Radiation Segmentectomy

Radiation segmentectomy is an yttrium-90 transarterial radioembolization treatment where a high radiation dose is administered to a small volume of liver to achieve a high tumoricidal dose to a target with anatomic surgical precision while sparing surrounding parenchyma. This therapeutic modality is often used to treat hepatocellular carcinoma, and recent studies have demonstrated that radiation segmentectomy is an effective treatment as a neoadjuvant to transplant, resection, or as a standalone treatment. This article provides a review of radiation segmentectomy, indications for treatment, recent outcome data, and guidelines for postprocedural management.

Adult fibroblasts retain organ-specific transcriptomic identity

Organ fibroblasts are essential components of homeostatic and diseased tissues. They participate in sculpting the extracellular matrix, sensing the microenvironment and communicating with other resident cells. Recent studies have revealed transcriptomic heterogeneity among fibroblasts within and between organs. To dissect the basis of interorgan heterogeneity, we compare the gene expression of fibroblasts from different tissues (tail, skin, lung, liver, heart, kidney, gonads) and show that they display distinct positional and organ-specific transcriptome signatures that reflect their embryonic origins. We demonstrate that fibroblasts′ expression of genes typically attributed to the surrounding parenchyma is established in embryonic development and largely maintained in culture, bioengineered tissues, and ectopic transplants. Targeted knockdown of key organ-specific transcription factors affects fibroblasts functions, with modulation of genes related to fibrosis and inflammation. Our data open novel opportunities for the treatment of fibrotic diseases in a more precise, organ-specific manner.

The Impact of Fixation on the Detection of Oligodendrocyte Precursor Cell Morphology and Vascular Associations

Oligodendrocyte precursor cells (OPCs) display numerous protrusions that extend into the surrounding parenchyma in the brain. Depending on the preparation of the tissue analyzed, these protrusions are more or less visible. We applied six different fixation methods and compared the effect of prolonged and stronger fixation on fluorescence intensity of platelet-derived growth factor receptor alpha, a surface marker of OPCs. Importantly, the fluorescence signal is mostly lost on protrusions as compared to the cell body, which has to be considered for specific analyses. Additionally, we show numerous contacts established between OPCs and the brain vasculature, which will contribute to the understanding of the interactions between these two elements.

Histological Features of Sporadic and Familial Testicular Germ Cell Tumors Compared and Analysis of Age-Related Changes of Histology

This study aimed to compare histological features of familial and sporadic testicular germ cell tumors (TGCTs) and surrounding parenchyma, since discriminating features might be etiologically relevant and clinically useful. The study of parenchyma was prompted by reports claiming a higher prevalence of testicular microlithiasis in familial cases. Histological features of TGCTs and surrounding parenchyma of 296 sporadic and 305 familial cases were compared. For each case, one representative hematoxylin and eosin-stained slide was available. Slides were independently scored by two expert pathologists using a semi-quantitative data abstract. Discrepancies were resolved by consensus. A logistic regression model was used to assess the ability to discriminate between sporadic and familial GCT. The histological composition of a tumor, amount of lymphocytic infiltration, amount of germ cell neoplasia in situ (GCNIS), and presence of testicular microlithiasis (TM) did not discriminate between sporadic and familial GCT (area under the curve 0.56, 95%CI 0.51–0.61). Novel observations included increasing lymphocytic infiltration and decreasing GCNIS and TM with increasing age at diagnosis. The presence of tubules with infiltrating lymphocytes was mainly associated with pure seminomas and nonseminomas with a seminoma component. Among seminomas, tubules with infiltrating lymphocytes decreased with increasing age. No discernable differences between sporadic and familial TGCTs were found. The age-related changes in the tumors and surrounding parenchyma in these groups combined are consistent with a host response building up over time predominantly affecting seminomas, the seminoma-component of nonseminomas and GCNIS. TM may gradually dissolve with age. Our hypothesis that histological differences between sporadic and familial TGCT might identify genetically distinct disease subsets was not supported.

EGFRvIII uses intrinsic and extrinsic mechanisms to reduce glioma adhesion and increase migration

ABSTRACTA lack of biological markers has limited our ability to identify the invasive cells responsible for glioblastoma multiforme (GBM). To become migratory and invasive, cells must downregulate matrix adhesions, which could be a physical marker of invasive potential. We engineered murine astrocytes with common GBM mutations, e.g. Ink4a (Ink) or PTEN deletion and expressing a constitutively active EGF receptor truncation (EGFRvIII), to elucidate their effect on adhesion. While loss of Ink or PTEN did not affect adhesion, counterparts expressing EGFRvIII were significantly less adhesive. EGFRvIII reduced focal adhesion size and number, and these cells – with more labile adhesions – displayed enhanced migration. Regulation appears to depend not on physical receptor association to integrins but, rather, on the activity of the receptor kinase, resulting in transcriptional integrin repression. Interestingly, EGFRvIII intrinsic signals can be propagated by cytokine crosstalk to cells expressing wild-type EGFR, resulting in reduced adhesion and enhanced migration. These data identify potential intrinsic and extrinsic mechanisms that gliomas use to invade surrounding parenchyma.

PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation

The glioblastoma (GB) microenvironment includes cells of the innate immune system identified as glioma-associated microglia/macrophages (GAMs) that are still poorly characterized. A potential role on the mechanisms regulating GAM activity might be played by the endoplasmic reticulum protein ERp57/PDIA3 (protein disulfide-isomerase A3), the modulation of which has been reported in a variety of cancers. Moreover, by using The Cancer Genome Atlas database, we found that overexpression of PDIA3 correlated with about 55% reduction of overall survival of glioma patients. Therefore, we analyzed the expression of ERp57/PDIA3 using specimens obtained after surgery from 18 GB patients. Immunohistochemical analysis of tumor samples revealed ERp57/PDIA3 expression in GB cells as well as in GAMs. The ERp57/PDIA3 levels were higher in GAMs than in the microglia present in the surrounding parenchyma. Therefore, we studied the role of PDIA3 modulation in microglia–glioma interaction, based on the ability of conditioned media collected from human GB cells to induce the activation of microglial cells. The results indicated that reduced PDIA3 expression/activity in GB cells significantly limited the microglia pro-tumor polarization towards the M2 phenotype and the production of pro-inflammatory factors. Our data support a role of PDIA3 expression in GB-mediated protumor activation of microglia.

The diagnostic performance of shear wave velocity ratio for the differential diagnosis of benign and malignant breast lesions: Compared with VTQ, and mammography

PURPOSE: To evaluate the diagnostic value of shear wave velocity (SWV) ratio for the differential diagnosis of benign and malignant breast lesions. MATERIAL AND METHODS: Our retrospective study included 151 breast lesions that were diagnosed by biopsy and surgical pathology. All of the breast lesions were detected by conventional ultrasound and Virtual Touch tissue quantification (VTQ) and mammography. The sonographic characteristics of the breast lesion, such as the internal echo, shape, margin, color flow, and calcification so on, were also observed. The SWV in lesions and surrounding parenchyma were measured and the SWV ratio between the lesion and surrounding parenchyma was calculated. Pathological results were used as a diagnosis standard to compare the value of SWV ratio, VTQ, and mammography in the diagnosis of benign and malignant breast lesions. RESULTS: The 151 breast lesions included 96 benign lesions and 55 malignant lesions. The cutoff value of VTQ in the diagnosis of benign and malignant breast lesions was 5.01 m/s, of SWV ratio was 2.43, and mammography was BI-RADS 4B. The sensitivity, specificity, accuracy and the area under the ROC curve (AUC) of the SWV ratio were 78.2%, 86.5%, 83.4%, and 0.83 respectively. While of SWV ratio with mammography was 86.4%, 89.4%, 88.3% and 0.87, respectively. The sensitivity, specificity, accuracy, and AUC of SWV ratio and SWV ratio with mammography were statistically higher than those of mammography, no statistically higher than VTQ and VTQ with mammography. CONCLUSION: The SWV ratio can improve the sensitivity without sacrificing diagnostic specificity in the process of breast cancer diagnostic, provide a better diagnostic performance, and avoid unnecessary biopsy or surgery.

Studying in vivo dynamics of xylem-transported 11CO2 using positron emission tomography

Respired CO2 in woody tissues can build up in the xylem and dissolve in the sap solution to be transported through the plant. From the sap, a fraction of the CO2 can either be radially diffuse to the atmosphere or be assimilated in chloroplasts present in woody tissues. These processes occur simultaneously in stems and branches, making it difficult to study their specific dynamics. Therefore, an 11C-enriched aqueous solution was administered to young branches of Populus tremula L., which were subsequently imaged by positron emission tomography (PET). This approach allows in vivo visualization of the internal movement of CO2 inside branches at high spatial and temporal resolution, and enables direct measurement of the transport speed of xylem-transported CO2 (vCO2). Through compartmental modeling of the dynamic data obtained from the PET images, we (i) quantified vCO2 and (ii) proposed a new method to assess the fate of xylem-transported 11CO2 within the branches. It was found that a fraction of 0.49 min−1 of CO2 present in the xylem was transported upwards. A fraction of 0.38 min−1 diffused radially from the sap to the surrounding parenchyma and apoplastic spaces (CO2,PA) to be assimilated by woody tissue photosynthesis. Another 0.12 min−1 of the xylem-transported CO2 diffused to the atmosphere via efflux. The remaining CO2 (i.e., 0.01 min−1) was stored as CO2,PA, representing the build-up within parenchyma and apoplastic spaces to be assimilated or directed to the atmosphere. Here, we demonstrate the outstanding potential of 11CO2-based plant-PET in combination with compartmental modeling to advance our understanding of internal CO2 movement and the respiratory physiology within woody tissues.

Unusual histopathologic features in thymic corpuscles associated with porcine periweaning failure-to-thrive syndrome

Six, 5–6-wk-old pigs, from 3 farms of the same company, with significant loss of body condition were submitted for postmortem evaluation. Macroscopically, the main lesion observed in all of the pigs was thymic atrophy. Microscopically, all of the pigs had thymic atrophy, superficial lymphocytic fundic gastritis, atrophic enteritis, superficial colitis, and neutrophilic and lymphocytic rhinitis, leading to a diagnosis of porcine periweaning failure-to-thrive syndrome. In the pigs from 2 of the farms, many of the thymic corpuscles had infiltrates of neutrophils and degenerate cells, in some cases infiltrating the surrounding parenchyma.

Cerebral microbleeds: Beyond the macroscope

While being increasingly recognized in clinical routine, brain microbleeds remain a puzzling finding for physicians. These small dot-like lesions are thought to be old perivascular collections of hemosiderin deposits. They can be found in different neurological settings such as cerebrovascular or neurodegenerative diseases. While their microscopic size would suggest considering these lesions as anecdotal, they are now regarded as biomarkers of severity of an underlying cerebrovascular disease. Their natural history and the interactions with surrounding brain cells remain unknown. However, their presence may impact therapeutic decisions. Deciphering the biological mechanisms leading to, or following microbleeds would enable us to address a key question: do microbleeds arise and impact the surrounding parenchyma like a miniature version of intracerebral hemorrhages or do they represent a different kind of injury? We hereby discuss, based on both clinical and experimental literature, the gap between the definition of microbleeds coming from neuroimaging and the pathophysiological hypotheses raised from histopathological and experimental data. Our analysis supports the need for a convergent effort from clinicians and basic scientists to go beyond the current “macro” view and disclose the cellular and molecular insights of these cerebral hemorrhagic microlesions.