Design and characterization of an intracavitary ultrasound hyperthermia applicator for recurrent or residual lesions in the vaginal cuff

For evaluating the feasibility of treating recurrent lesions in the vaginal cuff by hyperthermia, a 2-element ultrasound applicator was designed, constructed and characterized. A half-cylindrical transducer ( d = 1 cm, length = 1 cm) was used to construct the 2-element ultrasound applicator. Each element of this applicator was operated at 1.5 MHz and characterized by measuring transducer efficiency and acoustic power distribution. Thermocouple probes were used to measure the temperature rise in the phantom. The element sizes used in this study were selected to be comparable to a high dose rate brachytherapy colpostat applicator. Each element was powered separately to achieve a desired temperature pattern in a target. The acoustic output power as a function of applied electric power of elements 1 and 2 were linear over this 1-40 W range and efficiencies were 32.2 &#45 3.4% and 46.2 &#45 0.8%, respectively. The temperature measurements in the phantom showed that a 6°C temperature rise was achieved 2 cm from the applicator surface. As a conclusion, the ability of the ultrasound colpostat applicator to be used for hyperthermia was demonstrated by measuring acoustic output power, ultrasound field distribution and temperature rise in the phantom. Based on the characteristics of this applicator, it has the potential to be useful for inducing hyperthermia to the vaginal cuff in the clinic.     

Comprehensive genomic profiling of metastatic collecting duct carcinoma,renal medullary carcinoma,and clear cell renal cell carcinoma

Introduction and ObjectiveUnlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.Material and MethodsDNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626). Comprehensive genomic profiling was performed, and Tumor mutational burden (TMB) and microsatellite instability (MSI) were calculated. We analyzed all classes of genomic alterations.ResultsmCDC had 1.7 versus 2.7 genomic alterations/tumor in mCCRCC ( = 0.04). Mutations in VHL (P < 0.0001) and TSC1 (P = 0.04) were more frequent in mCCRCC. SMARCB1 (P < 0.0001), NF2 (P = 0.0007), RB1 (P = 0.02) and RET (P = 0.0003) alterations were more frequent in mCDC versus mCCRCC. No VHL alterations in mRMC and mCDC were identified. SMARCB1 genomic alterations were significantly more frequent in mRMC than mCDC (P = 0.0002), but were the most common alterations in both subtypes. Mutations to EGFR, RET, NF2, and TSC2 were more frequently identified in mCDC versus mRMC. The median TMB and MSI-High status was low with <1% of mCCRC, mCDC, and mRMC having ≥ 20 mut/Mb.ConclusionGenomic alteration patterns in mCDC and mRMC differ significantly from mCCRCC. Targeted therapies for mCDC and mRMC appear limited with rare opportunities to target alterations in receptor tyrosine kinase and MTOR pathways. Similarly, TMB and absence of MSI-High status in mCDC and mRMC suggest resistance to immunotherapies.     

Evaluation of the angiographic outcomes after clipping of intracranial aneurysms: determination of predisposing factors for occurrence of aneurysm remnants

ABSTRACT

Objectives: Aneurysm remnants after microsurgical clipping have a risk of regrowth and rupture and have not been validated in the era of three-dimensional angiography. Therefore, this study aimed to evaluate the angiographic outcome using three-dimensional rotational images and determine the predictors for remnants after microsurgical clipping.

Methods: Between January 2014 and May 2017, 139 aneurysms in 106 patients who were treated with microsurgical clipping, were eligible for this study. For the determination of aneurysm remnants after microsurgical clipping, the angiographic outcomes were evaluated using follow-up digital subtraction angiography within 7 days for unruptured aneurysms or within 2 weeks for ruptured aneurysms. According to the Sindou classification, the aneurysm remnants were dichotomized, and subgroup analysis was performed to identify the predictors of aneurysm remnants after clipping with various imaging parameters and clinical information.

Results: The overall rate of aneurysm remnants was 29.5% (41/139), in which retreatments were needed in 6.5% (9/139). The neck size and maximum diameter of aneurysms were independent predisposing factors for the aneurysm remnants that need retreatment (OR: 2.30; p < 0.001; OR: 1.38; p < 0.001, respectively).

Conclusions: This study demonstrated a low incidence of aneurysm remnants after microsurgical clipping which need to retreatment. However, selective postoperative angiography could provide us clear information of surgical result and evidence for long-term follow-up for some aneurysms with larger neck size (>5.7 mm) and maximum diameter (>7.1 mm).     

A robust method for assessing chemically induced mutagenic effects in the oral cavity of transgenic Big Blue® rats

The Big Blue® (BB) in vivo mutation assay uses transgenic rodents to measure treatment‐induced mutations in virtually any tissue. The BB assay can be conducted in rats or mice and is ideal for investigating tissue‐specific mutagenic mode of action of tumor induction. Some tissues such as oral mucosa have not been thoroughly studied. Due to the small quantity and cartilaginous nature of oral cavity tissues, development of special prosection and DNA isolation methods was required to permit robust analysis of mutations in these tissues. Improved surgical methods permitted collection of adequate and reproducible quantities of tissue (～45 mg gingiva/buccal and ～30 mg gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform extraction, to yield sufficient quantities of DNA from these tissues. In preliminary optimization work, mutant frequency (MF) in tongue and gingiva was increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct mutagen, N‐ethyl‐N‐nitrosourea. The oral cavity carcinogen, 4‐nitroquinoline‐1‐oxide (4‐NQO; 10 ppm in drinking water; 28 days), was qualified as a positive control for mutagenesis in oral tissues since it caused significant increases in cII MFs in gingiva/palate (50.2‐fold) and gingiva/buccal tissues (21.3‐fold), but not in liver or bone marrow (0.9‐ and 1.4‐fold, respectively). These results are consistent with the observation that 4‐NQO primarily induces tumors in oral cavity. Results also demonstrate the utility of the BB rat mutation assay and optimized methods for investigation of oral cavity mutagenicity, and by extension, analysis of other small and cartilaginous tissues. Environ. Mol. Mutagen. 56:629–636, 2015. © 2015 Wiley Periodicals, Inc.     

Effect of soft tissue thickness over the posterior border of the vertebral body and disc space on cage placement during posterior lumbar interbody fusion: A cadaveric study

In the present study, we investigated whether there is a difference between visual depth (VD) and radiological image depth (RD) of cages (i.e., structural interbody support devices) placed in disc spaces during posterior lumbar interbody fusion and whether soft tissues covering the posterior border of the vertebral body and associated disc space are the cause of any observed differences. Using digital calipers, cages were inserted at a depth of 5 mm from the soft tissues covering the posterior border of the vertebral body and disc space under direct vision; this depth was defined as VD. After insertion, RD was measured in triplicate. The reliability of RD measurements was evaluated using an intraclass coefficient test. To identify the cause of differences between VD and RD, the thicknesses of soft tissues were measured microscopically. A total of 40 lumbar intervertebral disc spaces with cages were evaluated. The mean RD of cages was 3.12 mm, while the mean difference between the VD and RD of cages (DVRD) was 1.91 mm. On histological examination, the mean thickness of the soft tissue was 2.02 mm. Comparative analysis between histological values and DVRD showed no statistical difference (P = 1.14, 1.55, 0.06). There was a significant difference between VD and RD during cage placement, and soft tissue structure appeared to be responsible for the DVRD of inserted cages. Therefore, cages should be inserted deeper to account for differences between visual and radiological image depths. Clin. Anat. 25:1066–1073, 2012. © 2012 Wiley Periodicals, Inc.     

Serum growth arrest-specific protein 6 levels are elevated in adult-onset Still’s disease

We investigated the growth arrest-specific protein 6 in adult-onset Still’s disease. Serums were collected from 52 adult-onset Still’s disease patients with follow-up samples of 21 patients. The growth arrest-specific protein 6 levels in adult-onset Still’s disease were higher compared to those in the normal controls (25.37?±?7.71 vs. 19.86?±?5.01 ng/mL, p?<?0.001). However, growth arrest-specific protein 6 did not correlate with disease activity. Also, growth arrest-specific protein 6 was not decreased after activity was resolved in the follow-up. The growth arrest-specific protein 6 in adult-onset Still’s disease patients were higher than the normal controls. However, growth arrest-specific protein 6 was not correlated with disease activity.