Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. AIM: To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. METHODS: In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. RESULTS: Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). CONCLUSION: LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.

Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.

BACKGROUND: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). METHODS: Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. RESULTS: Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. CONCLUSIONS: Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Dynamic optical coherence tomography shows characteristic alterations of blood vessels in malignant melanoma.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) allows in vivo visualization of blood vessels in the skin and in malignant tumours. Vessel patterns in malignant melanoma may be associated with tumour stage. OBJECTIVE: The aim of this study was to describe blood vessel patterns in melanomas and to correlate them with stage. METHODS: One hundred fifty-nine malignant melanomas were assessed in a multicentre study. Every tumour was imaged using D-OCT prior to surgery and histologic evaluation. The tumour data such as thickness and ulceration as well as the staging at primary diagnosis and a follow-up of at least 40 months resulted in a stage classification. The vessel patterns were assessed according to predefined categories, compared with healthy adjacent skin, and correlated to stage. RESULTS: Melanomas contained more blood vessels in different patterns compared with healthy adjacent skin. In particular, irregular vascular shapes such as blobs, coils, curves and serpiginous vessels were more common in melanomas. In addition, these patterns were significantly more often found in high-risk and metastatic melanomas than in low-risk lesions. CONCLUSION: In melanomas, the density of the blood vessels is increased, and irregular vascular patterns are more frequent. At higher stages, especially in metastatic melanomas, these atypical vessels are significantly more common.

[Noninvasive diagnostic imaging in pediatric skin lesions]. / Nichtinvasive bildgebende Diagnostik bei Hauterkrankungen im Kindesalter.

Optical coherence tomography (OCT) and reflectance confocal laser microscopy (RCM) allow noninvasive imaging diagnostics of the skin. Since the indication for a biopsy in children is generally made cautiously, OCT and KLM can be helpful in the clarification of pediatric skin lesions. In addition, biopsies only represent a snapshot of a small area of the skin, while noninvasive methods allow several locations to be examined over time, so that dynamic changes and the course of therapy can also be determined. In pediatric dermatology, these diagnostic methods are particularly suitable for the clarification of atypical pigment lesions, for infectious dermatoses such as scabies or tinea, and for the diagnosis of inflammatory and degenerative dermatoses.

Optical coherence tomography of basal cell carcinoma: influence of location, subtype, observer variability and image quality on diagnostic performance.

BACKGROUND: We previously described the principal results from an observational, prospective, multicentre, clinical trial of the diagnostic value of optical coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting. In this trial, much additional useful information was gathered that warranted further analysis, presented here. OBJECTIVES: To investigate the influence of candidate diagnostic criteria, OCT image quality, lesion location, and observer confidence and interobserver variability on the diagnostic performance of OCT, and to assess its potential use for diagnosis of BCC subtypes. METHODS: A total of 234 clinically unclear 'pink lesions' were evaluated in three steps: after clinical examination, after adding dermoscopy and after adding OCT. In addition to the diagnoses (including lesion subtype), observers recorded which of 15 diagnostic criteria the OCT image contained, their confidence in the diagnoses, the OCT image quality and the anatomical location of the lesion. RESULTS: Diagnostic performance of OCT did not depend on the lesion's anatomical location. Good OCT image quality was correlated with improved diagnostic performance, but diagnostic performance for lesions with mediocre image quality was still better than by clinical and dermoscopic examination. The main reason for reduced image quality was superficial scales and crusting. Observer confidence in diagnosis was correlated with diagnostic performance. Interobserver diagnostic performance was consistently higher than clinical examination and dermoscopy across all sites. BCC subtype could be determined with moderate accuracy, but further independent image markers are required. CONCLUSION: OCT is useful in the diagnosis of BCC.

Optical coherence tomography for margin definition of basal cell carcinoma before micrographic surgery-recommendations regarding the marking and scanning technique.

BACKGROUND/PURPOSE: Mohs Micrographic Surgery (MMS) is the preferred therapeutic treatment for high-risk basal cell carcinoma (BCC). Optical Coherence Tomography (OCT) is a non-invasive imaging technique that enables the diagnosis of BCC. We thought to determine the margins of BCCs with OCT, prior to MMS, to reduce the number of surgical steps. METHODS: Different permanent markers were tested on the skin regarding line width, resistance against disinfection and brightness in the OCT image. The visible tumor margins of BCCs were defined by dermoscopy, adding a safety margin of 2 mm and labeled using the selected pen, causing a signal shadow in OCT. Scans of the center and of entire margin were performed. If parts of the BCC were visible outside the margin, another 2 mm were added and the scan was repeated until the tissue outside the labeling looked tumor free. RESULTS: Eight out of ten BCCs were totally excised in a single stage when margin delineation was done by OCT. Macroscopic margins were enlarged after OCT scanning in four patients, saving further stages of MMS. CONCLUSION: OCT may help to better define the microscopic dimensions of BCCs and therefore reduce the number of stages of MMS.

Comparison of different optical coherence tomography devices for diagnosis of non-melanoma skin cancer.

PURPOSE: To compare the diagnostic imaging ability of three different optical coherence tomography (OCT) devices in non-melanoma skin cancer (NMSC). METHODS: Thirty actinic keratoses (AKs) and 27 basal cell carcinomas (BCCs) of 29 patients were examined with three different OCT devices, VivoSight® , Callisto® and Skintell® . RESULTS: Complete data sets were available for 16 BCCs and 10 AKs of 18 patients. All OCT devices were able to discriminate BCCs and AKs significantly from perilesional normal skin due to lower signal intensities as well as a thicker stratum corneum and epidermis in AKs. A significant decrease in the signal intensity and thickness of all skin layers was noted with Skintell® in contrast to VivoSight® and Callisto® . OCT comparisons revealed only slight differences between VivoSight® and Callisto® . Regarding BCC tumor thickness VivoSight® and Callisto® correlated well, histology did not correlate with the three OCT devices, whereas Skintell® showed no correlation with VivoSight® , Callisto® or histology. CONCLUSION: All tested OCT devices could identify BCCs and AKs objectively through standardized measurement of signal intensity and skin layer thickness. Due to their technical specifications (resolution, penetration depth), each of the OCT systems offers additional and special information on NMSC.

Optical coherence tomography of actinic keratoses and basal cell carcinomas - differentiation by quantification of signal intensity and layer thickness.

BACKGROUND: Previous studies have shown that actinic keratoses (AKs) and basal cell carcinomas (BCCs) can be diagnosed by optical coherence tomography (OCT) based on morphological characteristics. There is a lack of systematic studies that give standardized information on signal intensity and layer thickness of AKs and BCCs. OBJECTIVE: The aim of this study was to find out if AKs and BCCs can be objectively diagnosed through standardized measurement of signal intensity and layer thickness and to use OCT as a non-invasive objective method for the diagnosis and evaluation of AKs and BCCs. Additionally, tumour and skin layer thickness were investigated in correlation with histology. METHODS: In this experimental study, 301 lesions (188 BCCs and 113 AKs) of 125 patients were clinically as well as dermoscopically diagnosed and investigated with OCT before therapy. Normal perilesional skin served as control. RESULTS: It is possible to differentiate BCCs and AKs from normal skin in OCT due to the decrease of local signal intensity in affected skin layers in relation to adjacent healthy skin. In AKs, a strong thickness increase of the stratum corneum and epidermis compared to normal skin were observed. For the distinction between AKs and BCCs, a drop of signal intensity in the dermis of AKs towards BCCs and a thicker epidermis of AKs in contrast to BCCs were registered. All results are statistically highly significant (P < 0.0001). Besides, a strong correlation of tumour and skin layer thickness of BCCs and AKs in OCT with histology was found. CONCLUSION: Through standardized measurement of signal intensity and layer thickness, BCCs and AKs can be objectively diagnosed and distinguished from each other with OCT. This will further improve the use of OCT as a non-invasive objective method for the diagnosis and treatment monitoring of these diseases.

A giant planet orbiting the 'extreme horizontal branch' star V 391 Pegasi.

After the initial discoveries fifteen years ago, over 200 extrasolar planets have now been detected. Most of them orbit main-sequence stars similar to our Sun, although a few planets orbiting red giant stars have been recently found. When the hydrogen in their cores runs out, main-sequence stars undergo an expansion into red-giant stars. This expansion can modify the orbits of planets and can easily reach and engulf the inner planets. The same will happen to the planets of our Solar System in about five billion years and the fate of the Earth is matter of debate. Here we report the discovery of a planetary-mass body (Msini = 3.2M(Jupiter)) orbiting the star V 391 Pegasi at a distance of about 1.7 astronomical units (au), with a period of 3.2 years. This star is on the extreme horizontal branch of the Hertzsprung-Russell diagram, burning helium in its core and pulsating. The maximum radius of the red-giant precursor of V 391 Pegasi may have reached 0.7 au, while the orbital distance of the planet during the stellar main-sequence phase is estimated to be about 1 au. This detection of a planet orbiting a post-red-giant star demonstrates that planets with orbital distances of less than 2 au can survive the red-giant expansion of their parent stars.

[Digital and innovative teaching in dermatology : Practically oriented teaching online]. / Digitale und innovative Lehre in der Dermatologie : Praktisch orientierte Lehre online.

BACKGROUND: Due to the corona pandemic and also to the new competence-oriented catalogue of learning objectives in medicine and the master plan for medical studies 2020, the development of digital and practical teaching concepts has experienced a great increase in importance. AIM OF THE WORK: As a result of this development, it was an important task to establish this combination and incorporate it into the curricular teaching process. MATERIAL AND METHODS: The "Toolkit dermatology" was established, which was sent to a total of more than 650 students at German university dermatology clinics. Using educational films, the students were able to practice their skills. In a further development, the toolkit was combined with classroom lectures and the students were asked to evaluate the toolkit online. RESULTS: The vast majority of students (95-100%) clearly stated that the toolkit helped them to develop their practical skills. Some of them were in fact motivated to complete a clinical traineeship/practical tertial year in dermatology (21-88%). The combination of toolkit and subsequent classroom teaching was also rated very positively (82.2%), as this hybrid mode of teaching provided a better understanding. DISCUSSION: Digital teaching formats as part of the concept of blended learning, i.e. the combination of virtual and analogue teaching formats, are becoming increasingly more important. Solutions for the disadvantages, such as the lack of real interaction and suitable examination formats, still remain to be found; however, the toolkit project demonstrates that hands-on and digital teaching can lead to high student motivation as well as a high educational standard.

[Optical coherence tomography for skin pathologies]. / Optische Kohärenztomographie bei Pathologien der Haut.

Optical coherence tomography (OCT) has become established in routine diagnosis in dermatology only in the last few years. The reason is that the skin is a challenge for OCT as a strong scattering medium, because only a very small proportion of photons is reflected and can be used for imaging. In addition, in most cases a visual assessment or a biopsy is sufficient. Nevertheless, the main field of application in dermatology is the diagnostics of epithelial skin tumors. The OCT is suitable for the early recognition of small, clinically and light microscopically unspecific basal cell carcinomas as well as for the differential diagnosis of other tumors and precancerous lesions. Using OCT, the preoperative measurement of tumor spread, observation of the course and treatment control of non-surgical procedures are possible; therefore, in many cases a biopsy or treatment control can be avoided. Dynamic OCT is a newly developed add on technique to visualize and quantify the superficial blood vessels of the skin. First studies are focused on the evaluation of tumor vessels, wound healing and monitoring of laser therapy. In ophthalmology, OCT diagnostics of basal cell carcinomas on the eyelids as well as for planning and control of eyelid interventions can be of interest.

Investigation of factors that influence phosphorylation of pp60c-src on tyrosine 527.

Phosphorylation at tyrosine 527 of the proto-oncogene product, pp60c-src, has been proposed to decrease the tyrosine kinase activity of the enzyme. We have investigated potential factors that might influence phosphorylation at this site by making mutant variants of the pp60c-src protein. By effectively eliminating the site of N-terminal myristylation, we demonstrated that stable membrane association is not necessary for tyrosine 527 phosphorylation. Furthermore, mutational elimination of the enzymatic activity of this mutant pp60c-src protein did not alter the efficiency of phosphorylation at tyrosine 527. These data are consistent with the proposal that pp60c-src may be phosphorylated at tyrosine 527 by a cellular tyrosine kinase distinct from pp60c-src. In addition, using detergent-permeabilized cells, we established conditions that allow efficient phosphorylation of tyrosine 527 in vitro.

tpr-met oncogene product induces maturation-producing factor activation in Xenopus oocytes.

tpr-met, a tyrosine kinase oncogene, is the activated form of the met proto-oncogene that encodes the receptor for hepatocyte growth factor/scatter factor. The tpr-met product (p65tpr-met) was tested for its ability to induce meiotic maturation in Xenopus oocytes. While src and abl tyrosine kinase oncogene products have previously been shown to be inactive in this assay, p65tpr-met efficiently induced maturation-promoting factor (MPF) activation and germinal vesicle breakdown (GVBD) together with the associated increase in ribosomal S6 subunit phosphorylation. tpr-met-mediated MPF activation and GVBD was dependent on the endogenous c-mosxe, while the increase in S6 protein phosphorylation was not significantly affected by the loss of mos function. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine inhibits tpr-met-mediated GVBD at concentrations that prevent insulin- but not progesterone-induced oocyte maturation. Moreover, maturation triggered by tpr-met is also inhibited by cyclic AMP-dependent protein kinase. This is the first demonstration that a tyrosine kinase oncogene product, p65tpr-met, can induce meiotic maturation in Xenopus oocytes and activate MPF through a mos-dependent pathway, possibly the insulin or insulinlike growth factor 1 pathway.

Mutation of proline-1003 to glycine in the epidermal growth factor (EGF) receptor enhances responsiveness to EGF.

We have shown previously that the epidermal growth factor (EGF) receptor is phosphorylated at Ser-1002 and that this phosphorylation is associated with desensitization of the EGF receptor. Ser-1002 is followed immediately by Pro-1003, a residue that may promote the adoption of a specific conformation at this site or severe as a recognition element for the interaction of the EGF receptor with other proteins. To examine these possibilities, we have mutated Pro-1003 of the EGF receptor to a Gly residue and have analyzed the effect of this mutation on EGF-stimulated signaling. Cells expressing the P1003G EGF receptors exhibited higher EGF-stimulated autophosphorylation and synthetic peptide phosphorylation compared to cells expressing wild-type EGF receptors. In addition, the ability of EGF to stimulate PI 3-kinase activity and mitogen-activated protein kinase activity was enhanced in cells expressing the P1003G EGF receptor. Cells expressing P1003G receptors also demonstrated an increased ability to form colonies in soft agar in response to EGF. These results indicate that mutation of Pro-1003 leads to a potentiation of the biological effects of EGF. The findings are consistent with the hypothesis that Pro-1003 plays a role in a form of regulation that normally suppresses EGF receptor function.

Clinical-physiologic correlations in acute asthma of childhood.

Seventy-one patients who presented to the emergency room with acute asthma were evaluated to determine the relationship between common clinical signs and spirometric and transcutaneous arterial oxygen saturation (SaO2) measurements. Prior to treatment, a physical examination was performed, a clinical score assigned, and pulmonary function and SaO2 were measured. Although forced expiratory volume in 1 second (FEV1) and SaO2 had strong correlation with the overall clinical score (r2 = .47, .49 respectively), many patients with low clinical scores and apparent mild clinical disease had low FEV1 values (as low as 20% predicted). Of the individual components of the clinical score (ie, heart rate, respiratory rate, pulsus paradoxus, accessory muscle use, dyspnea, and wheezing), the degree of accessory muscle use correlated most closely with lung function followed by the degree of dyspnea and wheezing. Similarly, the degree of accessory muscle use correlated most closely with SaO2 followed by dyspnea and respiratory rate. Significant correlation (r2 = .59) was found between SaO2 and FEV1, although the range of SaO2 value for a given FEV1 was wide and some patients with low FEV1 values had normal SaO2 values. These results show that although clinically apparent severe disease and hypoxemia were always associated with low FEV1, their absence does not exclude the presence of airflow obstruction. It is concluded that for the optimal evaluation of acute asthma in children in the emergency room, clinical evaluation should be used in conjunction with objective laboratory measurements.

High-versus low-dose, frequently administered, nebulized albuterol in children with severe, acute asthma.

Thirty-two 5- to 17-year-old children who had severe, acute asthma were randomly assigned to receive either high doses (0.15 mg/kg of body weight per dose) or low doses (0.05 mg/kg of body weight per dose) of nebulized albuterol every 20 minutes for six doses. Compared with the low-dose regimen, the high-dose regimen resulted in significantly greater improvement in forced expiratory volume in 1 second, forced vital capacity, and wheeze score and a lower hospitalization rate. The changes in heart rate, respiratory rate, blood pressure, white blood cell count, and serum potassium concentration did not differ significantly between the groups. The incidence of side effects, which included tremor, hyperactivity, and vomiting, was not significantly different in the two populations. Serum albuterol levels varied widely, but there was no correlation between the levels and the increase in heart rate or other side effects. high-dose, frequently administered, nebulized albuterol appears both safe and effective in treating severe, acute asthma in children.

Nebulized albuterol in acute childhood asthma: comparison of two doses.

Thirty-three children and adolescents from 5 to 17 years of age with moderate to severe acute asthma were given nebulized albuterol therapy in either a high (0.30 mg/kg body weight) or standard (0.15 mg/kg) dose administered at three hourly intervals in a randomized double-blind study. The high-dose hourly regimen resulted in significantly greater improvement in the forced expiratory volume in 1 second (FEV1). Furthermore, patients receiving the high dose showed a steady improvement in the FEV1 from the start to the end of the study, whereas FEV1 plateaued after the second dose in the standard-dose group. Although a rise in heart rate and a fall in serum potassium level occurred, neither of these changes nor other side effects were different in the two groups. The high-dose therapy resulted in much higher serum albuterol levels than the standard dose. There was no correlation between the drug levels and side effects or initial and subsequent FEV1. It is concluded that occasional hourly high-dose albuterol therapy should be considered for some pediatric patients with acute asthma of moderate severity, especially those who relapse between doses.

Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma.

To determine the response to nebulized beta 2 agonist, 28 children younger than 2 years of age who visited the emergency department during an episode of acute asthma were studied. Each subject had a previous history of recurrent wheezing episodes. They were randomly assigned to receive two administrations of either nebulized albuterol (0.15 mg/kg per dose) or placebo (normal saline) with oxygen, 1 hour apart. After two nebulizations, the albuterol-treated patients had a greater improvement in clinical status (respiratory rate, degree of wheezing and accessory muscle use, total clinical score, and arterial oxygen saturation) than the placebo group. None of the patients in the albuterol group experienced a decrease of arterial oxygen saturation of greater than or equal to 2%. It is concluded that a trial of nebulized beta 2 agonists is warranted in the treatment of acute asthma in infants and young children.