Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey.

By addressing the mechanisms involved in transcription, signaling, stress reaction, apoptosis and cell-death, cellular structure and cell-to-cell contacts, adhesion, migration as well as inflammation; HBO upregulates processes involved in repair while mechanisms perpetuating tissue damage are downregulated. Many experimental and clinical studies, respectively, cover wound healing, regeneration of neural tissue, of bone and cartilage, muscle, and cardiac tissue as well as intestinal barrier function. Following acute injury or in chronic healing problems HBO modulates proteins or molecules involved in inflammation, apoptosis, cell growth, neuro- and angiogenesis, scaffolding, perfusion, vascularization, and stem-cell mobilization, initiating repair by a variety of mechanisms, some of them based on the modulation of micro-RNAs. HBO affects the oxidative stress response via nuclear factor erythroid 2-related factor 2 (Nrf2) or c-Jun N-terminal peptide and downregulates inflammation by the modulation of high-mobility group protein B1 (HMGB-1), toll-like receptor 4 and 2 (TLR-4, TLR-2), nuclear factor kappa-B (NFκB), hypoxia-inducible factor (HIF-1α) and nitric oxide (NO•). HBO enhances stem-cell homeostasis via Wnt glycoproteins and mammalian target of rapamycin (mTOR) and improves cell repair, growth, and differentiation via the two latter but also by modulation of extracellular-signal regulated kinases (ERK) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. The HBO-induced downregulation of matrix metalloproteinases-2 and 9 (MMP-2/-9), rho-associated protein kinase (ROCK) and integrins improve healing by tissue remodeling. Interestingly, the action of HBO on single effector proteins or molecules may involve both up- or downregulation, respectively, depending on their initial level. This probably mirrors a generally stabilizing potential of HBO that tends to restore the physiological balance rather than enhancing or counteracting single mechanisms.

Excised melanocytic lesions in children and adolescents - a 10-year survey.

BACKGROUND: Early recognition and prompt excision is to date the only available strategy for reducing mortality from melanoma. Little is known about the accuracy of melanoma detection in children and adolescents. OBJECTIVES: To assess the accuracy of melanoma detection in a paediatric population. METHODS: From the Department of Dermatology, Medical University of Graz, Austria, we reviewed the dermatopathology reports of naevi and melanomas excised in patients younger than 20 years over a 10-year period (1998-2007). Patients were subdivided into four age groups: 0-4, 5-9, 10-14 and 15-19 years. RESULTS: Accuracy in melanoma detection was tested using the number needed to excise (NNE) value that is obtained by dividing the total number of excised lesions by the number of melanomas. A total of 22564 lesions were reviewed, disclosing 22526 naevi and 38 melanomas, for an overall NNE value of 593.8. Five melanomas were excised in children aged 10-14 years (NNE 1141) and 33 in children aged 15-19 years (NNE 479.8), whereas no melanomas were found among 1026 lesions excised in children younger than 10 years. In children aged 0-4 years, congenital and Spitz/Reed naevi accounted for 34.5% and 20% of lesions, respectively. These percentages decreased progressively when moving to older age groups (P<0.0001). In contrast, the percentage of dermal and compound naevi rose in direct proportion with age, being 3.4% and 20.7%, respectively, in the youngest age group, and 36.7% and 31.9%, respectively, among the oldest patients (P<0.0001). CONCLUSIONS: The overall NNE value in paediatric patients over the 10-year study period was 593.8, meaning that about 594 lesions were excised to find one melanoma. This value is 20 times higher than the rates found in adult patients.

In vivo reflectance confocal microscopy: automated diagnostic image analysis of melanocytic skin tumours.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) has been shown to be a valuable imaging tool in the diagnosis of melanocytic skin tumours. However, diagnostic image analysis performed by automated systems is to date quite rare. OBJECTIVES: In this study, we investigated the applicability of an automated image analysis system using a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in RCM. METHODS: Overall, 16,269 RCM tumour images were evaluated. Image analysis was based on features of the wavelet transform. A learning set of 6147 images was used to establish a classification tree algorithm and an independent test set of 10, 122 images was applied to validate the tree model (grouping method 1). Additionally, randomly generated 'new' learning and test sets, tumour images only and different skin layers were evaluated (grouping method 2, 3 and 4). RESULTS: The classification tree analysis correctly classified 93.60% of the melanoma and 90.40% of the nevi images of the learning set. When the classification tree was applied to the independent test set 46.71 ± 19.97% (range 7.81-83.87%) of the tumour images in benign melanocytic skin lesions were classified as 'malignant', in contrast to 55.68 ± 14.58% (range 30.65-83.59%; t-test: P < 0.036) in malignant melanocytic skin lesions (grouping method 1). Further investigations could not improve the results significantly (grouping method 2, 3 and 4). CONCLUSIONS: The automated RCM image analysis procedure holds promise for further investigations. However, to date our system cannot be applied to routine skin tumour screening.

Follow-up of actinic keratoses after shave biopsy by in-vivo reflectance confocal microscopy--a pilot study.

BACKGROUND: Monitoring of treatment efficacy after shave biopsy of actinic keratoses (AK) is often difficult, as clinical and dermoscopic features may not be reliable. OBJECTIVES: We investigated the applicability of in-vivo reflectance confocal microscopy (RCM) for the follow-up of AK after shave biopsy. METHODS: A total of 10 lesions were investigated by RCM before shave biopsy, after 3 and 12 months by two observers in agreement blinded to location, patients and time interval. RESULTS: At baseline all lesions showed typical clinical, dermoscopic and RCM criteria of AK. Three months after shave biopsy, all lesions presented clinically as normal skin (NS), but two lesions showed features suspicious for AK by RCM. After 12 months, one lesion of these two lesions changed into NS in RCM, whereas the other lesion progressed into clinical visible AK. At baseline, the two observers diagnosed 10 of 10 lesions correctly in RCM, after 3 months eight of 10 lesions and after 12 months all lesions were diagnosed correctly. CONCLUSIONS: Our results suggest that RCM might be a useful tool in the follow-up of AK after shave biopsy and might be used in inconclusive clinical and dermoscopic presentations of lesions after surgery or other treatment modalities.

Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study.

BACKGROUND: Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level. OBJECTIVES: To assess cytomorphological and architectural RCM features of facial LM/LMM. METHODS: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. The histopathological diagnosis of LM was made in 15 areas; the other two were diagnosed as early LMM. RESULTS: A focal increase of atypical melanocytes and nests surrounding adnexal openings, sheets of mainly dendritic melanocytes, cord-like rete ridges at the dermoepidermal junction (DEJ) and an infiltration of adnexal structures by atypical melanocytes were found to be characteristic RCM features of facial LM/LMM. Areas with a focal increase of atypical melanocytes and nests surrounding adnexal openings were observed at the basal layer in three cases. The remaining cases displayed these changes at suprabasal layers above sheets of mainly dendritic melanocytes. Cord-like rete ridges at the DEJ and an infiltration of adnexal structures by atypical melanocytes were observed in all cases. Previously described criteria for RCM diagnosis of melanoma, such as epidermal disarray, pleomorphism of melanocytes and pagetoid spreading of atypical melanocytes, were additionally observed. CONCLUSIONS: We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.

Confocal laser scanning microscopy-guided surgery for neurofibroma.

The neurofibromatoses comprise at least two separate genetic disorders with variable clinical features and an unpredictable course. The most common type, neurofibromatosis 1, is characterized by > or = 6 café-au-lait spots and the occurrence of neurofibromas, which may present as cutaneous, subcutaneous or plexiform lesions. Normally, excision of neurofibromas is only indicated in the presence of neurological symptoms, suspicion of malignancy or for exceptional cosmetic reasons. For a good functional and aesthetic result with the least danger of recurrence, the surgeon's goal is to excise as much tissue as necessary and as little tissue as possible. One of the main issues during the surgical procedure is to distinguish between neurofibroma and surrounding tissue. We report for the first time the use of confocal laser scanning microscopy to differentiate between neurofibroma and healthy skin.

In vivo confocal laser scanning microscopy in the diagnosis of melanocytic skin tumours.

Melanoma of the skin represents one of the greatest challenges in early or preventive detection. Whereas surgical excision in early stages of melanoma development is almost always curative, delayed recognition puts the patient at risk for destructive growth and death from disease once the tumour has progressed to competence for metastasis. The worldwide introduction of dermoscopy has led to improved diagnostic accuracy for melanocytic skin tumours. Whereas dermoscopy has probably reached the method's inherent potential diagnostic accuracy because of the lack of cellular level evaluation, further improvements could be expected by in vivo confocal laser scanning microscopy. In vivo confocal microscopy represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a 'quasihistopathological' resolution viewing microanatomical structures and individual cells. Numerous morphological confocal features of melanocytic skin tumours have been described and histopathological correlates of confocal structures have been previously elucidated. Recently, several studies have evaluated the diagnostic accuracy of in vivo confocal microscopy for melanocytic skin tumours, investigating approximately 50,000 tumour images. Remarkably, sensitivity superior to the diagnostic accuracy achieved with dermoscopy could be reached by this imaging modality. These studies represent a significant contribution to the body of research necessary for the evaluation and implementation of in vivo confocal microscopy in clinical practice to avoid many currently unnecessary biopsies. In vivo confocal microscopy probably augurs a sea change in the way we evaluate melanocytic skin tumours in the future and will ultimately move the art of histological diagnosis closer to the bedside.

In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images.

BACKGROUND: In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a 'quasi-histopathological' resolution viewing microanatomical structures and individual cells. OBJECTIVES: To validate diagnostic confocal examination of melanocytic skin tumours using unselected tumour images. METHODS: In the present study, we used a total of 3709 unselected CLSM tumour images obtained from 20 malignant melanomas and 50 benign naevi. The entire set of images derived from each tumour was evaluated by independent observers. Classification tree analysis based on a subsample of 857 tumour images was performed to develop a diagnostic algorithm. RESULTS: Overall, sensitivity and specificity of 97.5% and 99% could be achieved by the independent observers (positive predictive value 97.5%, negative predictive value 99%). Classification tree analysis yielded a three-step algorithm based on only three morphological CLSM features, facilitating a correct classification in 92.4% of the benign naevus images and 97.6% of melanoma images. CONCLUSIONS: In vivo CLSM augurs a sea change in the way we will view skin tumour processes clinically at the bedside and merits application for use as a screening tool in skin oncology.

Automatic identification of diagnostic significant regions in confocal laser scanning microscopy of melanocytic skin tumors.

OBJECTIVES: Confocal laser scanning microscopy (CLSM) is used for quick medical checkups. The aim of this study is to check the discrimination power of texture features for the automatic identification of diagnostic significant regions in CLSM views of skin lesions. METHODS: In tissue counter analysis (TCA) the images are dissected in equal square elements, where different classes of features are calculated out. Features defined in the spatial domain are based on histogram (grey level distribution) and co-occurrence matrix (grey level combinations). The features defined in the frequency domain are based on spectral properties of the wavelet Daubechie 4 transform (texture exploration at different scales) and the Fourier transform (global texture properties are localized in the spectrum). Hundred cases of benign common nevi and malignant melanoma were used as the study set. Classification was done with CART (Classification and Regression Trees) analysis which splits the set of square elements into homogenous terminal nodes and generates a set of splitting rules. RESULTS: Features based on the wavelet transform provide the best results with 96.0% of correctly classified elements from benign common nevi and 97.0% from malignant melanoma. The classification results are relocated to the images by use of the splitting rules as diagnostic aid. The discriminated square elements are highlighted in the images, showing tissue with features in good accordance with typical diagnostic CLSM features. CONCLUSION: Square elements with more than 80% of discrimination power enable the identification of diagnostic highly significant parts in confocal microscopic views of malignant melanoma.

Onychomycosis: a new emerging infectious disease in childhood population and adolescents. Report on treatment experience with terbinafine and itraconazole in 36 patients.

BACKGROUND: Onychomycosis is a rare disease in children with an estimated prevalence ranging from 0% to 2.6%. Thus far, only limited experience with itraconazole and terbinafine treatment in children with onychomycosis is available in the literature. AIM OF THE STUDY: Evaluation of treatment experience with itraconazole or terbinafine in childhood onychomycosis. SUBJECTS: Thirty-six children and adolescents (aged 4-17 years, 18 males and 18 females) with clinical and mycologically proven onychomycosis were enrolled in the present study. METHODS AND OUTCOME: In 27 of 36 patients, the causative agent (Trichophyton rubrum in 26 cases and Trichophyton interdigitale in one patient) could be identified by means of cultivation. Nineteen patients were treated with itraconazole 200 mg once daily for 12 weeks, and 17 patients were treated with terbinafine for 12 weeks in a dosage according to their body weight, respectively. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. CONCLUSION: To our experience, a mycological and clinical cure appears in children in a shorter time after treatment discontinuation (average 2-5 months) compared with adults. Itraconazole and terbinafine seem to be safe and effective in childhood onychomycosis; therefore, these antifungals seem to be potential alternatives to griseofulvin.