Efficacy, toxicities, and prognostic factors of stereotactic body radiotherapy for unresectable liver metastases.

INTRODUCTION: This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery. METHODS: This study included 31 consecutive patients with unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival. RESULTS: Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer). CONCLUSION: Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.

Nonlinear association between bone mineral density and all-cause mortality: the Dong-gu study.

There was a U-shaped association between hip BMD and all-cause mortality, with the lowest mortality in the 90th percentile in males. However, there was an inverse linear relationship in females. In contrast, the association between lumbar spine BMD and mortality was less evident in males, with no association in females. INTRODUCTION: Bone mineral density (BMD) is reported inversely associated with mortality. Although some previous studies provided evidence for nonlinear associations, these were not adequately assessed in most previous works. METHODS: We evaluated the nonlinear relationship between BMD and mortality in Asians. Our study involved 8629 participants in the Dong-gu study from 2007 to 2010. Cox proportional hazard regression was used to calculate hazard ratios (HRs) according to BMD categories after adjusting for potential confounders. During a follow-up of 6.7 ± 1.4 years, 712 participants died. RESULTS: There was a U-shaped association between hip BMD and all-cause mortality, with the lowest mortality in the 90th percentile in males. However, there was an inverse linear relationship in females. In males, compared with the 75th to 95th percentile group, the < 2.5th percentile group had a 3.89 (95% CI 2.41-6.28)-fold higher risk and the 2.5th to 5th percentile group had a 2.51 (95% CI 1.25-5.04)-fold higher risk. The HR was 2.51 (95% CI 1.25, 5.04) in the > 97.5th percentile group. In females, compared with that in the 75th to 95th percentile group, the HR was 2.33 (95% CI 1.24, 4.39) in the < 2.5th percentile group. In contrast, the association between lumbar spine BMD and mortality was less evident in males, with no association in females. CONCLUSION: In conclusion, this study shows that the association between BMD and mortality varies by gender and that high and low BMD are predictors of all-cause mortality in males.

A New Experiment for Investigating Evaporation and Condensation of Cryogenic Propellants.

Passive and active technologies have been used to control propellant boil-off, but the current state of understanding of cryogenic evaporation and condensation in microgravity is insufficient for designing large cryogenic depots critical to the long-term space exploration missions. One of the key factors limiting the ability to design such systems is the uncertainty in the accommodation coefficients (evaporation and condensation), which are inputs for kinetic modeling of phase change. A novel, combined experimental and computational approach is being used to determine the accommodation coefficients for liquid hydrogen and liquid methane. The experimental effort utilizes the Neutron Imaging Facility located at the National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland to image evaporation and condensation of hydrogenated propellants inside of metallic containers. The computational effort includes numerical solution of a model for phase change in the contact line and thin film regions as well as an CFD effort for determining the appropriate thermal boundary conditions for the numerical solution of the evaporating and condensing liquid. Using all three methods, there is the possibility of extracting the accommodation coefficients from the experimental observations. The experiments are the first known observation of a liquid hydrogen menisci condensing and evaporating inside aluminum and stainless steel cylinders. The experimental technique, complimentary computational thermal model and meniscus shape determination are reported. The computational thermal model has been shown to accurately track the transient thermal response of the test cells. The meniscus shape determination suggests the presence of a finite contact angle, albeit very small, between liquid hydrogen and aluminum oxide.

Efficacy of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic or advanced colorectal carcinoma--a dual-centre phase II study: the MAC-6.

AIMS: A phase II trial was initiated to evaluate the efficacy and toxicity of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients received a combination of CPT-11 plus capecitabine. CPT-11 was infused intravenously on day 1 every 2 weeks and oral capecitabine was taken twice daily for 5 days every 7 days. Efficacy and toxicities were assessed. RESULTS: Between 2004 and 2005, 43 patients were enrolled. The overall response rate was 51.35%. With a median follow-up of 13 months, the median time to progression was 10 months (95% confidence interval 7.6-12.3 months); the median survival was 15 months (95% confidence interval 13.9-16.9 months). The most common grade 3 haematological and non-haematological toxicities were neutropenia (5.4%), diarrhoea (8.1%) and hand-foot syndrome (2.7%). CONCLUSIONS: CPT-11 plus capecitabine with a 14 day cycle showed a comparable response with international phase II data with a 3 weekly regimen and was well tolerated as a first-line palliative chemotherapy in patients with metastatic colorectal cancer. The data should be interpreted with caution due to the limited sample size and should be further confirmed by a phase III randomised trial.

Dosimetric perturbations of linear array of beta-emitter seeds and metallic stent in intravascular brachytherapy.

The radiation treatment with catheter-based beta-emitter sources is under clinical trials to prevent restenosis following interventional coronary procedures. There are still large uncertainties in the dose calculation due to the complicated treatment geometry. We present the Monte Carlo simulations to account for the dosimetric perturbations due to neighboring trained seeds, proximal/distal gold markers, and a stainless steel stent. A catheter-based beta-emitter system is modeled using the Monte Carlo code, MCNP4B. Dose distributions and dose rates are calculated in voxels (0.64x0.64x0.5 mm3) around the long cylindrical trains of 90Sr/Y source with and without the stent (at 1.92 mm from the source axis). For the total activity of 70 mCi (2.59x10(9) Bq), the dose around most of the source length (except for edge seeds and gold markers) varies from 40 to 0.23 cGy/s as the radial distance from the source axis (r) increases from 0.64 to 6.4 mm. At the prescription range of r = 1.5-4.0 mm, the dose gradient is very steep and the contribution of neighboring seeds to the dose is significant. The dose enhancement due to neighboring seeds (the so-called "train effect") varies from 9% to 64% as r increases from 0.64 to 5.2 mm. The doses at r = 2 mm from the last edge seed and the gold marker are about 80% and 40% of that of the nonedge seed (8.7 cGy/s), respectively. The dose enhancement due to the secondary electrons and the primary electrons scattered with the stent is shown to be about 9.3% in the voxel including the stent. However, as r increases beyond the stent (r = 2.0-6.4 mm), the dose is slightly reduced by 4%-12%, compared to that without the stent.

Pentoxifylline potentiates nitric oxide production in interleukin-1beta-stimulated vascular smooth muscle cells through cyclic AMP-dependent protein kinase A pathway.

In the present study, we observed that pentoxifylline (PTX) significantly augmented the nitric oxide (NO) production and the iNOS gene expression by interleukin-1beta (IL-1beta)-stimulated vascular smooth muscle cells (VSMCs). The enhancing effects of PTX on the IL-1beta-induced NO production was associated with an increased intracellular cyclic AMP (cAMP) levels, and the synergistic effects of PTX on the IL-1beta-induced NO production was blocked by cAMP-dependent protein kinase A (PKA) inhibitors. PKA inhibitors, KT5720 and H89, markedly decreased the augmented expression of iNOS gene whereas ODQ, a soluble guanylate cyclase inhibitor, did not affect the enhancing effect. In addition, the pretreatment with KT5720 or H89 abolished the increased translocation of the p65 subunit of NF-kappaB into the nucleus by PTX in the IL-1beta-stimulated VSMCs. These results suggest that enhancing effects of PTX on the iNOS gene expression in the IL-1beta-stimulated VSMCs is mediated predominantly through the activation of NF-kappaB via cAMP-dependent PKA pathway.

Genetic analysis of regions of the Lactococcus lactis subsp. lactis plasmid pRS01 involved in conjugative transfer.

The genes responsible for conjugative transfer of the 48.4-kb Lactococcus lactis subsp. lactis ML3 plasmid pRS01 were localized by insertional mutagenesis. Integration of the IS946-containing plasmid pTRK28 into pRS01 generated a pool of stable cointegrates, including a number of plasmids altered in conjugative proficiency. Mapping of pTRK28 insertions and phenotypic analysis of cointegrate plasmids identified four distinct regions (Tra1, Tra2, Tra3, and Tra4) involved in pRS01 conjugative transfer. Tra3 corresponds closely to a region previously identified (D. G. Anderson and L. L. McKay, J. Bacteriol. 158:954-962, 1984). Another region (Tra4) was localized within an inversion sequence shown to correlate with a cell aggregation phenotype. Tra1 and Tra2, two previously unidentified regions, were located at a distance of 9 kb from Tra3. When provided in trans, a cloned portion of the Tra3 region complemented Tra3 mutants.