronary heart disease in asymptomatic adults.

BACKGROUND: Atherosclerotic lesions in the abdominal aorta or its major branches are often incidentally detected on abdominal CT. However, clinical implications and optimal subsequent management are mostly left undetermined. METHODS: Consecutive, asymptomatic adults (age≥30) who underwent both abdominal CT and coronary computed tomography angiography as part of a self-referred health check-up were investigated (n = 1494). RESULTS: Adjusted for cardiovascular risk factors, abdominal atherosclerotic lesions with stenosis<25% were associated with significant coronary stenosis, especially in the abdominal aorta (adjusted odds ratio [aOR] 3.37, 95% confidence interval [CI] 0.99-11.45) and any common iliac artery (aOR 2.99, 95% CI 1.43-6.26). The association was higher in atherosclerotic lesions with stenosis≥25%, respectively (aOR 16.39, 95% CI 4.00-67.11; aOR 7.32, 95% CI 2.84-18.86). Furthermore, any major abdominal artery stenosis added predictive value to significant coronary stenosis (area under the receiver operating curve: 0.7598 vs. 0.8019, P < 0.001). The extent of arterial territory involvement was associated with the presence of significant coronary stenoses (P for trend <0.001). CONCLUSION: Stenotic atherosclerotic lesions in the abdominal aorta or its major branches incidentally detected on abdominal CT are relatively prevalent and carry high risk for asymptomatic coronary arterial disease.