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1

Tabacaru, Gigi, Simona Moldovanu e Marian Barbu. "Algorithm for Analyzing the Microenvironment Surrounding Melanoma". SYSTEM THEORY, CONTROL AND COMPUTING JOURNAL 3, n. 2 (31 dicembre 2023): 15–19. http://dx.doi.org/10.52846/stccj.2023.3.2.52.

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Peritumoral areas or microenvironments surrounding melanoma are unexplored and partially understood, so that, in the following paper, an algorithm that predicts the trend of the melanoma progression is proposed. Additionally, in case of melanoma the peritumoral area is significantly correlated with the texture that belongs inside the skin lesion. The proposed algorithm analyses the region of interest (ROI) with Normalized 2-D cross-correlation (NCC) method and predicts the pattern in the peritumoral area which is most similar with the texture of the melanoma. An important step is the detection of the peritumoral area, in which case, the mathematical morphology techniques were proposed. The verifying of similarity between the samples cropped from inside the melanoma and peritumoral area with Structural Similarity Index (SSIM) was performed. The main advantage of the proposed algorithm is that it can be applied on different medical image types and tumors. The algorithm was tested on two datasets 7-Point and PH2, and two computes.
2

Ly, Ina, Barbara Wichtmann, Susie Yi Huang, Aapo Nummenmaa, Ovidiu Andronesi, Qiuyun Fan, William T. Curry et al. "Characterizing glioma microenvironment with ultra-high gradient diffusion MRI." Journal of Clinical Oncology 35, n. 15_suppl (20 maggio 2017): 2050. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.2050.

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2050 Background: The infiltrating nature of gliomas, particularly into the peritumoral area, is a major barrier to improving clinical outcome as microscopic disease remains even after apparent gross total resection. Conventional T1 post-contrast and T2/FLAIR MRI do not capture full tumor extent. A better imaging biomarker is needed to improve differentiation between tumor, peritumoral area and normal brain. Methods: 4 pre-surgical patients with non-enhancing, FLAIR-hyperintense lesions suspicious for glioma underwent ultra-high gradient diffusion MRI on the Connectome MRI scanner, a unique scanner with maximum gradient strength of 300 mT/m enabling mapping of cellular microstructures on a micron-level scale. The FLAIR area was defined as the tumor region of interest (ROI). Radiographically normal appearing brain up to 1 cm around the FLAIR area was defined as the peritumoral ROI. Using a novel 3 compartment diffusion model (Linear Multiscale Model), the volume fraction of water (VFW) was calculated within restricted (intracellular), hindered (extracellular) and free (CSF) spaces. VFW in the tumor, peritumoral ROI, contralateral normal white matter (WM) and cortex were compared. Results: Within the tumor ROI, the median VFW in the restricted compartment was decreased vs. the peritumoral ROI (↓ 34%), WM (↓ 46%) and cortex (↓ 18%) while median VFW in the hindered compartment was increased vs. the peritumoral ROI (↑ 26%), WM (↑ 54%) and cortex (↑ 25%). Within the peritumoral ROI, median VFW in the hindered compartment was increased compared to WM (↑ 23%). 3 patients had available histopathology revealing isocitrate dehydrogenase-mutant gliomas. Conclusions: Using ultra-high gradient diffusion MRI and a novel diffusion model, we detected distinct diffusion patterns in the tumor and peritumoral area not seen on conventional MRI. Lower VFW in the restricted compartment within the tumor may reflect decreased intracellular water mobility due to enlarged nuclei. Higher VFW in the hindered compartment in the tumor and peritumoral area may reflect higher degree of tissue permeability and edema. MRI-pathology and larger cohort validation studies are underway to elucidate microenvironment changes in response to treatment.
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Kumala Wardani, Bestia, Yuyun Yueniwati e Agus Naba. "The Application of Image Segmentation to Determine the Ratio of Peritumoral Edema Area to Tumor Area on Primary Malignant Brain Tumor and Metastases through Conventional Magnetic Resonance Imaging". Open Access Macedonian Journal of Medical Sciences 10, B (1 gennaio 2022): 26–30. http://dx.doi.org/10.3889/oamjms.2022.7777.

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BACKGROUND: Primary malignant brain tumor and metastases on the brain have a similar pattern in conventional Magnetic Resonance Imaging (MRI), even though both require entirely different treatment and management. The pathophysiological difference of peritumoral edema can help to distinguish the case of primary malignant brain tumor and brain metastases. AIM: This study aimed to analyze the ratio of the area of peritumoral edema to the tumor using Otsu’s method of image segmentation technique with a user-friendly Graphical User Interface (GUI). METODS: Data was prepared by obtaining the examination results of Anatomical Pathology and MRI imaging. The area of peritumoral edema was identified from MRI image segmentation with T2/FLAIR sequence. While the area of tumor was identified using MRI image segmentation with T1 sequence. RESULTS: The Mann-Whitney test was employed to analyze the ratio of the area of peritumoral edema to tumor on both groups. Data testing produced a significance level of 0.013 (p < 0.05) with a median value (Nmax-Nmin) of 1.14 (3.31-0.08) for the primary malignant brain tumor group and a median value (Nmax-Nmin) of 1.17 (10.30-0.90) for the brain metastases group. CONCLUSIONS: There was a significant difference in the ratio of the area of peritumoral edema to the area of tumor from both groups, in which brain metastases have a greater value than the primary malignant brain tumor.
4

Tatagiba, Marcos, Shahram Mirzai e Madjid Samii. "Peritumoral Blood Flow in Intracranial Meningiomas". Neurosurgery 28, n. 3 (1 marzo 1991): 400–404. http://dx.doi.org/10.1227/00006123-199103000-00010.

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Abstract Blood flow was measured in intratumoral tissue, the cerebral hemispheres and particularly in the peritumoral area of 12 patients with intracranial meningiomas using the stable xenon-enhanced computed tomographic scan. Tumor blood flow frequently showed a heterogeneous pattern of enhancement with high flow at the tumor periphery and a central area of hypoperfusion. Blood flow values were on average 28% lower in the peritumoral area than in the ipsilateral cerebral hemisphere. In individual cases, blood flow values in the peritumoral edematous area were very low. These findings suggest that the hypodense area surrounding meningiomas does not solely represent vasogenic edema, but may actually represent tumor pressure ischemia.
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Gao, Xiang, Haiyan Wang, Shanbao Cai, M. Reza Saadatzadeh, Helmut Hanenberg, Karen E. Pollok, Aaron A. Cohen-Gadol e Jinhui Chen. "Phosphorylation of NMDA 2B at S1303 in human glioma peritumoral tissue: implications for glioma epileptogenesis". Neurosurgical Focus 37, n. 6 (dicembre 2014): E17. http://dx.doi.org/10.3171/2014.9.focus14485.

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Object Peritumoral seizures are an early symptom of a glioma. To gain a better understanding of the molecular mechanism underlying tumor-induced epileptogenesis, the authors studied modulation of the N-methyl-d-aspartate (NMDA) receptor in peritumoral tissue. Methods To study the possible etiology of peritumoral seizures, NMDA receptor expression, posttranslational modification, and function were analyzed in an orthotopic mouse model of human gliomas and primary patient glioma tissue in which the peritumoral border (tumor-brain interface) was preserved in a tissue block during surgery. Results The authors found that the NMDA receptor containing the 2B subunit (NR2B), a predominantly extrasynaptic receptor, is highly phosphorylated at S1013 in the neurons located in the periglioma area of the mouse brain. NR2B is also highly phosphorylated at S1013 in the neurons located in the peritumoral area from human brain tissue containing a glioma. The phosphorylation of the extrasynaptic NMDA receptor increases its permeability for Ca2+ influx and subsequently mediates neuronal overexcitation and seizure activity. Conclusions These data suggest that overexcitation of the extrasynaptic NMDA receptors in the peritumoral neurons may contribute to the development of peritumoral seizures and that the phosphorylated NR2B may be a therapeutic target for blocking primary brain tumor–induced peritumoral seizures.
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Zhao, Xinyao, Qingqing Wen, Junying Wang, Weiqiang Dou, Guowei Zhang e Hao Shi. "Is intravoxel incoherent motion magnetic resonance imaging useful for predicting hepatocellular cancer recurrence and invasion of the peritumoral zone after transarterial chemoembolization?" Journal of Cancer Research and Therapeutics 20, n. 2 (aprile 2024): 584–91. http://dx.doi.org/10.4103/jcrt.jcrt_1582_23.

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ABSTRACT Purpose: We evaluated the potential role of intravoxel incoherent motion (IVIM) in predicting the therapeutic response and peritumoral invasion in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Materials and Methods: We enrolled 47 patients previously treated with TACE between January 2018 and December 2021. We evaluated the IVIM-derived metrics [apparent diffusion coefficient (ADC), D, D*, f] in the TACE-treated, peritumoral, and parenchymal areas of the liver. Results: The ADCtace and Dtace values (1.13 ± 0.22 × 10−3 m2/s vs 0.95 ± 0.13 × 10−3 mm2/s, 1.28 ± 0.27 × 10−3 mm2/s vs 1.07 ± 0.3 × 10−3 mm2/s, P < 0.05) were higher in the non-progressing groups than in the progressing groups in the TACE-treated areas. Dpt represented the D values in the peritumoral area, which can distinguish between the progressive and non-progressive groups with an AUC of 0.73. The Dstd values, which represent the D values in the peritumoral area normalized by the D values in the liver parenchyma in the non-progressing groups (1.10 ± 0.14 × 10−3 mm2/s), were higher than those of the progressing groups (0.93 ± 0.17 × 10−3 mm2/s). Conclusion: The ADCtace, Dtace, Dpt, and Dstd values reflect the changes in the microstructure of the progressive and non-progressive groups after TACE treatment, showing robust diagnostic performances in predicting the therapeutic response and peritumoral invasion.
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Danilova, N. V., V. M. Kkomyakov, A. V. Chayka, I. A. Mikhailov, N. A. Oleynikova e P. G. Malkov. "CHARACTERISTICS OF THE IMMUNE MICROENVIRONMENT OF THE NORMAL MUCOUS MEMBRANE OF THE PERITUMORAL AREA IS AN ADDITIONAL INDEPENDENT PROGNOSTIC FACTOR IN GASTRIC CANCER". Siberian journal of oncology 20, n. 1 (6 marzo 2021): 74–86. http://dx.doi.org/10.21294/1814-4861-2021-20-1-74-86.

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The aim of the study was to study and evaluate the predictive value of the immune microenvironment of gastric cancer and morphologically normal mucous membrane of the peritumoral area using an automatic morphometric analysis system on the example of CD 8+ cells.Material and Methods. Surgical samples from 130 patients with a verified diagnosis of gastric cancer were used. After immunohistochemical staining with antibodies to CD 8, a morphological assessment was performed according to the original method. We assessed the average area of CD 8+ cells in three fields of view (lens magn. ×20) using the automatic system of morphometric analysis LAS X (Leica) in the central part of the tumor and areas of morphologically normal mucous membrane of the peritumoral region directly adjacent to the tumor tissue. The results were compared with the main clinical and morphological characteristics of the tumor as well as with the overall five-year survival of patients.Results and Discussion. A high density of CD 8+ infiltration of normal mucous membrane of the peritumoral area was observed in groups T4a and T4b by the depth of invasion (n=96, p=0.0089) and was associated with the presence of emboli in the lymphatic vessels (n=96, p=0.0102) and with the more advanced stage of gastric cancer (n=96, p=0.0107). The studied cases were divided into two groups: less than 3300 square micrometers (better patient survival; n=79, p=0.01) and more than 3300 square micrometers according to the average area of CD 8+ cells in normal mucous membrane of the peritumoral area. According to multivariate survival analysis using the Cox regression model, it was found that the average area of CD 8+ cells in normal mucous membrane of the peritumoral area was a significant negative prognostic factor (RR=1.537; CI : 0.761–3.105; p<0.01) comparable in degree covariance with the stage of the tumor A similar indicator assessed in central part of the tumor was not significantly associated with patient survival (RR=0.803; CI : 0.574–1.122; p>0.05).Conclusion. The possibility of using an automatic analysis system to evaluate the immune microenvironment in gastric cancer was demonstrated for the first time. It was found that a high level of CD 8+ lymphocyte infiltration of morphologically normal mucous membrane of the peritumoral area was an independent negative prognostic factor. Therefore, we recommend the mandatory preoperative biopsy sampling from the mucous membrane of the peritumoral region for morphometric assessment of CD 8+ lymphocyte infiltration.
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Boia, Eugen Radu, Simina Boia, Raluca Amalia Ceausu, Pusa Nela Gaje, Sarrah Mariam Maaroufi, Florica Sandru e Marius Raica. "The Follicular Dendritic Cells and HPV 18 Interrelation in Head and Neck Squamous Cell Carcinomas of the Larynx". Medicina 59, n. 6 (2 giugno 2023): 1072. http://dx.doi.org/10.3390/medicina59061072.

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Background and Objectives: Even if they are cells of controversial origin (mesenchymal, perivascular, or fibroblastic), follicular dendritic cells (FDC) are present in all organs. The aim of this study was to establish the FDC expression pattern and its interrelation with HPV 18 expression in laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Fifty-six cases of LSCC were evaluated by simple and double immunostaining. The following score was used: 0 (negative or few positive cells), 1 (10–30% of positive cells), 2 (30–50% of cells), and 3 (over 50% of cells). Results: The expression of CD 21-positive cells with dendritic morphology (CDM) was noticed in the intratumoral area of conventional (well and poorly differentiated types and HPV 18 positive cases with a value of 2 for the score) and papillary types (HPV-18 negative cases with a score of 1). The highest value of 2 for the score of CDM in HPV-18 positive cases was found in the peritumoral area of well- and poorly-differentiated conventional LSCCs. A significant correlation was found between scores of CDM from the intratumoral area and those of the peritumoral area (p = 0.001), between CDM and non-dendritic morphology cells (NDM) of the intratumoral area (p = 0.001), and between HPV-18 status and peritumoral NDM cells (p = 0.044). Conclusions: The FDC and NDM cell score values of intratumoral and peritumoral areas may represent important parameters of LSCCs. This may contribute to a better stratification of laryngeal carcinoma cases and the individualized selection of clinical treatment protocols.
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Lee, Hongseok, Kyungdoc Kim, Guhyun Kang, Kyu-Hwan Jung e Sunyoung S. Lee. "Abstract 1721: Spatial distribution of immune cells as quantitative prognosis indicator in hepatocellular carcinoma". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 1721. http://dx.doi.org/10.1158/1538-7445.am2022-1721.

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Abstract Background: We previously demonstrated that the analysis of the tumor microenvironment (TME) in histopathology images via tissue segmentation [1] and cell density in lymphocyte-rich area [2] impacts prognosis and treatment in hepatocellular carcinoma (HCC). Few biomarker models exist to prognosticate patients with HCC via the automated analysis of TME at the cellular level. Methods: Clinical outcomes data and histopathology images of 351 patients with HCC were obtained from TCGA. We advanced a deep learning-based algorithm to analyze the tumor volume and spatial distribution of nuclei in TME. This was based on combination of two models: the PAIP2019 dataset was used for DenseNet-based HCC segmentation, which showed the performance of 0.8582 on the F1-score metric [3]; HoverNet-based cell detection model, which showed the performance of 0.654 on the binary PQ metric, annotated lymphocytes, macrophages, and neutrophils on the MonuSac dataset [4]. Results: The HCC segmentation model divided the TME into tumoral, marginal, and peritumoral areas by image processing. The marginal and peritumoral areas were defined as inner 50 um area and outer 100 um area from the estimated tumoral boundary, respectively. The ratios of neutrophils, lymphocytes, macrophages to the total cell count on marginal and peritumoral areas were calculated through integration of HCC segmentation and cell detection models. The proportions of leukocytes were subjected into Cox proportional hazard analysis. The results of Cox proportional hazard analysis calculated the proportions of macrophages and lymphocytes to other cells in the TME. The macrophage proportion on the peritumoral area was a significant prognostic indicator showing Log(hazard ratio) (-2.42 ± 2.14, p=0.026). The lymphocyte proportion on both areas of the peritumor and margins showed significant Log(hazard ratio) (-1.70 ± 1.61, p=0.042). Conclusions: The retrospective analysis of the TME using deep learning-assisted algorithm combining tissue segmentation and cell detection models reveals that the ratio of lymphocytes and macrophages in the peri-tumoral areas of HCC TME significantly impact prognosis. Further analyses in the prospective studies may provide more information about cellular biomarkers. [1] Kim et al. Cancer Res 2020 (80) (16 Supp) 2631 [2] Park et al. Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 4107-4107 [3] Kim, Yoo Jung, Jang, Hyungjoon, Lee, Kyoungbun et al. Medical Image Analysis 67 (2021): 101854. [4] Verma, Ruchika. IEEE Transactions on Medical Imaging 39 (2020): 1380-1391. [5] Graham, Simon. Medical Image Analysis 58 (2019): 101563. Citation Format: Hongseok Lee, Kyungdoc Kim, Guhyun Kang, Kyu-Hwan Jung, Sunyoung S. Lee. Spatial distribution of immune cells as quantitative prognosis indicator in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1721.
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Samani, Zahra Riahi, Drew Parker, Jacob Antony Alappatt, Steven Brem e Ragini Verma. "NIMG-21. DIFFERENTIATING TUMOR TYPES BASED ON THE PERITUMORAL MICROENVIRONMENT USING CONVOLUTIONAL NEURAL NETWORKS". Neuro-Oncology 22, Supplement_2 (novembre 2020): ii151. http://dx.doi.org/10.1093/neuonc/noaa215.634.

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Abstract PURPOSE The differential diagnosis of glioblastoma (GBM) versus single brain metastasis (Met) is clinically important, and is undertaken with a clinical reading of MR images and/or tumor biopsy. We investigate whether Mets and GBMs can be differentiated based on the microstructure of the FLAIR-hyperintense peritumoral region measured by diffusion tensor imaging (DTI). We hypothesize that the peritumoral microstructure differs in extracellular water content, based on whether it is vasogenic edema or infiltrative. We use deep learning trained on DTI-based free-water volume fraction maps to discriminate between the peritumoral regions of Met and GBM neoplasms. Our results are also compared with mean diffusivity (MD), the most commonly used DTI metric. METHOD dMRI data of 143 patients with brain tumors (89 glioblastomas and 54 metastases, ages 19-87 years, 77 females and 66 males) were included. Free-water volume fraction maps were computed for the peritumoral regions (demarcated automatically). We developed a 7-layer convolutional neural network (CNN) architecture to distinguish microstructural patterns of Met and GBM tumors using 32 x 32 mm patches placed at random in the peritumoral area. The CNN was trained on patches from a training set of 113 patients and tested on the remaining 30 patients, where majority voting was applied to predict the tumor type for each patient. Although MD has been previously used in both tumor and peritumoral area for discriminating tumor type, we replicated the same process with MD only in the peritumoral area to provide a stronger comparison. RESULT We predicted tumor type with 93% accuracy, outperforming MD with 84% accuracy. CONCLUSION Our results demonstrate that deep learning with CNN on DTI-based free-water volume fraction map can be a promising tool for automatic distinction of tumor types, and has potential as a tumor biomarker.
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López, Carlos, Ramón Bosch-Príncep, Guifré Orero, Laia Fontoura Balagueró, Anna Korzynska, Marcial García-Rojo, Gloria Bueno et al. "Peritumoral immune infiltrates in primary tumours are not associated with the presence of axillary lymph node metastasis in breast cancer: a retrospective cohort study". PeerJ 8 (2 settembre 2020): e9779. http://dx.doi.org/10.7717/peerj.9779.

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Background The axillary lymph nodes (ALNs) in breast cancer patients are the body regions to where tumoral cells most often first disseminate. The tumour immune response is important for breast cancer patient outcome, and some studies have evaluated its involvement in ALN metastasis development. Most studies have focused on the intratumoral immune response, but very few have evaluated the peritumoral immune response. The aim of the present article is to evaluate the immune infiltrates of the peritumoral area and their association with the presence of ALN metastases. Methods The concentration of 11 immune markers in the peritumoral areas was studied in 149 patients diagnosed with invasive breast carcinoma of no special type (half of whom had ALN metastasis at diagnosis) using tissue microarrays, immunohistochemistry and digital image analysis procedures. The differences in the concentration of the immune response of peritumoral areas between patients diagnosed with and without metastasis in their ALNs were evaluated. A multivariate logistic regression model was developed to identify the clinical-pathological variables and the peritumoral immune markers independently associated with having or not having ALN metastases at diagnosis. Results No statistically significant differences were found in the concentrations of the 11 immune markers between patients diagnosed with or without ALN metastases. Patients with metastases in their ALNs had a higher histological grade, more lymphovascular and perineural invasion and larger-diameter tumours. The multivariate analysis, after validation by bootstrap simulation, revealed that only tumour diameter (OR = 1.04; 95% CI [1.00–1.07]; p = 0.026), lymphovascular invasion (OR = 25.42; 95% CI [9.57–67.55]; p < 0.001) and histological grades 2 (OR = 3.84; 95% CI [1.11–13.28]; p = 0.033) and 3 (OR = 5.18; 95% CI [1.40–19.17]; p = 0.014) were associated with the presence of ALN metastases at diagnosis. This study is one of the first to study the association of the peritumoral immune response with ALN metastasis. We did not find any association of peritumoral immune infiltrates with the presence of ALN metastasis. Nevertheless, this does not rule out the possibility that other peritumoral immune populations are associated with ALN metastasis. This matter needs to be examined in greater depth, broadening the types of peritumoral immune cells studied, and including new peritumoral areas, such as the germinal centres of the peritumoral tertiary lymphoid structures found in extensively infiltrated neoplastic lesions.
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Simińska, Donata, Klaudyna Kojder, Dariusz Jeżewski, Maciej Tarnowski, Patrycja Tomasiak, Katarzyna Piotrowska, Agnieszka Kolasa, Kapczuk Patrycja, Dariusz Chlubek e Irena Baranowska-Bosiacka. "Estrogen α and β Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model". International Journal of Molecular Sciences 25, n. 7 (8 aprile 2024): 4130. http://dx.doi.org/10.3390/ijms25074130.

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Glioblastoma multiforme (GBM) is a malignant tumor with a higher prevalence in men and a higher survival rate in transmenopausal women. It exhibits distinct areas influenced by changing environmental conditions. This study examines how these areas differ in the levels of estrogen receptors (ERs) which play an important role in the development and progression of many cancers, and whose expression levels are often correlated with patient survival. This study utilized two research models: an in vitro model employing the U87 cell line and a second model involving tumors resected from patients (including tumor core, enhancing tumor region, and peritumoral area). ER expression was assessed at both gene and protein levels, with the results validated using confocal microscopy and immunohistochemistry. Under hypoxic conditions, the U87 line displayed a decrease in ERβ mRNA expression and an increase in ERα mRNA expression. In patient samples, ERβ mRNA expression was lower in the tumor core compared to the enhancing tumor region (only in males when the study group was divided by sex). In addition, ERβ protein expression was lower in the tumor core than in the peritumoral area (only in women when the study group was divided by sex). Immunohistochemical analysis indicated the highest ERβ protein expression in the enhancing tumor area, followed by the peritumoral area, and the lowest in the tumor core. The findings suggest that ER expression may significantly influence the development of GBM, exhibiting variability under the influence of conditions present in different tumor areas.
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Samani, Zahra Riahi, Drew Parker, Jacob Antony Alappatt, Steven Brem e Ragini Verma. "NIMG-45. DEEP LEARNING-BASED PERITUMORAL MICROSTRUCTURE MAPPING IN GLIOBLASTOMAS USING FREE WATER VOLUME FRACTION". Neuro-Oncology 22, Supplement_2 (novembre 2020): ii157—ii158. http://dx.doi.org/10.1093/neuonc/noaa215.658.

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Abstract PURPOSE Characterization of the peritumoral microenvironment is a widely researched, but as yet unsolved problem. Determining the tissue microstructure differences between tumor types, arising from differences in infiltration, edema, and disease driven changes in cellularity is important to be able to guide treatment options. Diffusion tensor imaging with characterization of extracellular free water provides unique information of the tissue microstructure. The goal of this work is to leverage this information by applying deep learning on free water maps and create a microstructure map of the peritumoral area, to aid in targeted resection, radiotherapy and treatment management in the form of a crucial supplemental radiomic feature, replacing all other diffusion derived measures. METHOD We leveraged the widely different peritumoral microenvironments of GBMs and Metastatic tumors to create the microstructure maps. Tumor and peritumoral regions were automatically delineated in 143 patients with brain tumors (89 glioblastomas and 54 metastasis, ages 19-87 years, 77 females), and free water maps were computed in the peritumoral regions using their DTI data. We trained a Convolutional Neural Network (CNN) on 32x32 mm patches in the peritumoral area from GBMs and Mets, labeled as non-enhancing tumor (low free-water) and edema (high free-water), respectively. An independent test set was used and the CNN associated a voxel-wise probability to their peritumoral region to produce microstructure maps of GBMs and Mets which were then statistically compared. RESULT For comparison, a t-test was used showing significant group difference in the microstructure map between Mets and GBMs (p&lt; 0.05). CONCLUSION The voxel-wise microstructure map is able to capture the cellularity differences in the peritumoral region, based on DTI-based characterization of the tissue microstructure. CLINICAL IMPORTANCE The microstructure map provides a novel insight into the peritumoral microenvironment using a measure that can be derived from clinically feasible DTI data, replacing pre-existing DTI measures.
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Yan, Jiun-Lin, Chao Li, Natalie R. Boonzaier, Daniel M. Fountain, Timothy J. Larkin, Tomasz Matys, Anouk van der Hoorn e Stephen J. Price. "Multimodal MRI characteristics of the glioblastoma infiltration beyond contrast enhancement". Therapeutic Advances in Neurological Disorders 12 (gennaio 2019): 175628641984466. http://dx.doi.org/10.1177/1756286419844664.

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Our inability to identify the invasive margin of glioblastomas hampers attempts to achieve local control. Diffusion tensor imaging (DTI) has been implemented clinically to delineate the margin of the tumor infiltration, its derived anisotropic (q) values can extend beyond the contrast-enhanced area and correlates closely with the tumor. However, its correlation with tumor infiltration shown on multivoxel proton magnetic resonance spectroscopy1 (MRS) and perfusion magnetic resonance imaging (MRI) should be investigated. In this study, we aimed to show tissue characteristics of the q-defined peritumoral invasion on MRS and perfusion MRI. Patients with a primary glioblastoma were included ( n = 51). Four regions of interest were analyzed; the contrast-enhanced lesion, peritumoral abnormal q region, peritumoral normal q region, and contralateral normal-appearing white matter. MRS, including choline (Cho)/creatinine (Cr), Cho/N-acetyl-aspartate (NAA) and NAA/Cr ratios, and the relative cerebral blood volume (rCBV) were analyzed. Our results showed an increase in the Cho/NAA ( p = 0.0346) and Cho/Cr ( p = 0.0219) ratios in the peritumoral abnormal q region, suggestive of tumor invasion. The rCBV was marginally elevated ( p = 0.0798). Furthermore, the size of the abnormal q regions was correlated with survival; patients with larger abnormal q regions showed better progression-free survival (median 287 versus 53 days, p = 0.001) and overall survival (median 464 versus 274 days, p = 0.006) than those with smaller peritumoral abnormal q regions of interest. These results support how the DTI q abnormal area identifies tumor activity beyond the contrast-enhanced area, especially correlating with MRS.
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Korbecki, Jan, Klaudyna Kojder, Dariusz Jeżewski, Donata Simińska, Maciej Tarnowski, Patrycja Kopytko, Krzysztof Safranow et al. "Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme". Biomolecules 10, n. 5 (7 maggio 2020): 727. http://dx.doi.org/10.3390/biom10050727.

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The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl–coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells.
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Sun, Xiaojun, Peipei Pang, Lin Lou, Qi Feng, Zhongxiang Ding e Jian Zhou. "Radiomic prediction models for the level of Ki-67 and p53 in glioma". Journal of International Medical Research 48, n. 5 (maggio 2020): 030006052091446. http://dx.doi.org/10.1177/0300060520914466.

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Objective To identify glioma radiomic features associated with proliferation-related Ki-67 antigen and cellular tumour antigen p53 levels, common immunohistochemical markers for differentiating benign from malignant tumours, and to generate radiomic prediction models. Methods Patients with glioma, who were scanned before therapy using standard brain magnetic resonance imaging (MRI) protocols on T1 and T2 weighted imaging, were included. For each patient, regions-of-interest (ROI) were drawn based on tumour and peritumoral areas (5/10/15/20 mm), and features were identified using feature calculations, and used to create and assess logistic regression models for Ki-67 and p53 levels. Results A total of 92 patients were included. The best area under the curve (AUC) for the Ki-67 model was 0.773 for T2 weighted imaging in solid glioma (sensitivity, 0.818; specificity, 0.833), followed by a less reliable AUC of 0.773 (sensitivity, 0.727; specificity 0.667) in 20-mm peritumoral areas. The highest AUC for the p53 model was 0.709 (sensitivity, 1; specificity, 0.4) for T2 weighted imaging in 10-mm peritumoral areas. Conclusion Using T2-weighted imaging, the prediction model for Ki-67 level in solid glioma tissue was better than the p53 model. The 20-mm and 10-mm peritumoral areas in the Ki-67 and p53 model, respectively, showed predictive effects, suggesting value in further research into areas without conventional MRI features.
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Cepeda, Santiago, Luigi Luppino, Marek Wodsinski, Ole Solheim, Angel Perez-Nuñez, Sergio Garcia-Garcia, Anna Karlberg et al. "NIMG-45. EXTERNAL EVALUATION OF A MACHINE LEARNING MODEL EMPLOYING RADIOMICS TO IDENTIFY REGIONS OF LOCAL RECURRENCE IN GLIOBLASTOMA FROM POSTOPERATIVE MRI". Neuro-Oncology 25, Supplement_5 (1 novembre 2023): v195—v196. http://dx.doi.org/10.1093/neuonc/noad179.0741.

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Abstract The standard surgical goal for operable glioblastomas worldwide is the complete excision of the enhancing tumor. Nevertheless, the peritumoral region harbors infiltrating cells leading to recurrence. Our study aims to evaluate a predictive model designed to predict potential regions of recurrence using voxel-based radiomics analysis on postoperative magnetic resonance imaging (MRI). This retrospective, multi-institutional study involved glioblastoma patients who had undergone complete resection. The training cohort comprised 49 patients from two Spanish institutions, with model evaluation using an external dataset of 27 patients from a Norwegian institution and the public Ivy-Gap dataset. We used follow-up MRI scans for ground truth definition of recurrence, while postoperative multiparametric MRI scans provided the data for extracting voxel-based radiomic features. Our method employed an unsupervised, hybrid approach, which combined a deep neural network and instance optimization, to align the MRI sequences for each patient, registering the follow-up with the postoperative scans. To generate ground truth labels, we segmented the peritumoral region in the postoperative scans, identified as the area showing T2/FLAIR signal alterations, in addition to the enhancing tumor visible in the registered follow-up scan. Overlapping voxels between the peritumoral and enhancing tumor regions were classified as recurrence, while non-overlapping voxels were labeled as nonrecurrence. Radiomic features were subsequently extracted from the postoperative peritumoral region. We trained four machine learning classifiers to predict recurrence. Among these, the Categorical Boosting (CatBoost) classifier demonstrated excellent performance on the test dataset, achieving an average area under the curve (AUC) of 0.83 ± 0.07, and an accuracy of 0.80 ± 0.12, based on voxel-wise comparison with the ground truth. Our study resulted in a method that accurately predicts the area of future tumor recurrence in glioblastoma patients' MRI scans. This innovation could potentially tailor surgical and radiotherapy treatment strategies to these specific areas, possibly extending patient survival.
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Zimmermann, Mona, Lucas Breedt, Eduarda Centeno, Shanna Kulik, Fernando Santos, Cornelis Stam, Marike van Lingen, Arjan Hillebrand e Linda Douw. "CNSC-10. THE COMPLEX RELATIONSHIP BETWEEN NEURONAL ACTIVITY AND FUNCTIONAL NETWORK PROPERTIES IN GLIOMA PATIENTS". Neuro-Oncology 24, Supplement_7 (1 novembre 2022): vii23—vii24. http://dx.doi.org/10.1093/neuonc/noac209.091.

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Abstract BACKGROUND Glioma is associated with pathologically high peritumoral neuronal activity, which associates with faster tumor progression. Concurrently, glioma patients have local and widespread disturbances of the functional brain network as measured with magnetoencephalography (MEG), such as higher network clustering (the extent to which regions connected to a particular area are also connected to each other) and locally altered integrative connectivity (for instance assessed with a centrality measure). How local neuronal activity and nodal network properties relate to each other has yet to be investigated. METHODS We obtained eyes-closed resting-state MEG in 95 de novo glioma patients and 57 matched healthy controls (HCs). The offset of the power spectrum was calculated for 210 cortical atlas regions as a proxy for neuronal activity. Regional clustering coefficient (CC) and eigenvector centrality (EC) were calculated in the delta, theta and alpha bands. Offset and network values were then averaged across peritumoral regions, contralateral homologue regions and all non-peritumoral regions. Linear mixed models were used to relate nodal CC and EC to local offset in patients and HCs. RESULTS The peritumoral area was significantly more active than the non-peritumoral homologue in patients, and showed pathologically high activity in comparison to HCs. However, patients’ functional network was disturbed globally, showing higher clustering and lower centrality than HCs. Whereas high activity related to high centrality in HCs and patients alike, high activity seemed to relate to low clustering in non-peritumoral regions in patients, but not HCs. CONCLUSION We find that the relationship between neuronal activity and functional network properties is disturbed in a complex manner in glioma patients. Our results further underline the importance of investigating how local activity may impact global network topology in order to understand how neuron-glioma interactions shape brain functioning.
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Cherdantseva, T. M., I. P. Bobrov, I. V. Klimachev e V. N. Baranov. "Proliferative and apoptotic processes in peritumoral area of kidney cancer". Russian Journal of Oncology 20, n. 4 (15 agosto 2015): 50–51. http://dx.doi.org/10.17816/onco40270.

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Zhang, L., T. Yoshimura e D. T. Graves. "Antibody to Mac-1 or monocyte chemoattractant protein-1 inhibits monocyte recruitment and promotes tumor growth." Journal of Immunology 158, n. 10 (15 maggio 1997): 4855–61. http://dx.doi.org/10.4049/jimmunol.158.10.4855.

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Abstract Human tumors are frequently infiltrated by numerous monocytes/macrophages, which can be found within the tumor mass (intratumoral) or surrounding the tumor (peritumoral). The functional role that these monocytes/macrophages play in tumor growth is controversial. To address this issue we inhibited intratumoral monocyte/macrophage recruitment with mAbs that either blocked integrin function or neutralized a tumor-produced chemotactic protein. Both treatments significantly increased tumor formation and accelerated tumor growth. Surprisingly, the same results were obtained when recruitment of peritumoral or intratumoral monocytes/macrophages was blocked. Our findings are contrary to one of the purported roles of monocytes/macrophages, particularly in the peritumoral area, since we found no evidence for monocyte/macrophage-supported tumor growth. These results provide direct evidence that intratumoral as well as peritumoral monocytes/macrophages act to limit tumor size in the early stages following tumor inoculation and provide a mechanism that accounts for monocyte/macrophage recruitment to human tumors.
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Angelucci, Cristiana, Alessio D’Alessio, Silvia Sorrentino, Filippo Biamonte, Umberto Moscato, Annunziato Mangiola, Gigliola Sica e Fortunata Iacopino. "Immunohistochemical Analysis of DNA Repair- and Drug-Efflux-Associated Molecules in Tumor and Peritumor Areas of Glioblastoma". International Journal of Molecular Sciences 22, n. 4 (5 febbraio 2021): 1620. http://dx.doi.org/10.3390/ijms22041620.

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Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients’ survival suggests a prognostic role for this protein.
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Fuster-Garcia, Elies, Ivar Thokle Hovden, Siri Fløgstad Svensson, Christopher Larsson, Jonas Vardal, Atle Bjørnerud e Kyrre E. Emblem. "Quantification of Tissue Compression Identifies High-Grade Glioma Patients with Reduced Survival". Cancers 14, n. 7 (28 marzo 2022): 1725. http://dx.doi.org/10.3390/cancers14071725.

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The compression of peritumoral healthy tissue in brain tumor patients is considered a major cause of the life-threatening neurologic symptoms. Although significant deformations caused by the tumor growth can be observed radiologically, the quantification of minor tissue deformations have not been widely investigated. In this study, we propose a method to quantify subtle peritumoral deformations. A total of 127 MRI longitudinal studies from 23 patients with high-grade glioma were included. We estimate longitudinal displacement fields based on a symmetric normalization algorithm and we propose four biomarkers. We assess the interpatient and intrapatient association between proposed biomarkers and the survival based on Cox analyses, and the potential of the biomarkers to stratify patients according to their survival based on Kaplan–Meier analysis. Biomarkers show a significant intrapatient association with survival (p < 0.05); however, only compression biomarkers show the ability to stratify patients between those with higher and lower overall survival (AUC = 0.83, HR = 6.30, p < 0.05 for CompCH). The compression biomarkers present three times higher Hazard Ratios than those representing only displacement. Our study provides a robust and automated method for quantifying and delineating compression in the peritumoral area. Based on the proposed methodology, we found an association between lower compression in the peritumoral area and good prognosis in high-grade glial tumors.
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Greco, Federico, Luigi Giuseppe Quarta, Rosario Francesco Grasso, Bruno Beomonte Zobel e Carlo Augusto Mallio. "Increased visceral adipose tissue in clear cell renal cell carcinoma with and without peritumoral collateral vessels". British Journal of Radiology 93, n. 1112 (agosto 2020): 20200334. http://dx.doi.org/10.1259/bjr.20200334.

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Objective: The excessive amount of adipose tissue, mainly visceral, determines adiposopathy. With respect to oncogenesis, visceral adipose tissue (VAT) releases secretes adipokines, proinflammatory citokines and growth factors, considered mediating molecules in the development of obesity-related tumors. In this study, we quantify VAT in male patients with clear cell renal cell carcinoma (ccRCC) subgrouped according to the presence or absence of peritumoral collateral vessels. Methods: in this retrospective study, we enrolled 141 male caucasian patients divided into 2 groups: the ccRCC group (n = 106) composed of patients with ccRCC and control group (n = 35). The ccRCC group was further divided into two subgroups: the ccRCCa subgroup which showed absence of collateral vessels (n = 48) and ccRCCp subgroup with collateral vessels (n = 58). Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in the groups and subgroups. VAT/SAT ratio was calculated for each subject. Results: Statistically significant differences were obtained between ccRCC group and control group for TAT area (p < 0.005), VAT area (p < 0.005) and SAT area (p = 0.01). Between ccRCCa subgroup and control group for TAT area (p < 0.001), VAT area (p = 0.005) and SAT area (p = 0.001). Between ccRCCp subgroup and control group for TAT area (p = 0.01) and VAT area (p = 0.01). Conclusion: This study confirms the increase of abdominal, especially visceral, adipose tissue in ccRCC patients and demonstrates a significant VAT accumulation in both categories of patients with and without peritumoral collateral vessels. Advances in knowledge: Visceral adiposity is present in patients with ccRCC regardless the presence of peritumoral collateral vessels, with surprisingly stronger results in the ccRCCa subgroup.
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Chiu, Fang-Ying, Nguyen Quoc Khanh Le e Cheng-Yu Chen. "A Multiparametric MRI-Based Radiomics Analysis to Efficiently Classify Tumor Subregions of Glioblastoma: A Pilot Study in Machine Learning". Journal of Clinical Medicine 10, n. 9 (10 maggio 2021): 2030. http://dx.doi.org/10.3390/jcm10092030.

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Glioblastoma multiforme (GBM) carries a poor prognosis and usually presents with heterogenous regions of a necrotic core, solid part, peritumoral tissue, and peritumoral edema. Accurate demarcation on magnetic resonance imaging (MRI) between the active tumor region and perifocal edematous extension is essential for planning stereotactic biopsy, GBM resection, and radiotherapy. We established a set of radiomics features to efficiently classify patients with GBM and retrieved cerebral multiparametric MRI, including contrast-enhanced T1-weighted (T1-CE), T2-weighted, T2-weighted fluid-attenuated inversion recovery, and apparent diffusion coefficient images from local patients with GBM. A total of 1316 features on the raw MR images were selected for each annotated area. A leave-one-out cross-validation was performed on the whole dataset, the different machine learning and deep learning techniques tested; random forest achieved the best performance (average accuracy: 93.6% necrosis, 90.4% solid part, 95.8% peritumoral tissue, and 90.4% peritumoral edema). The features from the enhancing tumor and the tumor shape elongation of peritumoral edema region for high-risk groups from T1-CE. The multiparametric MRI-based radiomics model showed the efficient classification of tumor subregions of GBM and suggests that prognostic radiomic features from a routine MRI exam may also be significantly associated with key biological processes that affect the response to chemotherapy in GBM.
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Greco, Federico, Luigi Giuseppe Quarta, Aldo Carnevale, Melchiore Giganti, Rosario Francesco Grasso, Bruno Beomonte Zobel e Carlo Augusto Mallio. "Subcutaneous Adipose Tissue Reduction in Patients with Clear Cell Renal Cell Carcinoma and Peritumoral Collateral Vessels: A Retrospective Observational Study". Applied Sciences 11, n. 13 (30 giugno 2021): 6076. http://dx.doi.org/10.3390/app11136076.

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Background: peritumoral collateral vessels adjacent to renal cell carcinoma (RCC) can be encountered in clinical practice. Cancer cachexia is defined as a decrease of adipose and skeletal muscle tissues. In this study we evaluated, using a quantitative CT imaging-based approach, the distribution of abdominal adipose tissue in clear cell RCC (ccRCC) male patients with and without collateral vessels. Methods: between November 2019 and February 2020, in this retrospective study we enrolled 106 ccRCC male Caucasian patients divided into two groups: a ccRCCa group without collateral vessels (n = 48) and a ccRCCp group with collateral vessels (n = 58). The total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured in both groups. Moreover, the VAT/SAT ratio was calculated for each subject. Results: a statistically significant difference between the two groups was found in the SAT area (p < 0.05), while no significant differences were found in the TAT area, VAT area and VAT/SAT ratio. Conclusion: this study demonstrates a reduction of SAT in ccRCC patients with peritumoral collateral vessels.
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Samani, Zahra Riahi, Drew Parker, Ronald Wolf, Steven Brem e Ragini Verma. "BRMP-04. AI-based biomarker of the peritumoral region using tissue microstructure". Neuro-Oncology 23, Supplement_6 (2 novembre 2021): vi223—vi224. http://dx.doi.org/10.1093/neuonc/noab196.897.

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Abstract PURPOSE Glioblastomas, the most common malignant brain tumor [BS1], infiltrate into peritumoral brain structures, making clinical management challenging. An unmet need is to develop a biomarker that reliably characterize infiltration in the peritumoral region, where surgical biopsy or resection may be hazardous. Diffusion tensor imaging (DTI) with multicompartment modeling can characterize extracellular free water, providing unique information of the tissue microstructure that is able to capture this heterogeneity. We propose a novel biomarker based on peritumoral tissue microstructure, using deep-learning on DTI-based free water map. METHOD Peritumoral regions were automatically segmented for 136 patients with brain tumors (86 glioblastomas and 50 metastases, ages 23–87 years, 65 females). We trained a Convolutional Neural Network (CNN) on free-water maps using automatically defined patches in the peritumoral area from glioblastomas and metastases, labeled as low free-water and high free-water to extract a microstructural index for each voxel. To extract the biomarker, we grouped peritumoral voxels into connected components (CCs) where adjacent voxels have high (&gt;0.9) microstructural index values. Two independent test sets related to two clinically significant problems were evaluated: i) metastases vs. glioblastomas; ii) glioma patients categorized into short and long survival groups and the number of CCs were statistically compared. RESULT Two-sample t-tests showed significant group difference in the number of CCs between metastases and glioblastomas (p&lt; 0.05), and short and long-survivals (p&lt;0.05) with higher number of CCs in metastases and long-survivals, which suggests smaller number of voxels in CCs. CONCLUSION The proposed biomarker based on CCs of microstructural index captures the differences in infiltration of the peritumoral region, showing larger CCs in glioblastomas and short-survivals corresponding to higher infiltration. CLINICAL IMPORTANCE The proposed biomarker provides a novel insight into the peritumoral microenvironment and can be derived from clinically feasible DTI data, providing new possibilities for the diagnosis and treatment of glioblastoma.
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Chen, Ran-Chou, Chao-Shiang Li, Jiunn-Ming Lii, Wei-Tsung Chen e Hsing-Yang Tu. "Peritumoral fat-spared area is well correlated with the presence of temporal peritumoral enhancement in hepatic hemangioma in fatty liver". Journal of Magnetic Resonance Imaging 22, n. 1 (2005): 86–91. http://dx.doi.org/10.1002/jmri.20343.

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Lee, Jeong Won, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Sung Hoon Hong, Sang Mi Lee e In Young Jo. "Clinical Significance of Peritumoral Adipose Tissue PET/CT Imaging Features for Predicting Axillary Lymph Node Metastasis in Patients with Breast Cancer". Journal of Personalized Medicine 11, n. 10 (15 ottobre 2021): 1029. http://dx.doi.org/10.3390/jpm11101029.

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We investigated whether textural parameters of peritumoral breast adipose tissue (AT) based on F-18 fluorodeoxyglucose (FDG) PET/CT could predict axillary lymph node metastasis in patients with breast cancer. A total of 326 breast cancer patients with preoperative FDG PET/CT were retrospectively enrolled. PET/CT images were visually assessed and the maximum FDG uptake of axillary lymph nodes (LN SUVmax) was measured. From peritumoral breast AT, 38 textural features of PET imaging were extracted. The diagnostic ability of PET based on visual analysis, LN SUVmax, and textural features of peritumoral breast AT for predicting axillary lymph node metastasis were assessed using the area under the receiver operating characteristic curve (AUC) values. Among the 38 peritumoral breast AT textural features, grey-level co-occurrence matrix (GLCM) entropy showed the highest AUC value (0.830) for predicting axillary lymph node metastasis. The value of GLCM entropy was higher than that of visual analysis (0.739; p < 0.05) and the AUC value was comparable to that of LN SUVmax (0.793; p > 0.05). In the subgroup analysis of patients with negative findings on visual analysis, GLCM entropy still showed a high diagnostic ability (AUC: 0.759) in predicting lymph node metastasis. The findings suggest a potential diagnostic role of PET/CT imaging features of peritumoral breast AT in predicting axillary lymph node metastasis in patients with breast cancer.
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Dzhenkova, E. A., E. A. Mirzoyan, A. B. Sagakyants, E. S. Bondarenko, E. Yu Zlatnik, A. V. Shaposhnikov, E. N. Kolesnikov et al. "Evaluation of Toll-like receptors expression in terms of colon cancer". Research and Practical Medicine Journal 9, n. 4 (1 dicembre 2022): 63–71. http://dx.doi.org/10.17709/2410-1893-2022-9-4-6.

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Purpose of the study. To evaluate the number of cells with the CD45+/- phenotype expressing Toll-like receptors (TLRs) in tissues of the tumor, peritumoral area and resection line tissues in colon cancer (CC) with various tumor locations.Materials and methods. The study included 50 patients with CC. All patients underwent surgery as the primary treatment, and tissue material was collected from the patients. Expression of TLRs (2, 3, 4, 8, 9) on CD45+, CD45- cell populations was determined by flow cytometry in cell suspensions obtained from tissues of the tumor, peritumoral area (1–3 cm from the tumor) and resection line tissues (~10 cm from the tumor) with further calculation of the percentage of cells with the corresponding phenotype from the total number of cells.Results. An analysis of left-sided colon tumors showed lower percentage of CD45- cells expressing TLR4, 8, compared to rightsided tumors, by 38 % and 25 %. A comparative analysis of the number of CD45+ cells expressing TLR 2, 4 showed their decrease by 81 % and 87 %, respectively, compared with right-sided tumors. An assessment of the data in the perifocal zone of left-sided colon tumors, compared with right-sided ones, demonstrated a decrease in the percentage of cells with the CD45- phenotype that express TLR4, by 61 %. Resection line tissues in left-sided tumors, compared with right-sided ones, showed a statistically significant increase in the percentage of CD45- cells that express TLR 2, 4 by 205 % and 55 %, respectively. The number of CD45+ cells expressing TLR 4 decreased by 87 %. An assessment of the number of cells expressing TLRs 3 and 9 in the tumor, peritumoral area and resection line tissues did not reveal significant differences.Conclusions. Lower number of cells with CD45+ and CD45- phenotypes express TLRs 2, 4, 8 in left-sided colon tumors and their peritumoral tissues, compared to right-sided cancer.
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Simińska, Donata, Jan Korbecki, Klaudyna Kojder, Dariusz Jeżewski, Maciej Tarnowski, Patrycja Tomasiak, Katarzyna Piotrowska et al. "Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model". International Journal of Molecular Sciences 23, n. 21 (27 ottobre 2022): 13004. http://dx.doi.org/10.3390/ijms232113004.

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Glioblastoma multiforme (GBM) is a malignant glioma, difficult to detect and with the lowest survival rates among gliomas. Its greater incidence among men and its higher survival rate among premenopausal women suggest that it may be associated with the levels of androgens. As androgens stimulate the androgen receptor (AR), which acts as a transcription factor, the aim of this study was the investigate the role of AR in the progression of GBM. The study was conducted on tissues collected from three regions of GBM tumors (tumor core, enhancing tumor region, and peritumoral area). In addition, an in vitro experiment was conducted on U-87 cells under various culture conditions (necrotic, hypoxic, and nutrient-deficient), mimicking the conditions in a tumor. In both of the models, androgen receptor expression was determined at the gene and protein levels, and the results were confirmed by confocal microscopy and immunohistochemistry. AR mRNA expression was higher under nutrient-deficient conditions and lower under hypoxic conditions in vitro. However, there were no differences in AR protein expression. No differences in AR mRNA expression were observed between the tested tumor structures taken from patients. No differences in AR mRNA expression were observed between the men and women. However, AR protein expression in tumors resected from patients was higher in the enhancing tumor region and in the peritumoral area than in the tumor core. In women, higher AR expression was observed in the peritumoral area than in the tumor core. AR expression in GBM tumors did not differ significantly between men and women, which suggests that the higher incidence of GBM in men is not associated with AR expression. In the group consisting of men and women, AR expression varied between the regions of the tumor: AR expression was higher in the enhancing tumor region and in the peritumoral area than in the tumor core, showing a dependence on tumor conditions (hypoxia and insufficient nutrient supply).
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Pastushenko, Ievgenia, Tamara Gracia-Cazaña, Sandra Vicente-Arregui, Gert G. Van den Eynden, Mariano Ara, Peter B. Vermeulen, Franciso José Carapeto e Steven J. Van Laere. "Squamous Cell Carcinomas of the Skin Explore Angiogenesis-Independent Mechanisms of Tumour Vascularization". Journal of Skin Cancer 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/651501.

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Aims.To evaluate the vascularization in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin.Methods.We performed CD31 (i.e., panendothelial marker) and CD105 (i.e., proliferating endothelium marker) immunostaining on samples of 70 SCCs and 70 BCCs of the skin. We evaluated the relative blood vessel area using the Chalkley counting method in each histologic subtype of these tumours. We calculated the degree of proliferation of blood vessel endothelium dividing CD105-Chalkley score by CD31-Chalkley score.Results.We found significantly higher peritumoral and intratumoral blood vessel area in SCC when compared to BCC (both with CD31 and CD105). Chalkley counts differed significantly between groups with different BCC histologic subtypes and SCC with different grade of differentiation. Surprisingly, the degree of proliferation of blood vessel endothelium was higher in BCC when compared to SCC.Conclusions.While SCC exhibited significantly higher intratumoral and peritumoral blood vessel areas compared to BCC, the relatively low rate of proliferating endothelium in this tumour type suggests the existence of endothelial-sprouting-independent mechanisms of vascularization in SCC.
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Cepeda, Santiago, Luigi Tommaso Luppino, Angel Pérez-Núñez, Ole Solheim, Sergio García-García, María Velasco-Casares, Anna Karlberg et al. "Predicting Regions of Local Recurrence in Glioblastomas Using Voxel-Based Radiomic Features of Multiparametric Postoperative MRI". Cancers 15, n. 6 (22 marzo 2023): 1894. http://dx.doi.org/10.3390/cancers15061894.

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The globally accepted surgical strategy in glioblastomas is removing the enhancing tumor. However, the peritumoral region harbors infiltration areas responsible for future tumor recurrence. This study aimed to evaluate a predictive model that identifies areas of future recurrence using a voxel-based radiomics analysis of magnetic resonance imaging (MRI) data. This multi-institutional study included a retrospective analysis of patients diagnosed with glioblastoma who underwent surgery with complete resection of the enhancing tumor. Fifty-five patients met the selection criteria. The study sample was split into training (N = 40) and testing (N = 15) datasets. Follow-up MRI was used for ground truth definition, and postoperative structural multiparametric MRI was used to extract voxel-based radiomic features. Deformable coregistration was used to register the MRI sequences for each patient, followed by segmentation of the peritumoral region in the postoperative scan and the enhancing tumor in the follow-up scan. Peritumoral voxels overlapping with enhancing tumor voxels were labeled as recurrence, while non-overlapping voxels were labeled as nonrecurrence. Voxel-based radiomic features were extracted from the peritumoral region. Four machine learning-based classifiers were trained for recurrence prediction. A region-based evaluation approach was used for model evaluation. The Categorical Boosting (CatBoost) classifier obtained the best performance on the testing dataset with an average area under the curve (AUC) of 0.81 ± 0.09 and an accuracy of 0.84 ± 0.06, using region-based evaluation. There was a clear visual correspondence between predicted and actual recurrence regions. We have developed a method that accurately predicts the region of future tumor recurrence in MRI scans of glioblastoma patients. This could enable the adaptation of surgical and radiotherapy treatment to these areas to potentially prolong the survival of these patients.
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Granata, Vincenza, Roberta Fusco, Mario Sansone, Roberto Grassi, Francesca Maio, Raffaele Palaia, Fabiana Tatangelo et al. "Magnetic resonance imaging in the assessment of pancreatic cancer with quantitative parameter extraction by means of dynamic contrast-enhanced magnetic resonance imaging, diffusion kurtosis imaging and intravoxel incoherent motion diffusion-weighted imaging". Therapeutic Advances in Gastroenterology 13 (gennaio 2020): 175628481988505. http://dx.doi.org/10.1177/1756284819885052.

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Background: Despite great technical advances in imaging, such as multidetector computed tomography and magnetic resonance imaging (MRI), diagnosing pancreatic solid lesions correctly remains challenging, due to overlapping imaging features with benign lesions. We wanted to evaluate functional MRI to differentiate pancreatic tumors, peritumoral inflammatory tissue, and normal pancreatic parenchyma by means of dynamic contrast-enhanced MRI (DCE-MRI)-, diffusion kurtosis imaging (DKI)-, and intravoxel incoherent motion model (IVIM) diffusion-weighted imaging (DWI)-derived parameters. Methods: We retrospectively analyzed 24 patients, each with histopathological diagnosis of pancreatic tumor, and 24 patients without pancreatic lesions. Functional MRI was acquired using a 1.5 MR scanner. Peritumoral inflammatory tissue was assessed by drawing regions of interest on the tumor contours. DCE-MRI, IVIM and DKI parameters were extracted. Nonparametric tests and receiver operating characteristic (ROC) curves were calculated. Results: There were statistically significant differences in median values among the three groups observed by Kruskal–Wallis test for the DKI mean diffusivity (MD), IVIM perfusion fraction (fp) and IVIM tissue pure diffusivity (Dt). MD had the best results to discriminate normal pancreas plus peritumoral inflammatory tissue versus pancreatic tumor, to separate normal pancreatic parenchyma versus pancreatic tumor and to differentiate peritumoral inflammatory tissue versus pancreatic tumor, respectively, with an accuracy of 84%, 78%, 83% and area under ROC curve (AUC) of 0.85, 0.82, 0.89. The findings were statistically significant compared with those of other parameters ( p value < 0.05 using McNemar’s test). Instead, to discriminate normal pancreas versus peritumoral inflammatory tissue or pancreatic tumor and to differentiate normal pancreatic parenchyma versus peritumoral inflammatory tissue, there were no statistically significant differences between parameters’ accuracy ( p > 0.05 at McNemar’s test). Conclusions: Diffusion parameters, mainly MD by DKI, could be helpful for the differentiation of normal pancreatic parenchyma, perilesional inflammation, and pancreatic tumor.
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Zhong, Shiling, Fan Wang, Zhiying Wang, Minghui Zhou, Chunli Li e Jiandong Yin. "Multiregional Radiomic Signatures Based on Functional Parametric Maps from DCE-MRI for Preoperative Identification of Estrogen Receptor and Progesterone Receptor Status in Breast Cancer". Diagnostics 12, n. 10 (21 ottobre 2022): 2558. http://dx.doi.org/10.3390/diagnostics12102558.

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Radiomics based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been used for breast estrogen receptor (ER) and progesterone receptor (PR) status evaluation. However, the radiomic features of peritumoral regions were not thoroughly analyzed. This study aimed to establish and validate the multiregional radiomic signatures (RSs) for the preoperative identification of the ER and PR status in breast cancer. A total of 443 patients with breast cancer were divided into training (n = 356) and validation (n = 87) sets. Radiomic features were extracted from intra- and peritumoral regions on six functional parametric maps from DCE-MRI. A two-sample t-test, least absolute shrinkage and selection operator regression, and stepwise were used for feature selections. Three RSs for predicting the ER and PR status were constructed using a logistic regression model based on selected intratumoral, peritumoral, and combined intra- and peritumoral radiomic features. The area under the receiver operator characteristic curve (AUC) was used to assess the discriminative performance of three RSs. The AUCs of intra- and peritumoral RSs for identifying the ER status were 0.828/0.791 and 0.755/0.733 in the training and validation sets, respectively. For predicting the PR status, intra- and peritumoral RSs resulted in AUCs of 0.816/0.749 and 0.806/0.708 in the training and validation sets, respectively. Multiregional RSs achieved the best AUCs among three RSs for evaluating the ER (0.851 and 0.833) and PR (0.848 and 0.763) status. In conclusion, multiregional RSs based on functional parametric maps from DCE-MRI showed promising results for preoperatively evaluating the ER and PR status in breast cancer patients. Further studies using a larger cohort from multiple centers are necessary to confirm the reliability of the established models before clinical application.
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Youk, Ji Hyun, Eun Ju Son, Kyunghwa Han, Hye Mi Gweon e Jeong-Ah Kim. "Performance of shear-wave elastography for breast masses using different region-of-interest (ROI) settings". Acta Radiologica 59, n. 7 (23 ottobre 2017): 789–97. http://dx.doi.org/10.1177/0284185117735562.

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Background Various size and shape of region of interest (ROI) can be applied for shear-wave elastography (SWE). Purpose To investigate the diagnostic performance of SWE according to ROI settings for breast masses. Material and Methods To measure elasticity for 142 lesions, ROIs were set as follows: circular ROIs 1 mm (ROI-1), 2 mm (ROI-2), and 3 mm (ROI-3) in diameter placed over the stiffest part of the mass; freehand ROIs drawn by tracing the border of mass (ROI-M) and the area of peritumoral increased stiffness (ROI-MR); and circular ROIs placed within the mass (ROI-C) and to encompass the area of peritumoral increased stiffness (ROI-CR). Mean (Emean), maximum (Emax), and standard deviation (ESD) of elasticity values and their areas under the receiver operating characteristic (ROC) curve (AUCs) for diagnostic performance were compared. Results Means of Emean and ESD significantly differed between ROI-1, ROI-2, and ROI-3 ( P < 0.0001), whereas means of Emax did not ( P = 0.50). For ESD, ROI-1 (0.874) showed a lower AUC than ROI-2 (0.964) and ROI-3 (0.975) ( P < 0.002). The mean ESD was significantly different between ROI-M and ROI-MR and between ROI-C and ROI-CR ( P < 0.0001). The AUCs of ESD in ROI-M and ROI-C were significantly lower than in ROI-MR ( P = 0.041 and 0.015) and ROI-CR ( P = 0.007 and 0.004). Conclusion Shear-wave elasticity values and their diagnostic performance vary based on ROI settings and elasticity indices. Emax is recommended for the ROIs over the stiffest part of mass and an ROI encompassing the peritumoral area of increased stiffness is recommended for elastic heterogeneity of mass.
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Vajkoczy, Peter, Lothar Schilling, Axel Ullrich, Peter Schmiedek e Michael D. Menger. "Characterization of Angiogenesis and Microcirculation of High–Grade Glioma: An Intravital Multifluorescence Microscopic Approach in the Athymic Nude Mouse". Journal of Cerebral Blood Flow & Metabolism 18, n. 5 (maggio 1998): 510–20. http://dx.doi.org/10.1097/00004647-199805000-00006.

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The current study follows angiogenesis and microcirculatory changes associated with malignant glioma growth by means of an intravital fluorescence microscopic approach, which allows for the direct and continuous visualization of the glioma microvasculature and its quantitative analysis. Fluorescently labeled C6 rat glioma cells (5 × 105) were implanted into dorsal skinfold chamber preparations of athymic nude mice. Glioma growth, vascularization, microhemodynamics, vascular permeability, and leukocyte–endothelial cell interactions were simultaneously followed over a 22-day observation period using intravital epiillumination microscopy and a multifluorescent labeling technique. Analysis of the process of glioma vascularization revealed three stages with distinct microvascular characteristics: avascular stage (days 0 to 6), lag of glioma growth but initial glioma-induced angiogenesis within the host tissue in peritumoral areas; early vascular stage (days 6 to 14), glioma cell proliferation associated with a spatially homogeneous development of a glioma microvasculature; and late vascular stage (days 14 to 22), exponential tumor growth and expansion (> 400 mm3) with high vascular densities in the peritumoral region and reduced vascularization (microvascular perfusion) in the glioma center. Within the center, the functional vessel length per area correlated inversely with glioma size ( P<0.01). In the peritumoral region, functional vessel length per area was independent of glioma size, indicating persistent, high angiogenic activity throughout the observation period. Thus, the microvasculature of mature gliomas revealed a microvascular zonal division with a progressive reduction of the functional vessel length per area within the tumor center. The perfusion failure of individual microvessels within the glioma center was partly compensated by an increase of diameters ( P<0.05), and thus by an increase of blood flow in these functional microvessels ( P<0.05) over time. Histologic analysis demonstrated both expanding and infiltrating growth patterns, as well as focal necroses on day 22. These are the first data from repeated in vivo analysis of glioma growth, vascularization, and microcirculation.
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Yang, Wenbin, Sen Jiang, Jianbang Lin e Yangkang Li. "CT findings predict survival of patients with peripheral T cell lymphoma: a preliminary study". Radiology and Oncology 53, n. 1 (19 gennaio 2019): 31–38. http://dx.doi.org/10.2478/raon-2019-0005.

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Abstract Background Peripheral T-cell lymphoma (PTCL) is an uncommon disease with poor clinical outcomes. Radiological reports on the survival of patients with PTCL are scarce. The purpose of this study is to investigate the prognostic value of CT findings to predict clinical outcomes in fifty-one patients with histologically proven PTCL. Patients and methods The clinical data and CT images of all patients were retrospectively reviewed. CT features including number of involvement sites, lesion size, shape, margin, density, peritumoral invasion, intratumoral necrosis, lymph node involvement, and degree of contrast enhancement were evaluated. Univariate and multiple logistic regression analysis were used to determine the association between the clinical outcome and radiologic factors. Results Multiple site involvement, an ill-defined margin with peritumoral invasion, inhomogeneous density, and intratumoral necrosis were found to be associated with poor outcomes in univariate analysis (P < 0.05). An ill-defined margin with peritumoral invasion, was identified as an independent risk sign by further multivariate logistic regression analysis (P < 0.05). The area under the ROC curve of this CT feature was 0.745 (P < 0.05). Conclusions An ill-defined margin with peritumoral invasion was a valuable prognostic factor to predict the worse clinical outcomes in patients with PTCL.
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Bova, F. S., O. I. Kit, A. Yu Maksimov e N. S. Karnaukhov. "Modification of biochemical recurrence risk in patients with localized prostate cancer after radical prostatectomy with combined histomorphological changes in the peritumoral zone". Kazan medical journal 99, n. 3 (15 giugno 2018): 408–15. http://dx.doi.org/10.17816/kmj2018-408.

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Aim. To assess the prognostic significance of histopathological processes in the peritumoral zone with respect to the risk of biochemical recurrence in patients with localized prostate cancer after radical prostatectomy. Methods. Histomorphological studies were conducted in the perifocal area of surgical tissue samples from 309 patients with localized prostate cancer (T1c-2cN0M0) after a radical surgery using light microscopy. Four groups of patients were identified depending on the risk of recurrence. Enzyme immunoassay was used to determine the concentration of prostate-specific antigen in the serum at baseline and every 3 months for two years after the surgery to detect biochemical recurrence. Results. Histomorphological examination of the peritumoral zone made it possible to identify histopathological processes associated with adenocarcinoma in 257 out of 309 (83.2%) patients with localized prostate cancer. The risk of biochemical recurrence of a combination of prostatic adenocarcinoma and prostatic intraepithelial neoplasia-2 increased by 3.3 (p=0.02), and of a combination of adenocarcinoma, neoplasia and chronic inflammation in the perifocal zone increased by 4.5 times (p=0.005) compared to patients without histopathological changes of the peritumoral zone. In combination of prostate adenocarcinoma with neoplasia and chronic inflammation in the peritumoral zone, the number of patients with an intermediate risk of cancer recurrence after surgical treatment increased due to decrease of the proportion of patients with very low and low risk of recurrence of the oncologic disease. Conclusion. The combination of prostate cancer with high-grade prostatic intraepithelial neoplasia and chronic inflammation in the peritumoral zone modifies the risk of biochemical recurrence of cancer after radical prostatectomy.
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Surhonne, Sharmila P., Sahithi Tadi, Shushan S. Jayker e Jyothi R. Kaluva. "Spectrum of Lesions in Peritumoral Area in Association with Carcinoma of Breast". Journal of Medical Sciences 5, n. 3 (2019): 63–66. http://dx.doi.org/10.5005/jp-journals-10045-00130.

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Tamura, Ryota, Kentaro Ohara, Hikaru Sasaki, Yukina Morimoto, Kenzo Kosugi, Kazunari Yoshida e Masahiro Toda. "Difference in Immunosuppressive Cells Between Peritumoral Area and Tumor Core in Glioblastoma". World Neurosurgery 120 (dicembre 2018): e601-e610. http://dx.doi.org/10.1016/j.wneu.2018.08.133.

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Beig Zali, Sanaz, Farbod Alinezhad, Mahnaz Ranjkesh, Mohammad H. Daghighi e Masoud Poureisa. "Accuracy of apparent diffusion coefficient in differentiation of glioblastoma from metastasis". Neuroradiology Journal 34, n. 3 (8 gennaio 2021): 205–12. http://dx.doi.org/10.1177/1971400920983678.

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Background Brain metastasis and glioblastoma multiforme are two of the most common malignant brain neoplasms. There are many difficulties in distinguishing these diseases from each other. Purpose The purpose of this study was to determine whether the mean apparent diffusion coefficient and absolute standard deviation derived from apparent diffusion coefficient measurements can be used to differentiate glioblastoma multiforme from brain metastasis based on cellularity levels. Material and methods Magnetic resonance images of 34 patients with histologically verified brain tumors were evaluated retrospectively. Apparent diffusion coefficient and standard deviation values were measured in the enhancing tumor, peritumoral region, and contralateral healthy white matter. Then, to determine whether there was a statistical difference between brain metastasis and glioblastoma multiforme, we analyzed different variables between the two groups. Results Neither mean apparent diffusion coefficient values and ratios nor standard deviation values and ratios were significantly different between glioblastoma multiforme and brain metastasis. Receiver operating characteristic curve analysis of the logistic model with backward stepwise feature selection yielded an area under the curve of 0.77, a specificity of 84%, a sensitivity of 67%, a positive predictive value of 83.33%, and a negative predictive value of 78.26% for distinguishing between glioblastoma multiforme and brain metastasis. The absolute standard deviation and standard deviation ratios were significantly higher in the peritumoral edema compared to the tumor region in each case. Conclusion Apparent diffusion coefficient values and ratios, as well as standard deviation values and ratios in peritumoral edema, cannot be used to differentiate edema with infiltration of tumor cells from vasogenic edema. However, standard deviation values could successfully characterize areas of peritumoral edema from the tumoral region in each case.
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Wang, Jili, Shanshan Qu, Qinyan Xu, Zhaofeng Jin, Tian Li, Shuxian Zhang e Xihe Sun. "Correlation Analysis between Retention of Gd-DTPA in the Cystic Area of Brain Metastasis and MRI Signs". Journal of Oncology 2022 (18 giugno 2022): 1–7. http://dx.doi.org/10.1155/2022/2738892.

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Objective. The aim of this study is to investigate gadolinium-diethylenetriaminepentacetate (Gd-DTPA) retention in the cystic area of brain metastasis and its correlation with MRI signs. Methods. Clinical and MRI data of 76 patients with brain metastasis in the cystic area were collected. The contrast signal intensity (CSI) of the cystic area and edema area in the plain scan, enhanced scan, and plain scan after enhancement within 1 month (hereafter referred to as “enhanced plain scan”) were analyzed to determine whether Gd-DTPA was retained in these areas. The lesions with higher CSI values on the enhanced plain scan were classified as the Gd-DTPA retention group and the remaining lesions as the Gd-DTPA-free group. The two groups were compared to determine significant differences in primary lesion type, tumor size, tumor location, capsule wall thickness and morphology, peritumoral edema, and renal function. Results. A total of 123 lesions were detected. The CSI of the enhanced plain scan exceeded that of the plain scan and enhanced scan in the cystic area ( P < 0.05 ). There were 54 lesions (43.9%) with Gd-DTPA retention in the cystic area and 69 lesions (56.1%) without Gd-DTPA retention. Significant differences were observed in tumor size and cystic wall thickness between the two groups ( P < 0.05 ), while no significant differences in primary lesion type, cystic wall shape, peritumoral edema, or function were observed. Conclusion. The retention of Gd-DTPA was found in the cystic area of some brain metastases, which was correlated with tumor size and cystic wall thickness.
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Annese, Tiziana, Mariella Errede, Antonio d’Amati, Michelina De Giorgis, Loredana Lorusso, Roberto Tamma e Domenico Ribatti. "Differential P-Glycoprotein/CD31 Expression as Markers of Vascular Co-Option in Primary Central Nervous System Tumors". Diagnostics 12, n. 12 (10 dicembre 2022): 3120. http://dx.doi.org/10.3390/diagnostics12123120.

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Background: Vascular co-option is one of the main features of brain tumor progression. It is identified using histopathological analysis, but no antibody-specific markers were found, and no universally accepted histological features were defined. Methods: We employed double immunohistochemical stainings for CD31, P-gp, S100A10, and mitochondria on formalin-fixed, paraffin-embedded human samples of IDH-WT glioblastoma, IDH-mutant astrocytoma, and meningioma to study vascular co-option across different brain tumors and across normal, peritumoral, and intratumoral areas using the Aperio colocalization algorithm, which is a valid and robust method to handle and investigate large data sets. Results: The results have shown that (i) co-opted vessels could be recognized by the presence of metabolically overactive (evaluated as mitochondria expression) and P-gp+ or S100A10+ tumor cells surrounding CD31+ endothelial cells; (ii) vascular co-option occurs in the intratumoral area of meningioma and astrocytoma; and (iii) vascular co-option is prevalent in peritumoral glioblastoma area. Conclusions: The described approach identifies new markers for cellular components of the vessel wall and techniques that uncover the order and localization of vascularization mechanisms, which may contribute to developing new and possibly more effective therapeutic strategies.
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Zhao, Jian-Lan, Bo Tan, Gong Chen, Xiao-Ming Che, Zhuo-Ying Du, Qiang Yuan, Jian Yu et al. "Hypoxia-Induced Glioma-Derived Exosomal miRNA-199a-3p Promotes Ischemic Injury of Peritumoral Neurons by Inhibiting the mTOR Pathway". Oxidative Medicine and Cellular Longevity 2020 (13 ottobre 2020): 1–12. http://dx.doi.org/10.1155/2020/5609637.

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The underlying molecular mechanisms that the hypoxic microenvironment could aggravate neuronal injury are still not clear. In this study, we hypothesized that the exosomes, exosomal miRNAs, and the mTOR signaling pathway might be involved in hypoxic peritumoral neuronal injury in glioma. Multimodal radiological images, HE, and HIF-1α staining of high-grade glioma (HGG) samples revealed that the peritumoral hypoxic area overlapped with the cytotoxic edema region and directly contacted with normal neurons. In either direct or indirect coculture system, hypoxia could promote normal mouse hippocampal neuronal cell (HT22) injury, and the growth of HT22 cells was suppressed by C6 glioma cells under hypoxic condition. For administrating hypoxia-induced glioma-derived exosomes (HIGDE) that could aggravate oxygen-glucose deprivation (OGD)/reperfusion neuronal injury, we identified that exosomes may be the communication medium between glioma cells and peritumoral neurons, and we furtherly found that exosomal miR-199a-3p mediated the OGD/reperfusion neuronal injury process by suppressing the mTOR signaling pathway. Moreover, the upregulation of miRNA-199a-3p in exosomes from glioma cells was induced by hypoxia-related HIF-1α activation. To sum up, hypoxia-induced glioma-derived exosomal miRNA-199a-3p can be upregulated by the activation of HIF-1α and is able to increase the ischemic injury of peritumoral neurons by inhibiting the mTOR pathway.
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Kousi, E., I. Tsougos, E. Tsolaki, K. N. Fountas, K. Theodorou, I. Fezoulidis, E. Kapsalaki e C. Kappas. "Spectroscopic Evaluation of Glioma Grading at 3T: The Combined Role of Short and Long TE". Scientific World Journal 2012 (2012): 1–11. http://dx.doi.org/10.1100/2012/546171.

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Purpose. To evaluate the diagnostic value of 3T1H-MRS in grading cerebral gliomas using short and long echo times.Methods. 1H-MRS was performed on 71 patients with untreated cerebral gliomas. Metabolite ratios of NAA/Cr, Cho/Cr, Cho/NAA, and mI/Cr were calculated for short and long TE and compared between low and high grade gliomas. Lipids were qualitatively evaluated. ROC analysis was performed to obtain the cut-off values for the metabolic ratios presenting statistical difference between the two glioma grades.Results. Intratumoral Cho/Cr at both TEs and long TE Cho/NAA were significantly different between low and high grade gliomas. Peritumoral NAA/Cr of both TEs, as well as long TE Cho/Cr and Cho/NAA ratios, significantly differentiated the two tumor grades. Diagnostic sensitivity of peritumoral short TE NAA/Cr proved to be superior over the other metabolic ratios, whereas intratumoral short TE Cho/Cr reached the highest levels of specificity and accuracy. Overall, short TE 1H-MRS reached higher total sensitivity in predicting glioma grade, over long TE.Conclusion. An advantage was found in using short TE over long TE 1H-MRS in the discrimination of low versus high grade gliomas. Moreover, the results suggested that the peritumoral area of gliomas may be more valuable in predicting glioma grade than using only the intratumoral area.
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Ghinda, Diana C., Yufei Yang, Shuai Wu, Junfeng Lu, Lan Su, Stefano Damiani, Shankar Tumati et al. "Personalized Multimodal Demarcation of Peritumoral Tissue in Glioma". JCO Precision Oncology, n. 4 (settembre 2020): 1128–40. http://dx.doi.org/10.1200/po.20.00115.

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PURPOSE Gliomas are life-threatening brain tumors, and the extent of surgical resection is one of the strongest influences on survival rate. However, the proper distinction of infiltrated tissue remains elusive. The aim of this study was to use multimodal analyses to demarcate peritumoral tissue (PT) from tumoral (TT) and healthy tissue (HT). METHODS A total of 40 patients with histologically confirmed glioma were recruited. We analyzed resting-state functional magnetic resonance imaging (rs-fMRI) using the voxel-based mean blood-oxygen-level-dependent (BOLD) signal and the corresponding structural MRI (s-MRI) alongside RNA sequencing, whole-exome sequencing, and histology results of biopsy samples obtained from PT, HT, and TT. RESULTS We demarcated a functionally defined PT area where the mean BOLD signal gradually decreased near the edge of the tumor and extended beyond the TT borders (as defined by s-MRI), which was confirmed on a case-by-case basis. Correspondingly, genetic analyses showed a gene expression pattern and mutational landscape of the PT that were distinct from that seen in HT and TT. The genetic characterization of PT relative to HT and TT converged with the MRI-defined PT zones. This was confirmed in three individual cases after additional histologic analysis. A wider PT was associated with a longer progression-free survival, which suggests PT might act as an intermediate area between TT and HT. CONCLUSION Combined multimodal imaging and genetic analyses can allow for an objective demarcation of the PT in glioma and a robust classification of the degree of infiltration of the PT. These findings could help improve both neurosurgical resection and radio-oncologic therapy.
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Shiinoki, Takehiro, Koya Fujimoto, Yusuke Kawazoe, Yuki Yuasa, Miki Kajima, Yuki Manabe, Taiki Ono, Tsunahiko Hirano, Kazuto Matsunaga e Hidekazu Tanaka. "Predicting programmed death-ligand 1 expression level in non-small cell lung cancer using a combination of peritumoral and intratumoral radiomic features on computed tomography". Biomedical Physics & Engineering Express 8, n. 2 (1 febbraio 2022): 025008. http://dx.doi.org/10.1088/2057-1976/ac4d43.

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Abstract In this study, we investigated the possibility of predicting expression levels of programmed death-ligand 1 (PD-L1) using radiomic features of intratumoral and peritumoral tumors on computed tomography (CT) images. We retrospectively analyzed 161 patients with non-small cell lung cancer. We extracted radiomic features for intratumoral and peritumoral regions on CT images. The null importance, least absolute shrinkage, and selection operator model were used to select the optimized feature subset to build the prediction models for the PD-L1 expression level. LightGBM with five-fold cross-validation was used to construct the prediction model and evaluate the receiver operating characteristics. The corresponding area under the curve (AUC) was calculated for the training and testing cohorts. The proportion of ambiguously clustered pairs was calculated based on consensus clustering to evaluate the validity of the selected features. In addition, Radscore was calculated for the training and test cohorts. For expression level of PD-L1 above 1%, prediction models that included radiomic features from the intratumoral region and a combination of radiomic features from intratumoral and peritumoral regions yielded an AUC of 0.83 and 0.87 and 0.64 and 0.74 in the training and test cohorts, respectively. In contrast, the models above 50% prediction yielded an AUC of 0.80, 0.97, and 0.74, 0.83, respectively. The selected features were divided into two subgroups based on PD-L1 expression levels≥50% or≥1%. Radscore was statistically higher for subgroup one than subgroup two when radiomic features for intratumoral and peritumoral regions were combined. We constructed a predictive model for PD-L1 expression level using CT images. The model using a combination of intratumoral and peritumoral radiomic features had a higher accuracy than the model with only intratumoral radiomic features.
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Sheiko, A. V. "Target Volume Delineation for Radiation Therapy of High-Grade Gliomas". Journal of oncology: diagnostic radiology and radiotherapy 3, n. 4 (31 dicembre 2020): 18–25. http://dx.doi.org/10.37174/2587-7593-2020-3-4-18-25.

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High-grade gliomas are characterized by rapid growth, poor prognosis and frequent unsatisfactory treatment results. Radiation therapy remains one of the main methods of treatment of this disease. However, the question of choosing the optimal macroscopic (Gross Tumor Volume — GTV) and clinical (Clinical Target Volume — CTV) volumes in the planning of radiation treatment remains controversial. There are several approaches to the target volume delineation for radiotherapy of high-grade gliomas, depending on the peritumoral edema. There is no correlation between the frequency of recurrences and methods of delineation of gliomas. GTV should be defined as the area of enhancement on the post-contrast T1-weighted MRI, i.e. postoperative cavity and residual tumor. Peritumoral edema is an unreliable orienting point when contouring target volumes.
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Kostenikov, Nikolay, Violetta Dubrovskaya, Elena Kovanko, Olga Mirolyubova, Marina Mukhina, Yury Ilyushchenko, Andrei Stanzhevsky e Dmitry Maistrenko. "Glioma C6 perivascular changes of invasion structural parameters variation (research study)." Problems in oncology 67, n. 1 (4 marzo 2021): 144–49. http://dx.doi.org/10.37469/0507-3758-2021-67-1-144-149.

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A comparative study of the structural characteristics of microvessels with a perivascular arrangement of tumor cells and microvessels with normal structure located in the peritumoral zones of an intracranially implanted glioblastoma ("glioma C6") was conducted. The study was performed on rats. Morphometric method was used to determine the area, internal diameter and length of microvessels for 21 days after the introduction of tumor cells into the brain of rats. Changes in the structure of microvessels with glioblastoma cells were registered throughout the entire observation period. The active role of perivascularly located tumor cells in the transformation of the structure and properties of microvessels involved in the process of glioblastoma invasion into brain tissue is considered. Key words: glioblastoma, microvessels, morphometry, peritumoral zones.
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Zykova, Tatiana, Oleg Ivanovich Kit, Galina Andreevna Nerodo, Victoria A. Ivanova, Vera P. Nikitina, Ekaterina V. Verenikina, Oksana E. Kravtsova e Olga A. Bogomolova. "On Bacteroides Fragilis participation in vulvar carcinogenesis." Journal of Clinical Oncology 35, n. 15_suppl (20 maggio 2017): e17026-e17026. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17026.

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e17026 Background: The purpose of the study was to identify the rate of Bacteroides spp. infection in vulvar cancer tissues. Methods: FFPE samples of tumor and peritumoral area and healthy tissues of 44 patients with vulvar cancer, as well as frozen tumor tissues of 34 cervical cancer and 29 uterine cancer patients were studied. DNAs of Bacteroides spp. were detected by real-time PCR. Results: 18.75% of patients had stage I disease, 75.0% - stage II, 6.25% - stage III. The analysis of tumor histological type showed squamous cell carcinoma: G1 - 31.25%, G2 - 68.75%. B. fragilis were found in all vulvar tissues: tumor tissue – in 87.5%, perifocal area – in 76.9% and healthy tissue – in 71.4% of patients. Bacteroids of other groups were not found. For comparison, B. fragilis DNAs were detected in 20.7% in uterine cancer and in 15.4% in cervical cancer. DNA amount in samples was assessed by the Ct value. This index is inversely proportional to the DNA amount in the sample. Mean Ct level in tumor tissue was 23.2, in peritumoral area – 23.7, and in healthy tissue – 26.1; so, the amount of B. fragilis DNAs was similar in tumor and peritumoral area and was lower in healthy tissues. Differences in bacterial contamination of tumor tissue were found between vulvar cancer, cervical and uterine cancer. The amount of B. fragilis DNAs was maximal in vulvar cancer. We did not establish clear relationships between the rate of B. fragilis infection in tumor and the disease stage, tumor grade and the rate of metastasis. Conclusions: B .fragilis infection was found in tissues of the entire vulva; however, the infection rate and bacterial contamination level were higher in tumor tissue compared to the perifocal area and healthy tissue. Tumor tissues in vulvar cancer were infected more often than in uterine and cervical cancers. Bacterial contamination level in tumor tissue was higher in vulvar cancer than in uterine and cervical cancers which was undoubtedly significant in vulvar cancer pathogenesis.

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