Shock index and shock index, pediatric age-adjusted as predictors of mortality in pediatric patients with trauma: A systematic review and meta-analysis.

This study aimed to assess the predictive ability of the shock index (SI) and the shock index, pediatric age-adjusted (SIPA) for mortality among pediatric patients with trauma (aged ≤ 18 years). A systematic search used PubMed, Embase, and Cochrane Library databases to identify pertinent articles published from their inception to 13 February 2023. For each SI and SIPA, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals were calculated. We planned a priori meta-regression analyses to explore heterogeneity using the following covariates: country, clinical setting, type of center, data source, and cutoff value. Twelve studies were included based on the inclusion criteria. Among them, nine studies with 195,469 patients were included for the SIPA at the hospital, four studies with 4,970 patients were included for the pre-hospital SIPA, and seven studies with 606,445 patients were included to assess the ability of the SI in predicting mortality. The pooled sensitivity and specificity with 95% confidence interval for predicting mortality were as follows: 0.58 (0.44-0.70) and 0.72 (0.60-0.82), respectively, for the SIPA at the hospital; 0.61 (0.47-0.74) and 0.67 (0.61-0.73), respectively, for the pre-hospital SIPA; and 0.71 (0.59-0.81) and 0.45 (0.31-0.59), respectively for the SI. The DOR were 3.80, 3.28, and 2.06 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The AUC were 0.693, 0.689, and 0.618 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The SI and SIPA are simple predictive tools with sufficient accuracy that can be readily applied to pediatric patients with trauma, but SIPA and SI should be utilized cautiously due to their limited sensitivity and specificity, respectively.

Resting-state prefrontal EEG biomarker in correlation with postoperative delirium in elderly patients.

Postoperative delirium (POD) is associated with adverse outcomes in elderly patients after surgery. Electroencephalography (EEG) can be used to develop a potential biomarker for degenerative cerebral dysfunctions, including mild cognitive impairment and dementia. This study aimed to explore the relationship between preoperative EEG and POD. We included 257 patients aged >70 years who underwent spinal surgery. We measured the median dominant frequency (MDF), which is a resting-state EEG biomarker involving intrinsic alpha oscillations that reflect an idle cortical state, from the prefrontal regions. Additionally, the mini-mental state examination and Montreal cognitive assessment (MoCA) were performed before surgery as well as 5 days after surgery. For long-term cognitive function follow up, the telephone interview for cognitive status™ (TICS) was performed 1 month and 1 year after surgery. Fifty-two (20.2%) patients were diagnosed with POD. A multivariable logistic regression analysis that included age, MoCA score, Charlson comorbidity index score, Mini Nutritional Assessment, and the MDF as variables revealed that the MDF had a significant odds ratio of 0.48 (95% confidence interval 0.27-0.85). Among the patients with POD, the postoperative neurocognitive disorders could last up to 1 year. Low MDF on preoperative EEG was associated with POD in elderly patients undergoing surgery. EEG could be a novel potential tool for identifying patients at a high risk of POD.

Association Between Migraine and Ischemic Cardio-Cerebrovascular Disease (CCVD) and Effects of Triptans and Ergotamine on the Risk of Ischemic CCVD in Patients with Migraine in the Korean NHIS-HEALS Cohort.

BACKGROUND AND OBJECTIVES: Triptans and ergotamine are commonly used to treat migraine, a risk factor for ischemic stroke. This study aimed to investigate the association between migraine and ischemic cardio-cerebrovascular disease (CCVD). Further analyses were performed to examine whether symptom-relieving treatment of migraine with triptans and ergotamine reduces ischemic CCVD in migraineurs. METHODS: Participants from the Korean NHIS-HEALS cohort database were divided into patients reporting headache without migraine (HA), migraineurs who received at least one prescription for triptans or ergotamine (TE), and migraineurs who were prescribed neither triptans nor ergotamine (NTNE). Ischemic CCVDs comprised ischemic cerebrovascular diseases and cardiovascular diseases. Using cox proportional hazards regression models, primary and secondary analysis for risk of ischemic CCVDs was compared. RESULTS: Among 62,272 patients diagnosed with migraine or HA, men with migraine or HA numbered 14,747 and 8935, respectively, while the numbers of women were 27,836 and 10,754, respectively. The median follow-up was 6.65 years. The overall incidence rate of CCVDs was 4728/38,590 (12.25%) in females and 3158/23,682 (13.33%) in males. Compared with the HA group, the hazard ratios (HRs) (95% CIs) of the TE and NTNE groups for ischemic CCVDs were 1.18 (1.01-1.39) and 1.39 (1.28-1.50), respectively, in males, and 1.22 (1.09-1.37) and 1.53 (1.42-1.65), respectively, in females, after full adjustment for confounding variables. Compared with the NTNE group, the HRs (95% CIs) of the TE group for ischemic CCVDs were 0.86 (0.73-0.999) in males and 0.80 (0.72-0.88) in females. CONCLUSIONS: Migraine increased the risk of ischemic CCVDs in both sexes, and migraineurs treated with triptans and ergotamine were at lower risk of ischemic CCVDs than migraineurs who did not take those medications, especially in women.

Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort.

BACKGROUND: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor. RESEARCH DESIGN AND METHODS: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models. RESULTS: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20). CONCLUSIONS: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.

Effect of metabolic health and obesity on all-cause death and CVD incidence in Korean adults: a retrospective cohort study.

This study aimed to investigate the risk of all-cause mortality and incidence of CVD according to metabolic health and body mass index (BMI) in Korean adults. This study was retrospectively designed using the National Health Insurance Service-National Health Screening Cohort data. Participants were divided into six groups according to two category of metabolic syndrome and three categories of BMI. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite outcome (all-cause mortality and incidence of CVDs) were estimated using multivariable Cox proportional hazards regression models. 151,706 participants aged ≥ 40 years were enrolled; median follow-up period was 9.7 years in the study. Compared to metabolically healthy normal weight, the fully adjusted HRs (95% CIs) of metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese for composite outcome were 1.07 (1.03-1.12), 1.12 (1.07-1.17), 1.33 (1.25-1.41), 1.28 (1.22-1.34), and 1.31 (1.26-1.37), respectively, in men, and 1.10 (1.05-1.16), 1.22 (1.16-1.29), 1.34 (1.26-1.43), 1.27 (1.19-1.34), and, 1.40 (1.34-1.47), respectively, in women. High BMI and metabolic unhealthiness were associated with an increased risk on the composite of all-cause mortality and incidence of CVD in both sexes.

Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality.

OBJECTIVE: The prevalence of diabetes mellitus (DM), cardio-cerebrovascular diseases (CCVDs) has increased during recent decades. We aimed to investigate the relationship between body mass index (BMI) and each of several outcomes (DM, CCVDs, or mortality) based on the Korean National Health Insurance Service-Health Screening cohort. METHODS: BMI was categorized as appropriate for Asian populations, into underweight (< 18.5 kg/m2), normal (18.5-< 23 kg/m2), overweight (23-< 25 kg/m2), grade 1 obesity (25-< 30 kg/m2), grade 2 obesity (30-< 35 kg/m2), and grade 3 obesity (≥35 kg/m2). In addition, BMI was further stratified into one unit. Multivariate Cox proportional hazards regression analyses were conducted to examine the association between BMI category and the primary outcomes (DM, CCVDs, or mortality). RESULTS: A total of 311,416 individuals were included. The median follow-up was 12.5 years. Compared to normal BMI, underweight, overweight, and grade 1-3 obese individuals had a higher risk of the primary outcomes (hazard ratio [95% confidence intervals] 1.293 [1.224-1.365], 1.101 [1.073-1.129], 1.320 [1.288-1.353], 1.789 [1.689-1.897], and 2.376 [2.019-2.857], respectively, in men and 1.084 [1.010-1.163], 1.150 [1.116-1.185], 1.385 [1.346-1.425], 1.865 [1.725-2.019], and 2.472 [2.025-3.028], respectively, in women). Setting the reference BMI to 20-< 21 kg/m2 and categorizing into one unit increment, BMI was associated with the primary outcomes in a J-shaped manner in both sexes. The risk of DM increased with higher BMI in both sexes, while all-cause mortality decreased in men with a BMI 21-< 31 kg/m2 and women with BMI 22-< 30 kg/m2. CONCLUSIONS: BMI was associated with all-cause mortality in a J-shaped manner in both sexes, while it was associated with risk of DM in a dose-response relationship. The relationship between BMI and the primary outcomes was J-shaped.

Higher Pulse Pressure Is Associated With Increased Risk of Cardio-cerebrovascular Disease and All-Cause Mortality: A Korean National Cohort Study.

BACKGROUND: This study aimed to investigate the association of pulse pressure (PP) with the cardio-cerebrovascular disease (CCVD) risk and all-cause mortality according to blood pressure level using Korean national cohort data. METHODS: This study was retrospectively designed and based on the Korean National Health Insurance Service-National Health Screening Cohort. Participants aged 40-69 years at baseline were categorized into normal, elevated, stage 1, and stage 2 groups according to blood pressure. Each group was further classified into 5 groups separated by 10-mm Hg increments in PP. The primary composite outcome was defined as CCVDs and all-cause mortality. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate the composite outcome. RESULTS: During the follow-up period (median follow-up period, 12.0 years), the primary composite outcome occurred in 18,444 (15.0%) of 122,783 men and 10,096 (11.4%) of 88,550 women. After complete adjustment for confounders, in the stage 1 hypertensive men, the hazard ratio (95% confidence intervals [CIs]) of the 31-40, 41-50, 51-60, and >60 mm Hg PP groups was 1.112 (1.013-1.221), 1.035 (0.942-1.137), 1.009 (0.907-1.123), and 1.324 (1.130-1.551) in comparison with the ≤30 mm Hg PP group. In the stage 2 hypertensive men, the HRs (95% CIs) were 1.069 (0.949-1.204), 1.059 (0.940-1.192), 1.123 (0.999-1.263), and 1.202 (1.061-1.358) compared to the ≤30 mm Hg PP group. However, these associations were not significant in women. CONCLUSIONS: Hypertensive men with an increased PP have an increased risk of CCVDs and all-cause mortality.

Recent trends in opioid prescriptions in Korea from 2002 to 2015 based on the Korean NHIS-NSC cohort.

OBJECTIVES: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. METHODS: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). RESULTS: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. CONCLUSIONS: Consumption of opioids greatly increased in Korea over the 14-year study period.

Statin Use and Incidence of Chronic Kidney Disease in Hypercholesterolemia Patients with Normal Renal Function.

INTRODUCTION: Dyslipidemia is a known risk factor for chronic kidney disease (CKD). The effects of statins on CKD have already been studied in patients with CKD; however, data on the general population are limited. This study aimed to determine the relationship between statin use and the incidence of CKD in patients with hypercholesterolemia having normal renal function. METHODS: A total of 7,856 participants aged 40-79 years at baseline (2009-2010) were included in the final analyses. The participants were divided into statin users (n = 4,168) and statin nonusers (n = 3,668), according to the statin usage. The Cox proportional hazard regression model was used to evaluate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CKD. RESULTS: The median follow-up duration was 5.8 years. A total of 543 cases of CKD (285 cases in males and 258 cases in females) occurred during the study period. The estimated cumulative incidence of CKD was significantly different between male statin nonusers and users (p < 0.001), while it was not statistically significant between female statin nonusers and users (p = 0.126). Compared with statin nonusers, the fully adjusted HRs (95% CIs) for CKD in statin users were 1.014 (0.773-1.330) in males and 1.117 (0.843-1.481) in females. CONCLUSION: Dyslipidemia is an obvious risk factor for CKD; however, statin use in patients with hypercholesterolemia having normal renal function does not demonstrate a clear relationship with the incidence of CKD.

The association between triglyceride-glucose index, cardio-cerebrovascular diseases, and death in Korean adults: A retrospective study based on the NHIS-HEALS cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs and mortality. METHODS: This retrospective study included 114,603 subjects. The TyG index was categorized into four quartiles by sex: Q1, <8.249 and <8.063; Q2, 8.249‒<8.614 and 8.063‒<8.403; Q3, 8.614‒< 8.998 and 8.403‒<8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality) and secondary outcomes (cardiovascular diseases [CVDs], cerebrovascular diseases [CbVDs], CCVD-related deaths, or all-cause deaths), Cox proportional hazards regression models were adopted. RESULTS: Compared to Q1, the HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.062 (0.981‒1.150), 1.110 (1.024-1.204), and 1.151 (1.058-1.252) in men and 1.099 (0.986-1.226), 1.046 (0.938-1.166), and 1.063 (0.954-1.184) in women, respectively, after adjusted for age, smoking status, drinking status, physical activity, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, economic status, and anti-hypertensive medications. Fully adjusted HRs (95% CIs) for CVDs of Q2, Q3, and Q4 were 1.114 (0.969-1.282), 1.185 (1.031-1.363), and 1.232 (1.068-1.422) in men and 1.238 (1.017-1.508), 1.183 (0.971-1.440), and 1.238 (1.018-1.505) in women, respectively. The adjusted HRs (95% CIs) for ischemic CbVDs of Q2, Q3, and Q4 were 1.005 (0.850-1.187), 1.225 (1.041-1.441), and 1.232 (1.039-1.460) in men and 1.040 (0.821-1.316), 1.226 (0.981-1.532), and 1.312 (1.054-1.634) in women, respectively, while the TyG index was negatively associated with hemorrhagic CbVDs in women but not in men. The TyG index was not significantly associated with CCVD-related death or all-cause death in either sex. CONCLUSIONS: Elevated TyG index was positively associated with the primary outcomes (CCVDs and all-cause mortality) in men and predicted higher risk of CVDs and ischemic CbVDs in both sexes.

Positive association between the ratio of triglycerides to high-density lipoprotein cholesterol and diabetes incidence in Korean adults.

BACKGROUND: Insulin resistance is associated with the incidence of diabetes and cardiovascular diseases such as myocardial infarction. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is positively correlated with insulin resistance. This study aimed to investigate the relationship between the TG/HDL-C ratio and the incidence of diabetes in Korean adults. METHODS: This retrospective study used data from the National Health Insurance Service-National Health Screening Cohort. The TG/HDL-C ratio was divided into three tertiles, the T1, T2, and T3 groups, based on sex. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes using multivariate Cox proportional hazards regression analyses. RESULTS: A total of 80,693 subjects aged between 40 and 79 years were enrolled. The median follow-up period was 5.9 years. The estimated cumulative incidence of diabetes in the T1, T2, and T3 groups was 5.94%, 8.23%, and 13.50%, respectively, in men and 4.12%, 4.72%, and 6.85%, respectively, in women. Compared to T1, the fully adjusted HRs (95% CIs) of the T2 and T3 groups for new-onset diabetes were 1.17 (1.06-1.30) and 1.47 (1.34-1.62), respectively, in men and 1.20 (1.02-1.42) and 1.52 (1.30-1.78), respectively, in women. CONCLUSIONS: Increased TG/HDL-C ratio was significantly associated with a higher risk of new-onset diabetes in both sexes.

The ratio of triglycerides to high-density lipoprotein cholesterol is associated with the risk of chronic kidney disease in Korean men.

Dyslipidemia is nephrotoxic and can result in the development of chronic kidney disease (CKD). The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is well-correlated with insulin resistance and cardiovascular events. The aim of this study is to examine the association between the TG/HDL-C ratio and CKD in Korean adults. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening cohort. Seventy three thousand and fifty-two participants aged between 40 and 79 years old at baseline (2009-2010) were included in the final analyses. The study population was classified into three tertile groups (T1 , T2 , and T3 ) according to the TG/HDL-C ratio by sex. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were calculated using Cox proportional hazard regression models. The median follow-up duration was 5.9 years. Higher tertile groups of the TG/HDL-C ratio had lower estimated glomerular filtration rates in both sexes. The cumulative incidence of CKD of T1 , T2 , and T3 was 11.89%, 12.90%, and 12.91%, respectively, in men and 10.17%, 10.61%, and 14.87%, respectively, in women (all p values < 0.001). Compared with T1 of the TG/HDL-C ratio, the HRs (95% CIs) of T2 and T3 for CKD were 1.212 (1.118-1.315) and 1.183 (1.087-1.287), respectively, in men and 0.895 (0.806-0.994) and 1.038 (0.937-1.150), respectively, in women after being fully adjusted. Higher TG/HDL-C ratios were positively associated with CKD development in men, while middle levels of TG/HDL ratios reduced the CKD incidence in women.

Role of Preoperative Chemoradiotherapy in Clinical Stage II/III Rectal Cancer Patients Undergoing Total Mesorectal Excision: A Retrospective Propensity Score Analysis.

BACKGROUND: Although the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement. METHODS: Stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. RESULTS: A total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46-87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p<0.001). CONCLUSION: Using MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.

Better outcome of XELOX chemotherapy in patients with advanced intestinal-type adenocarcinoma of the ampulla of Vater.

Adenocarcinoma arising from the ampulla of Vater is a rare disease and has limited data regarding outcome of chemotherapy. The ampulla of Vater is a heterogeneous junctional structure located at the union of the common bile duct, the pancreatic duct, and the small intestine. Thus, ampullary adenocarcinoma is classified as either intestinal type or pancreatobiliary type. We investigated the efficacy of the XELOX (capecitabine plus oxaliplatin) chemotherapy in patients with recurrent or metastatic ampullary adenocarcinoma, and analyzed the histopathologic features and outcomes. From November 2009 to December 2011, 21 patients were treated with XELOX regimen. XELOX was administered in outpatient clinic every 3 weeks according to the following protocol: oral administration of capecitabine 750 mg/m² twice a day on days 1-14 and intravenous injection of oxaliplatin 130 mg/m² on day 1. With follow-up of median 16.6 months, median time to progression (TTP) was 7.6 months (95% confidence interval [CI], 6.7-8.5), and median overall survival was 19.7 months (95% CI, 14.8-23.6). Two patients (9%) achieved complete response and 6 patients (29%) showed partial response. In subgroup analysis with tissue specimens obtained from 17 patients, median TTP was longer among patients with the intestinal-type adenocarcinoma (n = 7), compared to those with the pancreatobiliary type (n = 10) (13.1 vs. 6.4 months, P = 0.038). The most common grade 3-4 adverse event was neutropenia (27%), and most events were mild. XELOX chemotherapy shows favorable efficacy with manageable toxicity for advanced intestinal-type ampullary adenocarcinoma.

Pharmacogenetic determinants associated with sunitinib-induced toxicity and ethnic difference in Korean metastatic renal cell carcinoma patients.

PURPOSE: The aim of this study was to investigate the pharmacogenetic determinants of sunitinib-related toxicity and ethnic difference in metastatic renal cell carcinoma (mRCC) among Korean patients. METHODS: A pharmacogenetic study was performed in 65 patients with mRCC treated with the standard schedule of sunitinib (50 mg orally once daily for 4 weeks-on/2 weeks-off). Detailed data regarding the toxicity of sunitinib, including thrombocytopenia, neutropenia, anemia, and hand-foot syndrome (HFS), were prospectively collected in a clinical trial program (n = 38) or standard oncology practice (n = 27). Total of 12 genetic polymorphisms in 8 candidate genes (CYP1A1, CYP3A5, ABCB1, ABCG2, PDGFRα, VEGFR2, RET, and FLT3) were analyzed for an association with treatment-related toxicity from sunitinib using Pearson χ (2) test. RESULTS: Common grade 3 or grade 4 treatment-related toxicities were thrombocytopenia (36.9 %, 24/65), neutropenia (18.4 %, 12/65), anemia (7.7 %, 5/65), and HFS (12.3 %, 8/65). Patients carrying an ABCG2 421 AA genotype developed significantly more grade 3 or grade 4 thrombocytopenia, neutropenia, and HFS adjusted for age, sex, and Eastern Cooperative Oncology Group performance status, and body surface area (odds ratio compared with AC/CC genotypes [OR] 9.90, P = 0.04, thrombocytopenia; OR 18.20, P = 0.02, neutropenia; and OR 28.46, P = 0.01, HFS). In addition, total and surface protein ABCG2 protein expression was decreased in ABCG2 421 AA mutant cells compared to wild type. CONCLUSION: Among 12 genetic polymorphisms, polymorphism in the ABCG2 421C>A gene may be mostly associated with the risk of sunitinib-related toxicity in mRCC patients. Considering the high frequency of 421C>A SNP in Asian, this may be related to differential toxicities among ethnic groups.

Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study.

BACKGROUND: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, anti-angiogenesis, and apoptosis. This phase II trial evaluated the efficacy and toxicity profile of conventional FOLFIRI chemotherapy plus simvastatin in metastatic colorectal cancer patients. METHODS: Patients received irinotecan 180 mg/m(2) as a 90-min infusion followed by leucovorin 200 mg/m(2) in a 2-h infusion, and then 5-FU 400 mg/m(2) bolus injection followed by 2,400 mg/m(2) as a 46-h continuous infusion. Treatment cycles were repeated every 2 weeks until documented disease progression, unacceptable toxicity, or patient's refusal. Simvastatin 40 mg tablet was given once daily per oral everyday during the period of chemotherapy without a rest. RESULTS: From October 2005 to June 2006, 49 patients were enrolled. The overall response rate (ORR) was 46.9% (95% CI, 31.0-58.8) by intent-to-treat analysis and 45.8% (95% CI, 33.3-62.8) by per-protocol analysis. There were one complete response (CR) and 22 partial responses (PRs). Both CR and PRs were confirmed at least 4 weeks later. The disease-control rate was 83.7% (95% CI, 73.4-94.0). The median follow-up duration was 25.6 months (range, 20.9-28.8 months). The median survival of all patients was 21.8 months (95% CI, 14.4, 29.2). The median TTP was 9.9 months (95% CI, 6.4, 13.3). No patients experienced additional adverse effect that was definitely caused by simvastatin drug therapy in this trial. CONCLUSION: The combination of simvastatin plus FOLFIRI was a feasible regimen with promising antitumor activity.

Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC.

Brain metastases from hepatocellular carcinoma are extremely rare. The objectives of the current study were to assess the natural history, outcome, and possible prognostic factors in patients with brain metastases from hepatocellular carcinoma. Between 1995 and 2006, 6,919 patients with hepatocellular carcinoma were treated at Yonsei University Health System. Of those, 62 (0.9%) had a diagnosis of brain metastasis. We carried out a retrospective review of these 62 patients and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 54 years. Forty-seven patients (76%) were male, and 53 patients had hepatitis B. Median time from diagnosis of hepatocellular carcinoma to brain metastasis was 18.2 months, and 5 patients had brain involvement as their initial presentation. Intracranial hemorrhage was frequently associated (54.8%) with brain metastasis. The most common presenting symptoms were motor weakness, mental change, and headache. Metastases were treated with whole-brain radiation therapy (WBRT) alone in 17 patients and gamma knife surgery alone in 10 patients. Six patients underwent surgical resection and 5 patients were treated with surgical resection followed by WBRT. Twenty-four patients (39%) received steroids only. Median survival after diagnosis of brain metastasis was 6.8 weeks (95% confidence interval: 3.8-9.8 weeks). Univariate analysis showed that treatment modality, number of brain lesions, alpha-fetoprotein, ECOG performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on survival. In multivariate analysis, treatment modality, number of brain lesions, and Child-Pugh classification were statistically significant prognostic factors for survival. The overall prognosis of patients with brain metastases from hepatocellular carcinoma is extremely poor. Nevertheless, some subsets of patients manifested the most favorable survival criteria (single brain metastasis and good liver function); thus, for at least these patients, treatment may result in an improved survival time.

Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer.

S-1 is a novel, oral fluoropyrimidine and a known radiosensitizer. We conducted a phase I trial to establish a schedule of S-1/irinotecan with standard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer. Our findings suggest that this new combination is feasible and well tolerable.