Diagnosis of Basal Cell Carcinoma with Ex-vivo Confocal Laser Scanning Microscopy in a Real-life Setting.

Ex-vivo confocal laser scanning microscopy provides a rapid alternative to routine histological processing using haematoxylin and eosin-stained sections. Previous studies suggest high diagnostic accuracy in basal cell carcinoma. This study investigates the diagnostic accuracy of confocal laser scanning microscopy reporting of basal cell carcinoma in a real-life setting and compares reporting by dermatopathologists inexperienced in use of confocal laser scanning microscopy with reporting by an expert in confocal laser scanning microscopy. A total of 334 confocal laser scanning microscopy scans were diagnosed by 2 dermatopathologists inexperienced in the diagnosis of confocal laser scanning microscopy as well as an experienced examiner of confocal laser scanning microscopy scans. The inexperienced examiners achieved a sensitivity of 59.5/71.1% and specificity of 94.8/89.8%. The experienced examiner achieved a sensitivity of 78.5% and specificity of 84.8%. Detection of tumour remnants in margin controls showed insufficient values among inexperienced (30.1/33.3%) and experienced (41.7%) investigators. The results of this study, of real-life setting basal cell carcinoma reporting with confocal laser scanning microscopy, found a lower diagnostic accuracy than published data regarding artificial settings. A poor accuracy in tumour margin control is clinically relevant and could restrict the use of confocal laser scanning microscopy in clinical routine. Prior knowledge of haematoxylin and eosin trained pathologists can be partially transferred to the reporting of confocal laser scanning microscopy scans; however, specific training is recommended.

Metabolomics of Human Semen: A Review of Different Analytical Methods to Unravel Biomarkers for Male Fertility Disorders.

BACKGROUND: Human life without sperm is not possible. Therefore, it is alarming that the fertilizing ability of human spermatozoa is continuously decreasing. The reasons for that are widely unknown, but there is hope that metabolomics-based investigations may be able to contribute to overcoming this problem. This review summarizes the attempts made so far. METHODS: We will discuss liquid chromatography-mass spectrometry (LC-MS), gas chromatography (GC), infrared (IR) and Raman as well as nuclear magnetic resonance (NMR) spectroscopy. Almost all available studies apply one of these methods. RESULTS: Depending on the methodology used, different compounds can be detected, which is (in combination with sophisticated methods of bioinformatics) helpful to estimate the state of the sperm. Often, but not in all cases, there is a correlation with clinical parameters such as the sperm mobility. CONCLUSIONS: LC-MS detects the highest number of metabolites and can be considered as the method of choice. Unfortunately, the reproducibility of some studies is poor, and, thus, further improvements of the study designs are needed to overcome this problem. Additionally, a stronger focus on the biochemical consequences of the altered metabolite concentrations is also required.

Covering of large scalp defects prior to postoperative irradiation.

BACKGROUND AND OBJECTIVE: After R0 resection of extensive cutaneous squamous cell carcinoma of the scalp with indication for postoperative radiotherapy, closure techniques should be chosen that allow rapid initiation of radiotherapy. The aim of this retrospective analysis is to evaluate defect coverage by transverse transposition flap and split skin grafting of the donor site in such a scenario with regard to oncologic safety (recurrence rate) and permanence of wound closure. PATIENTS AND METHODS: Eleven patients were identified who had histologic cutaneous squamous cell carcinoma treated by microscopically controlled excision and defect coverage using a transverse transposition flap and split skin grafting of the donor site and who received postoperative radiotherapy. Patients were evaluated for recurrence, wound healing disorders and side effects of radiotherapy. RESULTS: The mean age was 81 years. Follow-up time averaged 1.4 years after the last radiotherapy session. Wound healing disorders of the transposition flap or graft necrosis were not detected. All therapy-associated side effects had resolved at follow-up. Local recurrence or metastasis did not occur. CONCLUSIONS: Combined transverse transposition flap plasty with split-skin grafting of the donor site is a safe treatment concept with few side effects for large scalp defects with exposed calvaria requiring postoperative radiotherapy.

S2k guideline: Laser therapy of the skin.

This guideline aims to improve the efficiency and safety of lasers and optical radiation sources with similar effects (especially IPL). Laser therapy of skin lesions with an increased amount of melanocytes should be performed with caution. Laser treatment of pigmented melanocytic nevi is not recommended. The guideline contains recommendations regarding the treatment of lentigines and café-au-lait spots, non-pigmented dermal nevi, Becker nevus, nevus of Ota/Hori/Ito and melasma. Further recommendations focus on the treatment of skin lesions without an increased amount of melanocytes (ephelides, postinflammatory hyperpigmentation including berloque dermatitis, seborrheic keratoses, traumatic/decorative tattoos and metallic deposits), hypopigmentation (vitiligo), benign non-pigmented neoplasms (fibrous papule of the nose, nevus sebaceus, epidermal nevus, neurofibroma, sebaceous gland hyperplasia, syringoma, xanthelasma palpebrarum), inflammatory dermatoses (acne papulopustulosa/conglobata, acne inversa, granuloma faciale, lichen sclerosus, lupus erythematosus, psoriasis vulgaris, rosacea, rhinophyma), wrinkles/dermatochalasis/striae, hypertrichosis, scars (atrophic, hypertrophic; keloids, burn/scald scars), laser-assisted skin healing, onychomycosis, precancerous lesions and malignant tumors (actinic keratoses/field cancerization, cheilitis actinica, basal cell carcinoma), vascular skin lesions (angiokeratoma, angioma, hemangioma, malformation, spider veins, granuloma telangiectaticum (pyogenic granuloma), rubeosis (erythrosis interfollicularis colli, ulerythema ophryogenes), nevus flammeus, telangiectasias and Osler's disease (hereditary hemorrhagic telangiectasia) and viral skin lesions (condylomata acuminata, mollusca contagiosa, verrucae planae juveniles/vulgares/ verrucae palmares et plantares).

Differences in the sperm metabolomes of smoking and nonsmoking men†.

Currently, spermiogram analysis is the most relevant method used to clarify the potential infertility of a couple. However, in some cases, the reasons for infertility remain obscure. Smoking is among the factors that have been described to adversely affect male fertility. Smoking increases oxidative stress and thus promotes various pathological processes. Comparative studies, particularly those on metabolomic changes in sperm and seminal plasma caused by smoking, have not yet been published. Thus, the present pilot study aimed at the mass spectrometric characterization of the metabolomes of specimens from both smoking and nonsmoking subjects and the comparison of the evaluated data in terms of sperm apoptosis and spermiogram parameters. The results provided evidence that the conventional spermiogram is not altered in smokers compared to nonsmokers. However, a more careful investigation of sperm cells by metabolomic profiling reveals profound effects of smoking on sperm: first, nitrogen oxide synthase, a marker of oxidative stress, is activated. Second, the uptake of fatty acids into sperm mitochondria is reduced, leading to an impaired energy supply. Third, phenylalanine hydroxylation and tryptophan degradation, which are both indications of altered tetrahydrobiopterin biosynthesis, are reduced. Moreover, flow cytometry approaches indicated increased sperm caspase-3 activity, a sign of apoptosis. The present study clearly shows the negative effects of smoking on semen quality. Especially for idiopathic cases, metabolomic profiling can help to shed light on male subfertility or infertility.

Reduced lipolysis in lipoma phenocopies lipid accumulation in obesity.

BACKGROUND: Elucidation of lipid metabolism and accumulation mechanisms is of paramount importance to understanding obesity and unveiling therapeutic targets. In vitro cell models have been extensively used for these purposes, yet, they do not entirely reflect the in vivo setup. Conventional lipomas, characterized by the presence of mature adipocytes and increased adipogenesis, could overcome the drawbacks of cell cultures. Also, they have the unique advantage of easily accessible matched controls in the form of subcutaneous adipose tissue (SAT) from the same individual. We aimed to determine whether lipomas are a good model to understand lipid accumulation. METHODS: We histologically compared lipomas and control SAT, followed by assessment of the lipidome using high-resolution 1H NMR spectroscopy and ESI-IT mass spectrometry. RNA-sequencing was used to obtain the transcriptome of lipomas and the matched SAT. RESULTS: We found a significant increase of small-size (maximal axis < 70 µm) and very big (maximal axis > 150 µm) adipocytes within lipomas. This suggests both enhanced adipocyte proliferation and increased lipid accumulation. We further show that there is no significant change in the lipid composition compared to matched SAT. To better delineate the pathophysiology of lipid accumulation, we considered two groups with different genetic backgrounds: (1) lipomas with HMGA2 fusions and (2) without gene fusions. To reduce the search space for genes that are relevant for lipid pathophysiology, we focused on the overlapping differentially expressed (DE) genes between the two groups. Gene Ontology analysis revealed that DE genes are enriched in pathways related to lipid accumulation. CONCLUSIONS: We show that the common shared lipid accumulation mechanism in lipoma is a reduction in lipolysis, with most gene dysregulations leading to a reduced cAMP in the adipocyte. Superficial lipomas could thus be used as a model for lipid accumulation through altered lipolysis as found in obese patients.

Routine application of ex vivo confocal laser scanning microscopy with digital staining for examination of surgical margins in basal cell carcinomas.

BACKGROUND AND OBJECTIVES: Ex vivo confocal laser scanning microscopy (CLSM) allows histologic examination of native tissue based on tissue reflection and nuclear fluorescence staining. The newly introduced digital staining process almost perfectly mimics conventional hematoxylin and eosin (HE) slides. The aim was to evaluate the new method in clinical routine, with regard to quality of findings and time requirements, in the examination of surgical margins of basal cell carcinomas. PATIENTS AND METHODS: 78 patients with 101 basal cell carcinomas were prospectively enrolled. Surgery was performed either with complete margin control (n = 60) or as elliptical excision (n = 41). Immediately after excision specimens were scanned with CLSM and then routinely processed by conventional histopathology. Blinded evaluation of images and slides was performed by a dermatopathologist. RESULTS: Basal cell carcinomas were excellently recognizable by CLSM directly after excision, and the use of digital staining did not require any adjustment of the examiner's visualization preferences. CLSM images showed a sensitivity of 73.6 % and a specificity of 96.5 % compared to conventional HE stained slides. Erroneous findings were often due to limited assessment potential in cases where the epidermis could not be fully visualized. CONCLUSIONS: CLSM with digital HE staining is very well suited to diagnose basal cell carcinomas and their incision margins even under routine conditions and thus represents a tissue-saving alternative to rapid cryostat sectioning.

Update on dermatologic laser therapy II - advances in photodynamic therapy using laser-assisted drug delivery.

Technical advances in recent years have led to the development of new dermatologic laser systems, light sources, and treatment concepts. With the introduction of ablative fractional lasers (using common wavelengths) in the field of dermatology, it is now possible to more effectively and efficiently treat a variety of skin disorders. One important example of these advances is laser-assisted drug delivery (LADD). A type of LADD, laser-assisted photodynamic therapy has been successfully employed in the treatment of non-melanoma skin cancer including field cancerization. This treatment concept has been continually modified and today includes the use of daylight as well as artificial daylight systems. This update is based as cited, shortened and updated according to "Paasch,U. 2019. Laser-assistierte photodynamische Therapie. p. 226-239. In G.Kautz (ed.) Energie für die Haut. Springer Nature, Springer Nature".

Update Dermatologische Lasertherapie II - Weiterentwicklung der photodynamischen Therapie durch Laser-assistierte transkutane Applikation von Topika.

Die technische Fortentwicklung der jüngeren Vergangenheit bietet dem Dermatologen Zugriff auf neue Laser, Strahlquellen und Behandlungskonzepte. Seit langem eingeführte Wellenlängen zur Ablation sind nunmehr fraktioniert applizierend verfügbar und stehen nunmehr für eine wirksamere und effizientere Behandlung von zahlreichen Hautveränderungen zur Verfügung. Das gezielte Einbringung von Topika (laser assisted drug delivery; LADD) ist das wichtigste Beispiel. Die LADD erfordert eine spezifische Weiterbildung, um sicher und wirksam zur Therapie (prä-)maligner nichtmelanozytärer Neoplasien der Haut wie der Feldkanzerisierung in Form der Laser-assistierten photodynamischen Therapie angewandt werden zu können. Bisher verfügbare Daten weisen auf eine höhere Effektivität im Vergleich zu konventionell verwendeten Topika hin, wobei anhaltend über Weiterentwicklungen berichtet wird. Unter anderem wurde die Kombination mit Tageslicht oder alternativen tageslichtähnlichen Strahlquellen bekannt. Dieses Update basiert wie zitiert gekürzt und aktualisiert auf "Paasch, U. 2019. Laser-assistierte photodynamische Therapie. p. 226-239. In G. Kautz (ed.) Energie für die Haut. Springer Nature, Springer Nature.".

Full ablative versus fractional ablative laser therapy for Dowling-Degos disease.

Dowling-Degos disease (DDD) is a rare autosomal-dominant genodermatosis with limited treatment possibilities. Although the efficacy of ablative laser therapy has been reported, we sought to examine the efficacy of fractional versus full ablative laser therapy in a female patient with DDD in a split-side report. We treated the lesions on the right side of the patient's upper abdomen with an ablative fractional CO2 laser and the lesions on the left side of the upper abdomen with a full ablative Er:YAG laser (erbium-doped yttrium aluminium garnet laser) three times at monthly intervals. After three laser sessions, the lesions treated with the Er:YAG laser showed a complete response, whereas the fractional CO2 laser treatment was less effective. After the three treatments were performed, the right side of the patient's upper abdomen and portions of her lower abdomen and chest were also treated with the Er:YAG laser in full ablation mode with the same settings. After 1 year of follow up, there was no recurrence observed. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Automated semen analysis by SQA Vision® versus the manual approach-A prospective double-blind study.

Next to clinical investigations, the evaluation of male fertility relies mainly on detailed sperm analyses, for example, cell counting, motility, cell morphology and vitality testing. The manual creation of a spermiogram is time- and material-consuming. Therefore, reliable high-throughput systems that may be substituted for manual methods are urgently needed. The present study aimed to compare conventional sperm analysis performed as per WHO 5th guidelines and semen analysis performed with the SQA Vision® machine. SQA Vision® is a commercial device for automated sperm analysis. Data obtained independently by both methods were compared by statistical analyses using Bland-Altman plots and Passing-Bablok regression analyses. The analyses revealed that the results for sperm concentration and total motility were comparable. The agreement for progressive motility was poor, and there were clear deviations in the determination of normal sperm morphology. Passing-Bablok regression analyses and the consideration of the 95% confidence intervals pointed out systematic and proportional differences between the manual semen analysis and the automated approach.

[Rare form of a segmental neurofibromatosis with giant plexiform neurofibroma]. / Seltene Form einer segmentalen Neurofibromatose mit monströsem plexiformem Neurofibrom.

The case of segmental neurofibromatosis (NF) with a monstrous plexiform neurofibroma in a 53-year-old female patient is described. Segmental NF is a rare form of NF, which is caused by a postzygotic mutation in the NF1 gene. In this mosaic form the typical cutaneous symptoms of NF are limited to certain unilateral dermatomes. Plexiform neurofibromas are clinically and histologically in contrast to locally delimited neurofibromas. They involve the catchment area of a peripheral nerve, affect many fascicles and nerve branches, do not respect growth limits and spread in a reticulated fashion. Plexiform neurofibromas can become malignant. In the presented case large parts of the monstrous plexiform cutaneous neurofibroma were excised and the patient did not wish any further measures to be carried out for the time being.

[Dermatological follow-up in retinoblastoma patients : A case report]. / Dermatologische Tumornachsorge bei Retinoblastompatienten : Ein Fallbericht.

We report a well-differentiated liposarcoma and multiple lipomas in a patient with bilateral retinoblastoma at the age of two. Well-differentiated liposarcoma of the skin are rare and have a good prognosis. Lipomas are in those cases a good indicator for a higher risk of secondary cancer. There is no standardized aftercare program. We recommend therefore regular clinical-dermatological examinations every 6 months and if necessary an early excision of suspicious lesions.

[Andrological consultation in new systemic oncological therapies with small molecules]. / Andrologische Beratung bei neuen onkologischen Systemtherapien mit "small molecules".

Small molecules are rapidly broadening the spectrum of systemic oncologic therapies. Targets of those drugs are-among others-tyrosine and serine/threonine kinases like VEGF-R, EGF-R, Bcr-Abl, c­kit, JAK, CDK as well as BRAF and MEK. Clinical data of potential risks to male fertility are still very limited and are generally only available for older preparations. In addition, they are often multikinase inhibitors, so that even small molecules with the same (main) target are not completely comparable. For fertility protection, sperm cryopreservation should be offered to men seeking fatherhood before starting targeted therapy.

2018 update on dermatologic laser therapy: Part 1 - epilation, vascular lesions and pigments.

Technical advances in recent years have led to new dermatologic laser systems, light sources, and treatment concepts. Commonly used wavelengths - generated today with LED-based devices - allow for the combination of various tissue effects and are associated with improved outcomes. Laser hair removal has become more efficient with the use of diode lasers that emit multiple wavelengths simultaneously. In the near future, novel LED-based lasers will also be introduced for the treatment of vascular lesions. Here, too, the combination of different wavelengths promises to be beneficial. Picosecond lasers have led to advances in the field of pigment removal (tattoos).

Neue Laser und Strahlquellen - alte und neue Risiken?

Die Entwicklungen im Bereich dermatologischer Laser, hochenergetischer Blitzlampen, LED und neuer Energie- und Strahlquellen der letzten Jahre haben gezeigt, dass mit neuen Wellenlängen, Konzepten und Kombinationen zusätzliche, zum Teil über den ästhetischen Bereich hinaus gehende therapeutische Optionen für den Dermatologen erschlossen werden konnten. Wurden bisher zum Beispiel mit fraktionalen Lasern Falten behandelt, sind eben diese Systeme heute in Kombination mit Medikamenten wichtige Werkzeuge bei der Behandlung von Narben, bei Feldkanzerisierung und epithelialen Tumoren. Die Anforderungen an den die Indikation stellenden und vorzugsweise therapierenden Arzt steigen mit der immer komplexer werdenden Technik und den zunehmenden Komorbiditäten und Komedikationen einer älter werdenden Patientenklientel. Parallel etabliert wurden, zunächst für einige wenige Indikationen, Geräte für die Heimanwendung, die sich durch geringe Leistung und spezielle Sicherheitsvorkehrungen zur Vermeidung von Unfällen, Risiken und Nebenwirkungen auszeichnen. Trotz der reduzierten Effizienz solcher Selbstbehandlungsmaßnahmen steigt die Wahrscheinlichkeit einer Fehlanwendung, da die Grundvoraussetzung für eine korrekte Therapie, nämlich die exakte Diagnose und Indikationsstellung, nicht vorausgesetzt werden kann. Bei einer Haarentfernung können so Pigmenttumoren, bei einer Faltentherapie neoplastische Hautveränderungen adressiert und zu erwartende, unvorhergesehene und neue Nebenwirkungen und Komplikationen induziert werden. In diesem Szenario ist es wichtig, alle potenziellen Anwender dieser neuen Technologien vor deren Einsatz so zu qualifizieren, dass den Therapierten maximale Therapiesicherheit bei höchster Effizienz unter dem Leitbild diagnosis certa - ullae therapiae fundamentum garantiert wird.