Vascular Aging in the Choroid Plexus: A 7T Ultrasmall Superparamagnetic Iron Oxide (USPIO)-MRI Study.

BACKGROUND: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP. PURPOSE: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels. STUDY TYPE: Prospective. SUBJECTS: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females). FIELD STRENGTH/SEQUENCE: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR. ASSESSMENT: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant. RESULTS: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45). DATA CONCLUSION: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

The anti-scarring role of Lycium barbarum polysaccharide on cornea epithelial-stromal injury.

PURPOSE: Cornea epithelial-stromal scarring is related to the differentiation of fibroblasts into opaque myofibroblasts. Our study aims to assess the effectiveness of Lycium barbarum polysaccharide (LBP) solution as a pre-treatment in minimizing corneal scarring. METHODS: Human corneal fibroblasts were cultured in a three-dimensional collagen type I-based hydrogel in an eye-on-a-chip model. Fibroblasts were pre-treated with 2 mg/mL LBP for 24 h, followed by another 24-h incubation with 10 ng/mL transforming growth factor-beta 1 (TGF-ß1) to induce relevant physiological events after stromal injury. Intracellular pro-fibrotic proteins, extracellular matrix proteins, and pro-inflammatory cytokines that involved in fibrosis, were assessed using immunocytochemistry and enzyme-linked immunosorbent assays. RESULTS: Compared to the positive control TGF-ß1 group, LBP pre-treated cells had a significantly lower expression of alpha-smooth muscle actin, marker of myofibroblasts, vimentin (p < 0.05), and also extracellular matrix proteins both collagen type II and type III (p < 0.05) that can be found in scar tissues. Moreover, LBP pre-treated cells had a significantly lower secretion of pro-inflammatory cytokines interleukin-6 and interleukin-8 (p < 0.05). The cell-laden hydrogel contraction and stiffness showed no significant difference between LBP pre-treatment and control groups. Fibroblasts pretreated with LBP as well had reduced angiogenic factors expression and suppression of undesired proliferation (p < 0.05). CONCLUSION: Our results showed that LBP reduced both pro-fibrotic proteins and pro-inflammatory cytokines on corneal injury in vitro. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option prior to corneal refractive surgeries with an improved prognosis.

[Surgical approach to resection of vestibular schwannomas following stereotactic radiological treatment. Surgical outcomes and morphological changes in tumors after radiotherapy]. / Khirurgicheskaia taktika pri udalenii vestibuliarnykh shvannom posle stereotaksicheskogo radiologicheskogo lecheniia. Rezul'taty operatsii i morfologicheskie izmeneniia v opukholiakh posle oblucheniia.

INTRODUCTION: Radiation therapy of small vestibular schwannomas is quite often used as an effective alternative to surgical treatment. At the same time, 2-10% of patients are detected with radioresistant tumors progressing to varying degrees, which is associated with continued tumor growth. In these cases, a decision on surgical resection or re-irradiation of the tumor is made depending on the neurological symptoms, patient's somatic status, and neuroimaging data. Surgical outcomes and intraoperative findings in pre-irradiated patients have been poorly represented in the literature, for which reason we decided to conduct this study. The paper presents a series of patients with vestibular schwannomas who underwent surgical removal of the tumor after radiotherapy. MATERIAL AND METHODS: A total of 39 patients with vestibular schwannomas after radiotherapy underwent surgery at the Burdenko Neurosurgical Institute in 2007-2017. Of these, 22 patients had a tumor removed after a previously performed combined surgical and radiotherapy treatment (group I), and 17 patients underwent tumor resection after previous radiological treatment (group II). The surgical outcomes were studied depending on various factors, and an analysis of the morphological changes in vestibular schwannomas after radiological treatment was carried out. RESULTS: In group I, the tumor was resected totally in 18% of patients, almost totally in 5% of patients, subtotally in 68% of patients, and partially in 9% of patients. In group II, the tumor was resected totally in 6% of patients, almost totally in 12% of patients, subtotally in 76% of patients, and partially in 6% of patients. We found that post-radiation changes in patients undergoing surgery led to an increase in the response of neurovascular structures to surgical intervention, development of pronounced fibrosis around tumors, and changes in the structure of tumors that became more solid. As a result, surgical morbidity increased, and the patient's quality of life after surgery deteriorated.

Can tumour budding change the future of pulmonary adenocarcinoma?

BACKGROUND: Pulmonary adenocarcinoma shows different prognosis even in the same pathological subtype and stage. In this study, it is aimed to investigate the relationship between tumour budding and known prognostic values and clinicopathological features in pulmonary adenocarcinoma. METHODS: In this study, there have been 77 patients diagnosed with primary pulmonary adenocarcinoma. In the evaluation process, the number of budding between 0 and 4 is accepted as low budding (Bd1), the number of budding between 5 and 9 is considered as medium budding (Bd2), and the number of budding above 10 is considered as high budding (Bd3). RESULTS: According to the findings of the study, it can be seen that there is a statistical difference between tumour budding and stromal fibrosis (p < 0.001). The presence of pleural invasion, lymph vascular invasion and perineural invasion in patients with Bd3 is found to be statistically higher than the patients with Bd1 (p = 0.048) (p = 0.041) (p = 0.029). CONCLUSIONS: Tumour budding has been associated with pleural invasion, lymph vascular invasion, perineural invasion, and stromal fibrosis. This study is the first to show the relationship between tumour budding and stromal fibrosis in pulmonary adenocarcinomas. The role of tumour budding in lung cancers remains to be clarified.

Evaluation of Tumor Fibrosis in Pancreatic Ductal Adenocarcinoma by 2-D Shear Wave Elastography: A Pilot Study.

OBJECTIVE: The aim of the work described here was to investigate the association of the stromal proportion with the elasticity obtained by 2-D shear wave elastography (SWE) and the diagnostic value of elasticity in evaluating tumor stromal fibrosis in pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients who met inclusion criteria underwent pre-operative 2-D SWE examination and intra-operative determination of hardness by palpation from July 2021 to November 2022, and the post-operative specimens were used to evaluate pathological features including the tumor stromal proportion. A receiver operating characteristic curve was created to evaluate its diagnostic value in differentiating the degree of tumor stromal fibrosis. RESULTS: The 2-D SWE measurements in pancreatic lesions were successful in 62 of 69 patients (89.9%). A total of 52 eligible participants were enrolled for subsequent correlation analysis. Elasticity correlated well with tumor stromal proportion (rs = 0.646) and number of tumor cells (rs = -0.585) in PDAC. Moreover, pancreatic elasticity determined by 2-D SWE, palpation-determined hardness and tumor stromal proportion were well correlated with each other. Two-dimensional SWE could clearly distinguish mild and severe stromal fibrosis, and its diagnostic performance was better than that determined by palpation even though the difference was not statistically significant (p = 0.103). CONCLUSION: The elasticity of PDAC obtained using 2-D SWE was closely related to stromal proportion and tumor cellularity and could clearly be used to diagnose the degree of stromal fibrosis, which indicates that 2-D SWE can be a non-invasive predictive imaging biomarker in personalization of therapy and monitoring of treatment.

Smoking and Fibrocystic Changes in the Breast: A Case Report of a Lifelong Smoker and Changes in Breast Parenchyma.

Smoking is a well-known risk factor for breast cancer, and the nicotine in cigarette smoke has been associated with fibrotic changes in the breast. Although considered benign, these changes have the potential to make surgical dissection more difficult and may increase the risk of surgical complications. Here we discuss the case of a middle-aged female who was a lifelong smoker with breast cancer and who underwent a simple mastectomy. Intra-operatively, the overall breast parenchyma appeared quite firm, making tissue dissection challenging and the operating surgeon had to endure to remove the tumor and the remaining breast tissue.

Different Features of 18F-FAPI, 18F-FDG PET/CT and MRI in the Evaluation of Extrahepatic Metastases and Local Recurrent Hepatocellular Carcinoma (HCC): A Case Report and Review of the Literature.

Background: Recurrence and metastasis are important causes of postoperative death in most HCC patients. Conventional imaging modalities such as 18F-FDG PET/CT and enhanced MRI are still unsatisfactory in evaluating these patients in the clinical setting. PET/CT imaging with a radiolabeled fibroblast activation protein inhibitor (FAPI) has emerged as a new imaging technique for the diagnosis and radiotherapy of malignant tumors. While many studies have focused on the diagnostic accuracy of intrahepatic primary HCC, the evaluation of recurrent and metastatic HCC remains only poorly investigated. Case Presentation: A 71-year-old man with a five-year history of HCC after radical resection underwent 18F-FDG PET/CT due to further surgery for tumor recurrence, which revealed two iso-metabolic lesions in the right peritoneum and a hypo-metabolic lesion in the right liver. 18F-FAPI PET/CT was performed to further complement 18F-FDG PET/CT in the detection of these suspected metastatic lesions. Importantly, multiple diffuse intense radioactivity was shown in the hepatic capsule, suggesting metastatic lesions, but a wedge-shaped elevated 18F-FAPI uptake disorder around the FDG-unavid necrotic lesion after radiofrequency ablation (RFA) demonstrated benign stromal fibrosis. Conclusion: This case suggested that 18F-FAPI may have an advantage over 18F-FDG in detecting peritoneal metastasis even in tiny or early hepatic capsules of HCC, but its false positives due to postoperative stromal fibrosis should be noted. Wedge- or strip-shaped FAPI-avid lesions with sharp edges may be post-treatment stromal fibrosis.

Stromal Fibrosis of the Breast and the Associated Radiological Findings.

This case report follows a 42-year-old female patient who underwent a routine screening mammogram. The patient was found to have a 50 mm benign subareolar mass in the right breast. However, because benign imaging findings do not preclude malignancy, the patient was recommended to undergo a biopsy for confirmation. Subsequent imaging and core needle biopsy established a benign lesion consistent with stromal fibrosis with underlying fibroadenomatous changes. The benign imaging and histological findings of the breast mass were concordant. The patient was recommended yearly mammograms and continued observation. This case report highlights the importance of radiopathological concordance in patients found to have benign imaging findings on screening mammograms.

Advances in mechanism and regulatory factors of corneal stromal repair / 国际眼科杂志(Guoji Yanke Zazhi)

Corneal stromal is an important structure to maintain corneal transparency. The corneal stroma can be injured by trauma, infection and surgery. Therefore, corneal stromal wound starts repair with phenotype changes in stromal cell, extracellular matrix remodeling and immune cells migration. The corneal scar was the leading cause of blindness worldwide, which can be caused by corneal stromal fibrosis from increased myofibroblasts and deposited extracellular matrix after sever damage. At present, corneal transplantation is the main treatment for corneal scar, which has limited therapeutic effect because of corneal donor shortage, surgical requirements and the risk of postoperative immune rejection. Recently, great progress has been made in the study of control mechanism of corneal stromal wound healing with various molecules, cells and tissues. This paper reviews the repair mechanism of corneal stromal injury and the regulation mechanism of cause of corneal injury, corneal structure and molecule factors towards corneal stromal injury. It aims at providing new ideas for exploring the mechanism of corneal stromal repair and regeneration, which is supposed to help prevent corneal scar clinically.

A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment.

INTRODUCTION: There is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour. METHODS AND ANALYSIS: This is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed. ETHICS AND DISSEMINATION: The trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION: CT.gov identifier: NCT01765244 (Jan2013). EudraCT number: 2010-024290-40 (Dec2012).

Histopathological Features of Non-Neoplastic Breast Parenchyma Do Not Predict BRCA Mutation Status of Patients with Invasive Breast Cancer.

BACKGROUND: Several studies have evaluated histologic features of non-neoplastic breast parenchyma in patients with BRCA1/2 mutations, but the results are conflicting. The limited data suggest a much higher prevalence of high-risk precursor lesions in BRCA carriers. Therefore, we designed this study to compare the clinicopathological characteristics of peritumoral benign breast tissue in patients with and without deleterious BRCA mutations. METHODS: Women with breast cancer (BC) who were referred for genetic counseling and underwent BRCA genetic testing in 2010 and 2011 were included in the study. RESULTS: Of the six benign histological features analyzed in this study, only stromal fibrosis grade 2/3 was found to be statistically different, with more BRCA noncarriers having stromal fibrosis grade 2/3 than BRCA1/2 carriers (P = 0.04). CONCLUSION: There is no significant association between mutation risk and the presence of benign histologic features of peritumoral breast parenchyma.

Histopathological study of placentae in low birth weight babies in India.

BACKGROUND: The antenatal health-care given to pregnant women has great influence on the rates of perinatal death and morbidity. Amongst the different causes of perinatal mortality, low birth weight (LBW) is the single most significant factor therefore placenta from all the LBW babies (LBWB) should be examined routinely to find out the likely cause. AIMS: The aims of this study were to assess the pathological changes in the placenta in association with LBWB. MATERIALS AND METHODS: This is a Case control study performed at Medical College Allahabad,(MLN) India. In this study, 90 placentae were included. 30 placentae from full-term vaginally delivered babies, weighing more than 2500 g were included as the control group. 60 placentae belonged to babies whose birth weight was less than 2500 g (LBW). Weight of the baby was taken within the 1(st) h of birth and Apgar score was noted. Gross and microscopic examination of placentae was done. Statistical correlation of was carried out between them by using SPSS 18 version. Chi-square test with or without yate's correction was used as and when required. P < 0.05 was taken as critical level of significance. RESULTS: Placenta was circum-marginal in both groups. Attachment of cord was mainly central in the control group 90% (27/30), whereas eccentric attachment was prominent in patient group 66.67% (40/60). The difference was statistically significant (P < 0.001). Calcification and sub-chorionic fibrin deposition was seen in significantly higher numbers of placentae from patients than controls (P < 0.01) infarction and meconium staining were seen in placentae from patients only. Histologically placental ischemia, infarction and calcification were seen in significantly higher number of patients (P < 0.001, P < 0.001 and < 0.01 respectively). Fibrinoid necrosis, stromal fibrosis, placental dysmaturity and obstructive vasculopathy were seen in placentae from patients only. CONCLUSION: Placental pathology among LBW infants was high in comparison to control group. The findings suggest that chronic ischemia and associated secondary changes probably lead to improper perfusion and LBWB.