Feasibility of SBRT for hepatocellular carcinoma in Brazil — a prospective pilot study

BACKGROUND: The aim of the study was to evaluate the feasibility and safety of stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma in Brazil. SBRT is an evolving treatment in HCC patients not candidates to other local therapies. Its adoption in clinical practice has been heterogeneous, with lack of data on its generalizability in the Brazilian population. MATERIALS AND METHODS: We conducted a prospective pilot study involving HCC patients after failure or ineligibility for transarterial chemoembolization. Patients received SBRT 30 to 50 Gy in 5 fractions using an isotoxic prescription approach. This study is registered at clinicaltrials.gov NCT02221778. RESULTS: From Nov 2014 through Aug 2019, 26 patients received SBRT with 40 Gy median dose. Underlying liver disease was hepatitis C, hepatitis B and alcohol-related in, respectively, 50%, 23% and 19% of patients. Median lesion size was 3.8 cm (range, 1.5–10 cm), and 46% had multiple lesions. Thirty-two percent had tumor vascular thrombosis; median pretreatment alpha-fetoprotein (AFP) was 171.7 ng/mL (range, 4.2–5,494 ng/mL). 1y-local progression-free survival (PFS) was 86% (95% CI: 61% to 95%), with higher local control in doses ≥ 45Gy (p = 0.037; HR = 0.12). 1y-liver PFS, distant PFS and OS were, respectively, 52%, 77% and 79%. Objective response was seen in 89% of patients, with 3 months post-SBRT median AFP of 12 ng/mL (2.4–637 ng/mL). There were no grade 3 or 4 clinical toxicities. Grade 3 or 4 laboratory toxicities occurred in 27% of patients. CONCLUSION: SBRT is feasible and safe in patients unresponsive or ineligible for TACE in Brazil. Our study suggests doses > 45Gy yields better local control

The skin-to-calyx distance measured by renal ct scan and ultrasound

PurposeWe developed a stereotactic device to guide the puncture for percutaneous nephrolithotripsy, which uses the distance from the target calyx to its perpendicular point on skin (SCD) to calculate the needle´s entry angle. This study seeks to validate the use of measurements obtained by ultrasound (US) and computerized tomography (CT) for needle´s entry angle calculation and to study factors that may interfere in this procedure.Materials and MethodsHeight, weight, abdominal circumference, CT of the urinary tract in dorsal decubitus (DD) and ventral decubitus (VD), and US of the kidneys in VD were obtained from thirty-five renal calculi patients. SCD obtained were compared and correlated with body-mass index (BMI).ResultsBMI was 28.66 ± 4.6 Kg/m2. SCD on CT in DD was 8.40 ± 2.06cm, in VD was 8.32 ± 1.95cm, in US was 6.74 ± 1.68cm. SCD measured by US and CT were statistically different (p < 0.001), whereas between CT in DD and VD were not. SCD of the lower calyx presented moderate correlation with BMI.ConclusionSCD obtained by CT in ventral and dorsal decubitus may be used for calculation of the needle´s entry angle. SCD obtained by US cannot be used. A rule for the correlation between BMI and the SCD could not be determined

Arc-based directed energy deposited Inconel 718: role of heat treatments on high-temperature tensile behavior

This study evaluated the effect of dedicated heat treatments (1050°C, 1100°C, 1142°C, and 1185°C/2 h + double-aging) on the uniaxial tensile properties at elevated temperature (650°C) of Inconel® 718 fabricated via arc plasma directed energy deposition. They enabled to meet, for the first time, the AMS 5662 requirements at elevated temperature. Tensile tests exhibited ductile strain–stress curves. The 1100°C/2 h + double-aging showed the best performance (YS0.2%, UTS, and elongation of 967 MPa, 1126 MPa, and 18.7%, respectively). Additionally, vertical specimens evidenced dynamic strain aging, although no brittle-like features were observed

Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma

Abstract Background DNA methylation in miRNA genes has been reported as a mechanism that may cause dysregulation of mature miRNAs and consequently impact the gene expression. This mechanism is largely unstudied in papillary thyroid carcinomas (PTC). Methods To identify differentially methylated miRNA-encoding genes, we performed global methylation analysis (Illumina 450 K), integrative analysis (TCGA database), data confirmation (pyrosequencing and RT-qPCR), and functional assays. Results Methylation analysis revealed 27 differentially methylated miRNA genes. The integrative analyses pointed out miR-21 and miR-146b as potentially regulated by methylation (hypomethylation and increased expression). DNA methylation and expression patterns of miR-21 and miR-146b were confirmed as altered, as well as seven of 452 mRNAs targets were down-expressed. The combined methylation and expression levels of miR-21 and miR-146b showed potential to discriminate malignant from benign lesions (91–96% sensitivity and 96–97% specificity). An increased expression of miR-146b due to methylation loss was detected in the TPC1 cell line. The miRNA mimic transfection highlighted putative target mRNAs. Conclusions The increased expression of miR-21 and miR-146b due to loss of DNA methylation in PTC resulted in the disruption of the transcription machinery and biological pathways. These miRNAs are potential diagnostic biomarkers, and these findings provide support for future development of targeted therapies