The Usefulness of Ultrasonography for Supporting the Differentiation, Diagnosis, and Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare histomorphological variants of a disease spectrum. After ruling out other tumor entities by immunohistochemistry, PDS can be differentiated from AFX by infiltration into the subcutis, while AFX remains confined to the dermis. The therapeutic approach is more aggressive in PDS as it can potentially metastasize. We assessed the usefulness of preoperative sonography in differentiating between the two tumor entities by identifying a potential subcutaneous infiltration. In our patients (n = 13), preoperative sonography identified and differentiated AFX and PDS with 100% accuracy and even changed the initial histological suspicion of AFX to PDS in 3 cases (23%), which was confirmed after tumor resection. Preoperative sonography of these tumors could strengthen the clinical diagnosis, avoid a delay in therapy initiation and improve patient counseling. While for AFX, micrographic-controlled surgery suffices, for PDS, resection with 2 cm safety margins and lymph node sonography to rule out lymphonodal involvement is necessary. Hence, ultrasonography can improve clinical practice by providing helpful information for dermatosurgeons, which cannot be obtained during clinical examination.

Recent Trends in Adipose Tissue-Derived Injectable Therapies for Osteoarthritis: A Scoping Review of Animal Models.

Background and Objectives: This scoping review investigates recent trends in adipose tissue-derived injectable therapies for osteoarthritis (OA) in animal models, focusing on minimally manipulated or lightly processed adipose tissue. By evaluating and examining the specific context in which these therapies were investigated across diverse animal OA models, this review aims to provide valuable insights that will inform and guide future research and clinical applications in the ongoing pursuit of effective treatments for osteoarthritis. Materials and Methods: This research conducted a comprehensive literature review of PubMed and Embase to determine studies about minimally manipulated adipose tissue-derived injectable therapies for osteoarthritis investigated using animal models. The primary search found 530 results. After excluding articles that focused on spontaneous osteoarthritis; on transfected, preconditioned, cultured, or co-cultured adipose-derived stem cells; and articles with unavailable full text, we included 11 articles in our review. Results: The examined therapies encompassed mechanical micro-fragmented adipose tissue (MFAT) and stromal vascular fraction (SVF) obtained via collagenase digestion and centrifugation. These interventions were evaluated across various animal models, including mice, rats, rabbits, and sheep with induced OA. Notably, more studies concentrated on surgically induced OA rather than chemically induced OA. The assessment of these therapies focused on elucidating their protective immunomodulatory, anti-inflammatory, and chondroregenerative potential through comprehensive evaluations, including macroscopic assessments, histological analyses, immunohistochemical examinations, and biochemical assays. Conclusions: This review provides a comprehensive analysis of adipose tissue-derived injectable therapies for osteoarthritis across diverse animal models. While revealing potential benefits and insights, the heterogeneity of data and the limited number of studies highlight the need for further research to formulate conclusive recommendations for clinical applications.

Rationale for Using High-Frequency Ultrasound as a Routine Examination in Skin Cancer Surgery: A Practical Approach.

Ultrasound and high-frequency ultrasound assessment of melanoma and non-melanoma skin cancer in the pre-therapeutical setting is becoming increasingly popular in the field of dermatosurgery and dermatooncology, as it can provide clinicians with relevant, "in vivo" parameters regarding tumor lateral and depth extension as well as potential locoregional spread, cancelling the need of more extensive imaging methods and avoiding a delay in diagnosis. Furthermore, preoperative sonography and color Doppler can aid in orienting the clinical diagnosis, being able in numerous situations to differentiate between benign and malignant lesions, which require a different therapeutic approach. This preoperative knowledge is of paramount importance for planning an individualized treatment regimen. Using sonography at the time of diagnosis, important surgical complications, such as neurovascular damage, can be avoided by performing a preoperative neurovascular mapping. Furthermore, sonography can help reduce the number of surgical steps by identifying the lesions' extent prior to surgery, but it can also spare unnecessary surgical interventions in cases of locally advanced lesions, which infiltrate the bone or already present with locoregional metastases, which usually require modern radiooncological therapies in accordance to European guidelines. With this review, we intend to summarize the current indications of sonography in the field of skin cancer surgery, which can help us improve the therapeutic attitude toward our patients and enhance patient counseling. In the era of modern systemic radiooncological therapies, sonography can help better select patients who qualify for surgical procedures or require systemic treatments due to tumoral extension.

The utility of ultrasound for the diagnosis and treatment of primary and metastatic melanoma - a remaining oncological challenge.

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Pre-operative high-frequency ultrasound: a reliable management tool in auricular and nasal non-melanoma skin cancer.

BACKGROUND AND OBJECTIVES: The knowledge of depth infiltration in non-melanoma skin cancer (NMSC) using pre-operative ultrasound could enable clinicians to choose the most adequate therapeutic approach, avoiding unnecessary surgeries and expensive imaging methods, delaying diagnosis and treatment. Our single-center retrospective study determined the usefulness of high-frequency ultrasound (HFUS) for depth infiltration assessment in auricular and nasal NMSC and assessed the subsequent change in therapeutic approach. PATIENTS AND METHODS: In 60 NMSC cases, we assessed the accuracy of HFUS in cartilaginous/bone infiltration detection as well as the correlation of sonographic and histological parameters. RESULTS: In 16.6% of cases, a deep cartilaginous/bone involvement or locoregional disease was identified pre-operatively, resulting in a changed therapeutical scheme of radio-immunological treatment rather than surgery. In two cases, pre-operative HFUS identified local cartilage infiltration, reducing the number of surgical procedures. Forty-eight remaining lesions with no depth infiltration were excised; a correlation of > 99% between the histologic and sonographic tumor depth (p<0.001) was found. CONCLUSIONS: Pre-surgical HFUS influences the therapeutic management in NMSC by detecting subclinical involvement of deeper structures, avoiding more extensive diagnostics, reducing costs, and improving healthcare quality. High-frequency ultrasound should be implemented in dermatosurgery before tumor excision for optimized therapy and improved patient counseling.

Morphological aspects of basal cell carcinoma vascularization.

Basal cell carcinoma (BCC) is a malignant skin cancer which commonly exhibits aberrant blood flow because of angiogenesis. Its invasiveness and lack of metastatic potential may be explained by the typical pattern of vascularization seen in BCCs, where blood vessels are absent in the tumor islands and prominent in the tumor's periphery. From clinical point of view, high-frequency ultrasound (HFUS) is a useful tool for the evaluation of the lateral and depth extension of these tumors; furthermore, by employing color Doppler, important data regarding the vascularization degree of BCCs is provided. Knowingly, the sonographic vascular pattern of cutaneous tumors can aid in improving diagnosis and treatment by differentiating between benign and malignant lesions, between various types of cutaneous malignancies and also between various types of BCC (e.g., low risk versus high risk). Our aim was to perform a review integrating all currently known vascular properties of BCC as a tumor entity.

Ultrasonographic Assessment of Depth Infiltration in Melanoma and Non-melanoma Skin Cancer.

The preoperative assessment of infiltration depth in melanoma and non-melanoma skin cancer by means of high-frequency ultrasound (≥18 MhZ) is essential for optimizing the therapeutic approach in our patients. Often, histologically confirmed skin tumors are directly referred to surgical departments for resection, and sonography is increasingly helping us identify those subjects who are no longer candidates for extensive surgical interventions. In cases of deep tumor infiltration, with potential surgical failure e.g. impairment of the quality of life and significant esthetic and functional complications, preoperative sonography can guide the surgeon to withstand from an operation and decide instead in favor of less mutilating radiooncological or medical treatment options. Furthermore, in melanoma patients, the preoperative knowledge of the tumor depth is essential for the determination of the therapeutic approach, the correct safety margins and the need of a sentinelnode biopsy. We herein encourage the use of preoperative sonography in dermatologic surgery whenever possible as it represents an easy, painless, "in vivo" method, which provides clinicians with significant clinical information that can influence the therapy and improve patient compliance.

Ultrasonography in dermatologic surgery: revealing the unseen for improved surgical planning.

Ultrasonography (US) is a modern, in vivo imaging method, which is increasingly being used in dermatology as a complementary tool to clinical examination and dermoscopy. At higher frequencies (15 MHz and above), US is an established method for assessing benign and malignant skin lesions, locoregional staging, monitoring the therapeutic efficacy in various inflammatory skin conditions, and patient follow-up. One field, which may increasingly benefit from performant imaging techniques such as US is dermatologic surgery. Preoperative imaging of cutaneous tumors, inflammatory skin conditions (hidradenitis suppurativa, abscesses, etc.), or nail pathology provide dermatologic surgeons with relevant information for an optimal surgical planning, identifying potential complex aspects which might require interdisciplinary approaches, herein sparing unnecessary surgical interventions and increasing patients' compliance. In this review, we discuss the increasing significance of US in the field of dermatologic surgery, as well as the spectrum of cutaneous pathology where sonography can aid in the preoperative setting to provide a more precise, individualized surgical planning for better counseling to our patients and improved surgical results.

Techniques for digital histological morphometry of the pineal gland.

INTRODUCTION: The pineal gland is a small photo-neuro-endocrine organ. This study used human post-mortem pineal glands to microscopically assess immunohistochemical marker intensity and percentage of positivity using known and novel digital techniques. MATERIALS AND METHODS: An experimental non-inferiority study has been performed on 72 pineal glands harvested from post-mortem examinations. The glands have been stained with glial fibrillary acidic protein (GFAP), synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using optical analysis, CaseViewer, ImageJ, and MorphoRGB RESULTS: Strong and statistically significant correlations were found and plotted using Bland-Altman diagrams between the two image analysis software in the case of mean percentage and intensity of GFAP, NSE, NF, and SYN. DISCUSSIONS: Software such as SlideViewer and ImageJ, with our novel software MorphoRGB were used to perform histological morphometry of the pineal gland. Digital morphometry of a small organ such as the pineal gland is easy to do by using whole slide imaging (WSI) and digital image analysis software, with potential use in clinical settings. MorphoRGB provides slightly more accurate data than ImageJ and is more user-friendly regarding measurements of parenchyma percentage stained by immunohistochemistry. The results show that MorphoRGB is not inferior in functionality. CONCLUSIONS: The described morphometric techniques have potential value in current practice, experimental small animal models and human pineal glands, or other small endocrine organs that can be fully included in a whole slide image. The software we used has applications in quantifying immunohistochemical stains.

Assessment of Basal Cell Carcinoma Using Dermoscopy and High Frequency Ultrasound Examination.

Basal cell carcinoma (BCC) is the most common form of cutaneous neoplasia in humans, and dermoscopy may provide valuable information for histopathological classification of BCC, which allows for the choice of non-invasive topical or surgical therapy. Similarly, dermoscopy may allow for the identification of incipient forms of BCC that cannot be detected in clinical examination. The importance of early diagnosis using the dermoscopy of superficial BCC forms is proven by the fact that despite their indolent clinical appearance, they can be included in high-risk BCC forms due to the rate of postoperative recurrence. Nodular pigmentary forms of BCCs present ovoid gray-blue nests or multiple gray-blue dots/globules associated with arborized vessels, sometimes undetectable on clinical examination. The management of BCC depends on this, as pigmentary forms have been shown to have a poor response to photodynamic therapy. High frequency ultrasound examination (HFUS) aids in the diagnosis of BCC with hypoechoic tumour masses, as well as in estimating tumour size (thickness and diameter), presurgical margin delineation, and surgical planning. The examination is also useful for determining the invasion of adjacent structures and for studying local recurrences. The use of dermoscopy in combination with HFUS allows for optimisation of the management of the oncological patient.

Improved Water-Gas Shift Performance of Au/NiAl LDHs Nanostructured Catalysts via CeO2 Addition.

Supported gold on co-precipitated nanosized NiAl layered double hydroxides (LDHs) was studied as an effective catalyst for medium-temperature water-gas shift (WGS) reaction, an industrial catalytic process traditionally applied for the reduction in the amount of CO in the synthesis gas and production of pure hydrogen. The motivation of the present study was to improve the performance of the Au/NiAl catalyst via modification by CeO2. An innovative approach for the direct deposition of ceria (1, 3 or 5 wt.%) on NiAl-LDH, based on the precipitation of Ce3+ ions with 1M NaOH, was developed. The proposed method allows us to obtain the CeO2 phase and to preserve the NiAl layered structure by avoiding the calcination treatment. The synthesis of Au-containing samples was performed through the deposition-precipitation method. The as-prepared and WGS-tested samples were characterized by X-ray powder diffraction, N2-physisorption and X-ray photoelectron spectroscopy in order to clarify the effects of Au and CeO2 loading on the structure, phase composition, textural and electronic properties and activity of the catalysts. The reduction behavior of the studied samples was evaluated by temperature-programmed reduction. The WGS performance of Au/NiAl catalysts was significantly affected by the addition of CeO2. A favorable role of ceria was revealed by comparison of CO conversion degree at 220 °C reached by 3 wt.% CeO2-modified and ceria-free Au/NiAl samples (98.8 and 83.4%, respectively). It can be stated that tuning the properties of Au/NiAl LDH via CeO2 addition offers catalysts with possibilities for practical application owing to innovative synthesis and improved WGS performance.

Deep learning with transfer learning in pathology. Case study: classification of basal cell carcinoma.

Establishing basal cell carcinoma (BCC) subtype is sometimes challenging for pathologists. Deep-learning (DL) algorithms are an emerging approach in image classification due to their performance, accompanied by a new concept - transfer learning, which implies replacing the final layers of a trained network and retraining it for a new task, while keeping the weights from the imported layers. A DL convolution-based software, capable of classifying 10 subtypes of BCC, was designed. Transfer learning from three general-purpose image classification networks (AlexNet, GoogLeNet, and ResNet-18) was used. Three pathologists independently labeled 2249 patches. Ninety percent of data was used for training and 10% for testing on 100 independent training sequences. Each of the resulted networks independently labeled the whole dataset. Mean and standard deviation (SD) accuracy (ACC) [%]∕sensitivity (SN) [%]∕specificity (SP) [%]∕area under the curve (AUC) for all the networks was 82.53±2.63∕72.52±3.63∕97.94±0.3/0.99. The software was validated on another 50-image dataset, and its results are comparable with the result of three pathologists in terms of agreement. All networks had similar classification accuracies, which demonstrated that they reached a maximum classification rate on the dataset. The software shows promising results, and with further development can be successfully used on histological images, assisting pathologists' diagnosis and teaching.

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Position Statement on Dermatologic Ultrasound.

Dermatologic ultrasound is a recent application of ultrasound for the evaluation of healthy skin and appendages and their diseases. Although the scientific literature regarding this application is still not sufficient for evidence-based guidelines, general recommendations issued by scientific societies are necessary. The EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) steering committee for dermatologic ultrasound has developed a series of consensus position statements regarding the main fields of dermatologic ultrasound (technical requirement, normal skin and appendages, inflammatory skin diseases, tumoral skin diseases, aesthetic dermatology and practice-training requirements). This document is the foundation for future evidence-based recommendations and guidelines for dermatologic ultrasound practice.

High-frequency ultrasound: an essential non-invasive tool for the pre-therapeutic assessment of basal cell carcinoma.

AIM: While histology remains the "gold standard" for cutaneous tumoral pathology, high-frequency ultrasound (HFUS) was shown to play a significant role in the non-invasive, pre-therapeutic assessment of skin tumors. The aim of our study was to determine whether there is a significant correlation between the ultrasound (US) and histological measurements of basal cell carcinoma (BCC) tumor depth. MATERIALS AND METHODS: The present study retrospectively analyzed clinical, dermoscopy, HFUS and histological examinations of 90 patients (52 men and 38 women) with histologically confirmed BCC, with focus on tumor depth index (DI). RESULTS: On clinical examination, 54 lesions were nodular (32 presented ulcerations) and 36 superficial lesions. Dermoscopy showed suggestive signs of BCC, most frequently "in focus" arborising superficial vessels (n=81), blue-grey ovoid nests (n=48) and specks of brown pigment (n=7). HFUS revealed well-defined (n=88) or poorly defined (n=2) hypoechoic, vascularized lesions, with inhomogeneous structure (n=90) and characteristic hyperechoic dots (n=36). A strong correlation (Pearson's r=0.92) between the HFUS (mean measured US depth = 1.33 mm) and histological (mean measured histological depth = 1.47 mm) DI of the investigated skin lesions was found, although significant differences (p<0.001 - t-test for paired samples) between the two measurements were observed. CONCLUSIONS: HFUS provides reliable information about BCC depth of invasion that cannot be otherwise obtained prior to surgery. In this manner, it completes the preclinical evaluation and can have an impact on the choice of the optimal therapeutic method.

Use of imaging techniques for melanocytic naevi and basal cell carcinoma in integrative analysis (Review).

Early detection of skin cancer is essential in order to obtain an improved prognosis. Clinicians need more objective and non-invasive examination methods to support their decision whether to biopsy or not tumoral lesions. These may include several imaging techniques such as dermoscopy, videodermoscopy, also known as sequential digital dermoscopy (SDD), computer-aided diagnosis (CAD), total body photography, imaging and high-frequency ultrasonography (HFUS), reflectance confocal microscopy, multiphoton tomography, electrical impedance spectroscopy, Raman spectroscopy, stepwise two-photon-laser spectroscopy and quantitative dynamic infrared. This review summarizes the current developments in the field of melanocytic lesions, such as naevi and basal cell carcinoma (BCC) imaging techniques. The aim was to collect and analyze data concerning types, indications, advantages and disadvantages of modern imaging techniques for in vivo skin tumor diagnosis. Two main methods were focused on, namely videodermoscopy and HFUS, which can be included in daily dermatologists' practice. In skin tumors HFUS allows the assessment of tumoral lesions with depth smaller than 1.5 cm, being described a correlation between ultrasonographic depth and the histologic index.