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At least 19 records

Historical Changes in Histological Diagnosis of Lung Cancer

Background: Histological classification of lung cancer is essential for investigations of carcinogenesis and treatment selection. We examined the temporal changes of lung cancer histological subtypes. Methods: Lung cancer cases diagnosed in the Life Span Study cohort between 1958 and 1999 were collected from tumor registries (TR), mainly consisting of population-based cancer registries. A total of 1,025 cases were histologically reviewed according to the World Health Organization 2004 Classification by a panel of pathologists (PP). Sensitivity and specificity of diagnoses in TR were calculated, assuming that the diagnosis by PP was the gold standard. Results: Sensitivity and specificity were 0.91 and 0.92 for adenocarcinoma (AD), respectively, and 0.92 and 0.94, respectively, for squamous cell carcinoma (SQ). They were similar for AD and SQ throughout the observation period. For small cell carcinoma (SM), sensitivity was low until about 1980 (0.47 in 1958–1969, and 0.61 in 1970–1979) and then became higher thereafter (0.98 in 1980–1989, and 0.95 in 1990–1999), whereas specificity was high during the whole period (range 0.99 to 1.00). Among 45 cases that were not reported as SM in TR but diagnosed as SM by PP, 16 cases were recorded as undifferentiated carcinoma in TR. Conclusion: Diagnosis of AD and SQ of lung cancer were generally consistent between TR records and PP review, but SMs tended to be coded as other histological types until the 1970s.

60 APPLIED LIFE SCIENCES↗

Liver metastases of neuroendocrine tumors: is it possible to diagnose different histologic subtypes depending on multiphasic CT features?

Purpose: To assess and compare the multiphasic computed tomography (CT) features of neuroendocrine tumor (NET) liver metastases and to investigate the possibility to predict the histologic subtype of the primary tumor. Materials and methods: Between January 2013 and December 2017 patients with biopsy proven NET with at least one liver metastasis who underwent multiphasic CT were enrolled in this study. All cases were acquired using a standardized multiphasic liver CT protocol, arterial, portal, and hepatic venous phases were obtained. Images were retrospectively analyzed in consensus by two abdominal radiologists blinded to clinical data and histologic subtype. The size, number, and location of lesions were noted. Enhancement patterns of each lesion on arterial, portal, and hepatic venous phases were assessed. For quantitative analysis, CT attenuation of tumors, liver parenchyma, and aorta were measured using a circular region of interest (ROI) on arterial, portal, and hepatic venous phases for reflecting the blood supply of the tumor. Tumor-to-aorta and tumor-to-liver ratio were calculated in all three phases. Differences between subtypes of NET liver metastases were studied using ROC analysis of clustered data. Results: A total of 255 neuroendocrine tumor liver metastases divided into 101 (39.6%) pancreatic, 60 (23.5%) gastroenteric and 94 (36.8%) lung NET liver metastases were analyzed. Contrast enhancement of lesions was homogeneous in 78% of patients (n = 199), which was significantly more frequent in patients with pancreatic group than in those with gastroenteric origin (n = 90, 89.1% vs. n = 28, 46.7%; p < 0.001). Gastroenteric NET metastases frequently showed heterogeneous enhancement, which was significantly higher than in the other two groups (50% vs. 3% and 2%). With respect to the location of the primary tumor, the difference in enhancement patterns of the liver lesions was statistically significant (p < 0.001). Pancreatic NET metastases were mostly hyperdense on arterial images and isodense on portal and hepatic venous phase images (79.2%, n = 80). Gastroenteric NET metastases were mostly hyperdense on arterial phase images and hypodense on portal and hepatic venous phase images (n = 28, 46.7%). The most frequent pattern for lung NET metastases was hypoattenuation on all three phase images (n = 44, 46.8%). ROC analysis of clustered data revealed statistically significant differences between pancreatic NET liver metastases, gastroenteric NET liver metastases, and lung NET liver metastases in terms of tumor-to-aorta (T–A) ratio and tumor-to-liver (T–L) ratio (p < 0.001). Conclusion: We observed statistically significant differences in multiphasic CT features (enhancement pattern, T–A ratio, and T–L ratio) between histologic subtypes of NET liver metastases. As the difference in histological subtypes of NET liver metastases results in a different prognosis and different management strategy, these CT features might help to identify the primary tumor when it is not known to ensure accurate tumor staging and to provide optimal treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies

This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal posture.

Theriot, C. A.↗

Texture analysis of small renal cell carcinomas at MDCT for predicting relevant histologic and protein biomarkers

Purpose: To assess CT texture features of small renal cell carcinomas (≤ 4cm) for association with key pathologic features including protein biomarkers. Methods: Quantitative CT texture analysis (CTTA) of small renal cancers (≤ 4cm) was performed on non-contrast and portal venous phase abdominal MDCT scans with an ROI drawn at the largest cross-sectional diameter of the tumor using commercially available software. Texture parameters including mean pixel attenuation, the standard deviation (SD) of the pixel distribution histogram, entropy, the mean of positive pixels, the skewness (i.e., asymmetry) of the pixel histogram, kurtosis (i.e., peakness) of the pixel histogram, and the percentage of positive pixels were correlated with pathologic data from surgical resection, including histology and nuclear grade, as well as microarray analysis in a subset (n = 40) including Ki67 index, CRP, and neovascularization (CD105/CD31). Results: Portal venous phase images were available in 249 patients (105 women, 144 men; mean age, 56.7 years) with tumors ≤ 4cm (mean, median, range, ± SD; 2.66, 2.60, 0.3–4.0 ± 0.85 cm). CT texture features of standard deviation, mean of the positive pixels, and entropy of the pixel histogram were significantly associated with histologic cell type (clear vs. non-clear; p < 0.001). Entropy and mean of the positive pixels also showed an association with nuclear grade, although not statistically significant. In the microarray analysis subset, kurtosis of the pixel histogram was associated with CD105/CD31 (p = 0.05). SD also showed some association with CD 105 positivity (p = 0.02) and CAIX expression (p = 0.01). Non-contrast CT images were available in 174 patients (72 women, 102 men; mean age, 57.5 years). Although the association with histology was not as strong as on the portal venous phase, in the subset of patients with microarray data, SD was found to correlate with CRP (p = 0.08), kurtosis with CRP (p = 0.004), CD105/CD31 (p = 0.002), and with Ki 67 index (p < 0.001). Conclusion: CT texture features were significantly associated with important histopathologic features in small renal cancers. These non-invasive measures can be performed retrospectively and may provide useful information when determining follow-up and treatment of small renal cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Histological preparation of developing vestibular otoconia for scanning electron microscopy

The unique nature of vestibular otoconia as calcium carbonate biominerals makes them particularly susceptible to chemical deformation during histological processing. We fixed and stored otoconia from all three otolith endorgans of embryonic, hatchling and adult Japanese quail in glutaraldehyde containing either phosphate or non-phosphate buffers for varying lengths of time and processed them for scanning electron microscopy. Otoconia from all age groups and otolith endorgans processed in 0.1 M phosphate buffer (pH 7.4) showed abnormal surface morphology when compared to acetone fixed controls. Otoconia processed in 0.1 M sodium cacodylate or HEPES buffered artificial endolymph (pH 7.4) showed normal morphology that was similar to controls. The degree of otoconial deformation was directly related to the time exposed to phosphate buffer. Short duration exposure produced particulate deformations while longer exposures resulted in fused otoconia that formed solid sheets. Otoconial surface deformation and fusing was independent of the glutaraldehyde component of the histological processing. These findings should help vestibular researchers to develop appropriate histological processing protocols in future studies of otoconia.

Non-NASA Center↗

Histological and Transcriptomic Analysis of Spaceflight-Induced Ocular Changes in the Mouse Retina

Anatomical changes have been observed in astronauts’ eyes after long duration spaceflight missions. These alterations can lead to visual impairment which in part constitutes the spaceflight-associated neuroocular syndrome (SANS), one of the top risk priorities for deep space missions. The HRP Systems Biology (SysBio) Translation Project will apply systems biology approaches utilizing current human physiological spaceflight data, molecular results from rodents, and future research with a multi-level, multi-system, and multi-species perspective to augment the existing research plan to resolve the SANS risk. Not much is known about SANS at the cellular and molecular level, but studies in mice and rats have recently begun to determine how spaceflight might affect the biology of the eye. Preliminary studies of mice that flew on the Space Shuttle, and more recently the International Space Station (ISS), have shown changes in retinal physiology as assessed by histology and gene expression analysis. The study presented here obtained samples from the CASIS sponsored Rodent Research 8 Experiment delivered to the ISS by SpaceX CRS-16 on 12/08/2018. Female BALB/cAnNTac mice flew on the ISS for 45 days, while ground controls were housed in a standard vivarium or animal enclosure module. Sacrifice and sample acquisition occurred once mice returned to Earth, possibly allowing for readaptation affecting retinal homeostasis. We applied standard transcriptomic (RNAseq) and histological approaches to characterize genes and pathways in the mouse retina affected by spaceflight or age. The differentially expressed gene (DEG) data was analyzed using Galaxy (GeneLab) and Ingenuity Pathway Analysis. Significant DEGs between flight and ground samples were relatively few but biologically meaningful. Pathways identified related to neuronal differentiation, cellular transport/movement, and wound healing. Age effects were detected between the young (10–12 weeks) and old (32 weeks) groups and between the baseline and end of experiment (~46 days). The biological relevance of specific DEGs were confirmed through immunohistochemical evaluation using fixed histological sections of the eye from four flight group mice and four habitat control mice. Staining was performed specific for synaptophysin, glial fibrillary acidic protein (GFAP), and neurofilament in the retinal periphery, equator, and peripapillary regions. For synaptophysin staining, the innerplexiform and outerplexiform layers were scored; for GFAP staining, Mueller cells and perivascular astrocytes were scored. Results show flight samples typically had more staining of GFAP and neurofilament while, conversely, the habitat control group had more staining of synaptophysin.

C. Perez↗

Data augmentation and multimodal learning for predicting drug response in patient-derived xenografts from gene expressions and histology images

Patient-derived xenografts (PDXs) are an appealing platform for preclinical drug studies. A primary challenge in modeling drug response prediction (DRP) with PDXs and neural networks (NNs) is the limited number of drug response samples. We investigate multimodal neural network (MM-Net) and data augmentation for DRP in PDXs. The MM-Net learns to predict response using drug descriptors, gene expressions (GE), and histology whole-slide images (WSIs). We explore whether combining WSIs with GE improves predictions as compared with models that use GE alone. We propose two data augmentation methods which allow us training multimodal and unimodal NNs without changing architectures with a single larger dataset: 1) combine single-drug and drug-pair treatments by homogenizing drug representations, and 2) augment drug-pairs which doubles the sample size of all drug-pair samples. Unimodal NNs which use GE are compared to assess the contribution of data augmentation. The NN that uses the original and the augmented drug-pair treatments as well as single-drug treatments outperforms NNs that ignore either the augmented drug-pairs or the single-drug treatments. In assessing the multimodal learning based on the MCC metric, MM-Net outperforms all the baselines. Our results show that data augmentation and integration of histology images with GE can improve prediction performance of drug response in PDXs.

60 APPLIED LIFE SCIENCES↗

The effect of nonablative laser energy on joint capsular properties. An in vitro histologic and biochemical study using a rabbit model

The purpose of this study was to evaluate the effect of laser energy at nonablative levels on joint capsular histologic and biochemical properties in an in vitro rabbit model. The medial and lateral portions of the femoropatellar joint capsule from both stifles of 12 mature New Zealand White rabbits were used. Specimens were divided into three treatment groups (5 watts, 10 watts, and 15 watt) and one control group using a randomized block design. Specimens were placed in a 37 degrees bath of lactated Ringer's solution and laser energy was applied using a holmium:yttrium-aluminum-garnet laser in four transverse passes across the tissue at a velocity of 2 mm/sec with the handpiece set 1.5 mm from the synovial surface. Histologic analysis revealed thermal alteration of collagen (fusion) and fibroblasts (pyknosis) at all energy densities, with higher laser energy causing significantly greater morphologic changes over a larger area (P < 0.05). Application of laser energy did not significantly alter the biochemical parameters evaluated, including type I collagen content and nonreducible crosslinks (P > 0.05). This study demonstrated that nonablative laser energy caused significant thermal damage to the joint capsular tissue in an energy-dependent fashion, but type I collagen content and nonreducible crosslinks (P > 0.05). This study demonstrated that nonablative laser energy caused significant thermal damage to the joint capsular tissue in an energy-dependent fashion, but type I Collagen content and nonreducible corsslinks were not significantly altered.

NASA Discipline Musculoskeletal↗

Method of and Apparatus for Histological Human Tissue Characterization Using Ultrasound

A method and apparatus for determining important histological characteristics of tissue, including a determination of the tissue's health is discussed. Electrical pulses are converted into meaningful numerical representations through the use of Fourier Transforms. These numerical representations are then used to determine important histological characteristics of tissue. This novel invention does not require rectification and thus provides for detailed information from the ultrasonic scan.

Yost, William T.↗

Method of and Apparatus for Histological Human Tissue Characterization Using Ultrasound

A method and apparatus for determining important histological characteristics of tissue, including a determination of the tissue's health. Electrical pulses are converted into meaningful numerical representations through the use of Fourier Transforms. These numerical representations are then used to determine important histological characteristics of tissue. This novel invention does not require rectification and thus provides for detailed information from the ultrasonic scan.

Yost, William T.↗

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

NASA Discipline Musculoskeletal↗

Impact of Simulated Galactic Cosmic Radiation and Hindlimb Unloading on the Mouse Adrenal Gland Morphology and Histology

Stress related impact of Galactic Cosmic Radiation (GCR) combined with microgravity in space are concerns for astronauts going beyond the Van Allen belts on their way to the Moon and Mars. The adrenal gland is the central endocrine tissue involved in stress management, adrenal hormones regulate the immune system, cellular and tissue metabolism, and glucose and sodium balances. Adult (6 m old) female (n=18) and male (n=18) C57BL/6J mice were divided evenly into 6 treatment groups (control, hindlimb unloading (HU), irradiated (IR), HU+IR, group house control, and group house IR). Adrenals were dissected and fixed for 24 h in 4% paraformaldehyde, followed by transfer to 70% EtOH, and shipment to KUMC. Adrenals were then embedded in paraffin and serial sectioned and 4 central sections from each were stained with H&E, prior to imaging on a Nikon 80i microscope. Whole adrenal cross section area, medullary area, and cortex area were determined. General adrenal gland morphology and histology did not appear to be affected by hindlimb unloading or GCR exposure. Total cross-sectional area, medullary region, and cortex of the adrenal were not different across treatment groups. Male adrenal cross-sectional areas are half the size of the female adrenals, due to a difference in cortex area. In conclusion, simulated microgravity and GCR did not dramatically affect the adrenal gland histology or size. Support from Accelerate Cancer Education Internship Program (KUCC) and KINBRE Summer Scholars Program (KUMC) and NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028

radiation↗

Histological Findings in Wild Rodents of the Great Basin

In the western United States, significant environmental change is expected through the combined effects of climate change, tree mortality, drought, and invasive species. Wild animals can be used as indicators of threats to populations and even entire communities by looking for histopathological changes in their tissues. This method may identify threats to wild populations quickly and more accurately than waiting to observe population declines; however, baseline data are needed for comparisons. In this work, rodents are surveyed at 5 sites in the Great Basin to record histopathological changes. Additionally, one site is next to a copper mine that was in operation for nearly 100 years. This site is compared to the other more pristine sites. Liver, lung, heart, and kidney tissues of 143 rodents from 10 species were processed and examined using standard histological methods. Thirty percent of rodents had histopathological changes. The most common histopathological changes were extramedullary hematopoiesis (11.9%), hyperplastic BALT (6.3%), and pyelitis (4.9%). Two pathogens were found: the nematode Capillaria hepatica (0.7%) and the fungus Emmonsia crescens (2.8%). The most common rodent captured, Peromyscus maniculatus (n = 116), was used to determine whether sex and mass predict histopathological changes. Body mass, not sex, was the best predictor, suggesting that heavier, older individuals should be selectively sampled if the goal is to assess potential threats to rodent populations. Data such as these can be compared to future data to assess populations and communities for effects of environmental change.

59 BASIC BIOLOGICAL SCIENCES↗

Histologic Analysis with the Newly Designed Exoskeleton Seal{sup ®} Stent-Graft in the Porcine Abdominal Aorta

Purpose: To investigate the technical feasibility of a novel exoskeleton Seal{sup ®} stent-graft and analyze early histologic changes in the porcine abdominal aorta. Materials and Methods: Six pigs received an abdominal stent-graft (Group I), and six received an iliac branch stent-graft (Group II). Groups were subdivided as follows: Group Ia, which received three bifurcated main-body stent-grafts; Group Ib, which received three bifurcated main-body stent-grafts with both iliac graft-stents; Group IIa, which received three simple uni-iliac tapered stent-grafts; and Group IIb, which received three uni-iliac tapered tapered stent-grafts with right straight limb and left branched limb. Statistical analyses were performed with the Wilcoxon signed-rank test and mixed-model regression analysis. Results: The primary technical success rate (< 24 h) was 83% because of two acute thromboses in the lumen of the stented abdominal aorta immediately after stent-graft placement. At 4 weeks, late thrombosis occurred in two pigs. Higher mean neointimal hyperplasia areas (23.5% vs. 16.2%; P = .047), neointimal hyperplasia thicknesses (545.5 μm vs. 422.2 μm; P = .001), and degrees of collagen deposition (2.71 vs. 2.33; P = .002) were observed at the bare-metal stent-graft compared with the proximal exoskeleton portion of the stent-graft, with no significant differences between the patent and occluded groups or among the four types of stent-grafts. Conclusions: The exoskeleton stent-graft demonstrates 66% of patency rate during 1-month follow-up due to four cases of thromboses; however, the endothelialization on the junction of proximal graft showed no significant differences between the patent and occluded groups. Further studies should investigate long-term outcomes with prolonged neointimal hyperplasia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗