Efficacy of pamidronate in pediatric osteosarcoma patients with low bone mineral density

PURPOSE: Most surviving pediatric osteosarcoma patients experience osteoporosis, bone pain, and pathologic fracture during and after therapy. The aim of this study was to evaluate the efficacy and side effects of pamidronate therapy in these patients. METHODS: Nine osteosarcoma patients (12.8±1.6 years of age; 5 boys and 4 girls) who had a history of nontraumatic fracture or severe pain after completing chemotherapy were included. Intravenous pamidronate (1.5 mg/kg) was given every 6 weeks for 4 to 6 cycles. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry. Clinical outcomes including acute side effects were also evaluated. RESULTS: After pamidronate treatments, all patients experienced decreased pain. Seven of 9 patients could walk without a crutch. The BMD of lumbar spine was increased by 0.108±0.062 mg/cm2 after 8.4±1.0 months (n=8, P=0.017) and the mean z-score improved from -2.14±0.94 to -1.76±0.95 (P=0.161). Six patients (67%) had an acute-phase reaction, and 2 patients had symptomatic hypocalcemia. CONCLUSION: Pamidronate appears to be safe and effective for the treatment of osteosarcoma in children with low BMD and bone pain.

Aldehyde dehydrogenase is used by cancer cells for energy metabolism

We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced by ALDH may be a reliable energy source for ATP production in NSCLC. This study revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels, which efficiently induced cell death following cell cycle arrest.

Factors Affecting Survival in Patients Undergoing Palliative Spine Surgery for Metastatic Lung and Hepatocellular Cancer: Dose the Type of Surgery Influence the Surgical Results for Metastatic Spine Disease?

BACKGROUND: Surgical treatment for metastatic spine disease has been becoming more prominent with the help of technological advances and a few favorable reports on the surgery. In cases of this peculiar condition, it is necessary to establish the role of surgery and analyze the factors affecting survival. METHODS: From January 2011 to April 2015, 119 patients were surgically treated for metastatic spine lesions. To reduce the bias along the heterogeneous cancers, the primary cancer was confined to either the lung (n = 25) or the liver (n = 18). Forty-three patients (male, 32; female, 11; mean age, 57.5 years) who had undergone palliative surgery were enrolled in this study. Posterior decompression and fusion was performed in 30 patients (P group), and anteroposterior (AP) reconstruction was performed in 13 patients (AP group) for palliative surgery. Pre- and postoperative (3 months) pain (visual analogue scale, VAS), performance status (Karnofsky performance score), neurologic status (American Spinal Injury Association [ASIA] grade), and spinal instability neoplastic score (SINS) were compared. The survival period and related hazard factors were also assessed by Kaplan-Meier and Cox regression analysis. RESULTS: Most patients experienced improvements in pain and performance status (12.3% +/- 17.2%) at 3 months postoperatively. In terms of neurologic recovery, 9 patients (20.9%) graded ASIA D experienced neurological improvement to ASIA E while the remainder was status quo. In an analysis according to operation type, there was no significant difference in patient demographics. At 12 months postoperatively, cumulative survival rates were 31.5% and 38.7% for the P group and the AP group, respectively (p > 0.05). Survival was not affected by the pre- and postoperative pain scale, Tokuhashi score, neurologic status, SINS, or operation type. Preoperative Karnofsky performance score (hazard ratio, 0.93; 95% confidence interval [CI], 0.89 to 0.96) and improvement of performance status after surgery (hazard ratio, 0.95; 95% CI, 0.92 to 0.97) significantly affected survival after operation. CONCLUSIONS: There was no significant difference in surgical outcomes and survival rates between posterior and AP surgery for metastatic lesions resulting from lung and hepatocellular cancer. Preoperative Karnofsky score and improvement of performance status had a significant impact on the survival rate following surgical treatment for these metastatic spine lesions.

Bone mineral density change during adjuvant chemotherapy in pediatric osteosarcoma

PURPOSE: Osteoporosis is currently receiving particular attention as a sequela in survivors of childhood osteosarcoma. The aim of this study was to evaluate bone mineral density (BMD) changes during methotrexate-based chemotherapy in children and adolescents with osteosarcoma. METHODS: Nine patients with osteosarcoma were included in this retrospective study and compared with eight healthy controls. BMD of the lumbar spine and unaffected femur neck of patients was serially measured by dual-energy x-ray absorptiometry (DXA) before and just after chemotherapy and compared with controls. RESULTS: Four patients (44%) showed decreased lumbar spine BMD and seven patients (78%) showed decreased femur neck BMD, while all controls showed increased lumbar and femur BMD (P=0.024 and P=0.023). The femur neck BMD z-scores decreased from -0.49+/-1.14 to -1.63+/-1.50 (P=0.032). At the end of therapy, five patients (56%) showed femur neck BMD z-scores below -2.0. CONCLUSION: The bone metabolism is disturbed during therapy in children with osteosarcoma, resulting in a reduced BMD with respect to healthy controls. Since a reduced BMD predisposes to osteoporosis, specific attention and therapeutic interventions should be considered.

New Korean reference for birth weight by gestational age and sex: data from the Korean Statistical Information Service (2008-2012)

PURPOSE: To construct new Korean reference curves for birth weight by sex and gestational age using contemporary Korean birth weight data and to compare them with the Lubchenco and the 2010 United States (US) intrauterine growth curves. METHODS: Data of 2,336,727 newborns by the Korean Statistical Information Service (2008-2012) were used. Smoothed percentile curves were created by the Lambda Mu Sigma method using subsample of singleton. The new Korean reference curves were compared with the Lubchenco and the 2010 US intrauterine growth curves. RESULTS: Reference of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles birth weight by gestational age were made using 2,249,804 (male, 1,159,070) singleton newborns with gestational age 23-43 weeks. Separate birth weight curves were constructed for male and female. The Korean reference curves are similar to the 2010 US intrauterine growth curves. However, the cutoff values for small for gestational age (<10th percentile) of the new Korean curves differed from those of the Lubchenco curves for each gestational age. The Lubchenco curves underestimated the percentage of infants who were born small for gestational age. CONCLUSION: The new Korean reference curves for birth weight show a different pattern from the Lubchenco curves, which were made from white neonates more than 60 years ago. Further research on short-term and long-term health outcomes of small for gestational age babies based on the new Korean reference data is needed.

Age at menarche in the Korean female: secular trends and relationship to adulthood body mass index

PURPOSE: The objective of this study is to estimate the trend in age at menarche in the Korean female and evaluate the relationship between age at menarche and adult body mass index (BMI), which is a indicator of later-life health. METHODS: We conducted a cross-sectional analysis of a nationally representative sample (self-reported age at menarche and measured height and weight) of 11,065 females aged 15 and older. Data were obtained from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-2009). RESULTS: We found a statistically significant decline in age at menarche in successive birth groups, indicating a 0.726 year decrease per decade. The age at menarche in 1990-1994 year birth group was 12.60 years, which showed a significant decreased from 3.11 years in the 1980-1984 birth group. We also found a significant negative association between age at menarche and current BMI. A one-year decrease in age at menarche was associated with mean BMI increase of 0.109 kg/m2 (95% confidence interval [CI], 0.069 to 0.150) after adjustment for age. In multivariate logistic regression, the odds ratios of obesity in females with early menarche (<12 years) was 1.845 fold (95% CI, 1.441 to 2.361). CONCLUSION: We found that age at menarche is still falling in the Korean female. We also found that early menarche is a risk factor for obesity in adults.

Age at menarche in the Korean female: secular trends and relationship to adulthood body mass index

PURPOSE: The objective of this study is to estimate the trend in age at menarche in the Korean female and evaluate the relationship between age at menarche and adult body mass index (BMI), which is a indicator of later-life health. METHODS: We conducted a cross-sectional analysis of a nationally representative sample (self-reported age at menarche and measured height and weight) of 11,065 females aged 15 and older. Data were obtained from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-2009). RESULTS: We found a statistically significant decline in age at menarche in successive birth groups, indicating a 0.726 year decrease per decade. The age at menarche in 1990-1994 year birth group was 12.60 years, which showed a significant decreased from 3.11 years in the 1980-1984 birth group. We also found a significant negative association between age at menarche and current BMI. A one-year decrease in age at menarche was associated with mean BMI increase of 0.109 kg/m2 (95% confidence interval [CI], 0.069 to 0.150) after adjustment for age. In multivariate logistic regression, the odds ratios of obesity in females with early menarche (<12 years) was 1.845 fold (95% CI, 1.441 to 2.361). CONCLUSION: We found that age at menarche is still falling in the Korean female. We also found that early menarche is a risk factor for obesity in adults.