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.

Alterations of the Human Skin N- and O-Glycome in Basal Cell Carcinoma and Squamous Cell Carcinoma.

The glycome of one of the largest and most exposed human organs, the skin, as well as glycan changes associated with non-melanoma skin cancers have not been studied in detail to date. Skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are among the most frequent types of cancers with rising incidence rates in the aging population. We investigated the healthy human skin N- and O-glycome and its changes associated with BCC and SCC. Matched patient samples were obtained from frozen biopsy and formalin-fixed paraffin-embedded tissue samples for glycomics analyses using two complementary glycomics approaches: porous graphitized carbon nano-liquid chromatography electro spray ionization tandem mass spectrometry and capillary gel electrophoresis with laser induced fluorescence detection. The human skin N-glycome is dominated by complex type N-glycans that exhibit almost similar levels of α2-3 and α2-6 sialylation. Fucose is attached exclusively to the N-glycan core. Core 1 and core 2 type O-glycans carried up to three sialic acid residues. An increase of oligomannose type N-glycans and core 2 type O-glycans was observed in BCC and SCC, while α2-3 sialylation levels were decreased in SCC but not in BCC. Furthermore, glycopeptide analyses provided insights into the glycoprotein candidates possibly associated with the observed N-glycan changes, with glycoproteins associated with binding events being the most frequently identified class.

Role of high-resolution ultrasound and PET/CT imaging for preoperative characterization of sentinel lymph nodes in cutaneous melanoma.

The purpose of our study was the comparison of high-resolution ultrasound (HRUS) and positron emission tomography combined with computerised tomography (PET/CT) in the preoperative characterization and identification of subclinical nodal metastases focusing on sentinel lymph nodes (SLN) in melanoma patients. Patients with cutaneous melanoma (CM) who received sentinel lymph node biopsy at the Department of Dermatology and Allergy, University of Bonn, between January 2009 and January 2011 had been evaluated with a retrospective computer-aided search concerning preoperative staging procedures. A combination of PET/CT and HRUS had been performed preoperatively in 20 of 123 patients. A total of 59 SLNs had been removed in those 20 patients followed by histopathologic examination. HRUS correctly identified two of 17 positive SLNs whereas PET/CT imaging identified none. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HRUS were 11.8 % (95 % confidence interval [CI] = 3.3-34.3), 100 % (95 % CI = 91.6-100.0), 100.0 % (95 % CI = 34.2-100.0), and 73.7 % (95 % CI = 61.0-83.3), respectively. On the basis of this limited study cohort, HRUS had a better value than PET/CT in preoperative identification of positive SLNs, suggesting a possible diagnostic superiority of HRUS in general characterization of peripheral nodal disease in CM.

Preoperative characterization of basal cell carcinoma comparing tumour thickness measurement by optical coherence tomography, 20-MHz ultrasound and histopathology.

Optical coherence tomography (OCT) is a new imaging method with promising results for several dermatological indications, including preoperative skin tumour characterization. While high-frequency ultrasound (HFUS) is frequently used for this purpose, overestimation of tumour thickness is a problem, due to subtumoral inflammatory infiltration that cannot be differentiated from tumour tissue. The aim of this single-centre study was to describe OCT features of basal cell carcinoma (BCC) and to determine vertical tumour thickness accurately, including a comparison with HFUS and histopathology. Tumour thickness values of 10 BCCs measured by OCT did not differ significantly from those measured by histopathology (median difference 0.12 mm). By contrast, the difference between HFUS and histopathology was greater (median difference 0.3 mm). A Pearson's correlation coefficient of 0.83 showed a stronger correlation of OCT in measuring tumour thickness compared with HFUS (0.59). Bland-Altman plots revealed a better agreement of OCT and histopathology concerning tumour thickness measurements. On the basis of this explorative study cohort, OCt was more exact than HFUS in preoperative tumour thickness estimation of BCCs compared with histopathological measurements.

Assessment of tumor thickness in melanocytic skin lesions: comparison of optical coherence tomography, 20-MHz ultrasound and histopathology.

BACKGROUND: Accurate assessment of vertical tumor size is important for surgical treatment planning of melanocytic skin lesions. High-frequency ultrasound (HFUS) is frequently used for this purpose, but overestimation of tumor thickness is known as a problem especially in thin melanocytic lesions. Optical coherence tomography (OCT) as a new imaging technique might be a promising alternative. OBJECTIVE: To evaluate the ability of OCT to accurately determine the vertical tumor thickness of melanocytic skin lesions and to compare it with HFUS and histopathology in order to improve surgical planning. METHODS: In this single-center study, 26 melanocytic lesions were imaged by OCT and HFUS. Vertical lesion dimensions of both methods were compared with histopathological measurements. RESULTS: Bland-Altman plots for OCT and histopathology as well as for HFUS and histopathology revealed better agreement for OCT and histopathology concerning tumor thickness measurements. Tumor thickness values for the melanocytic lesions measured by OCT presented a median tumor thickness of 0.31 mm (range 0.10-0.77) compared to a median tumor thickness of 0.25 mm (range 0.06-1.5) measured by histopathology. The median tumor thickness of HFUS was 0.44 mm (range 0.23-1.1). A Spearman correlation procedure including the correlation coefficient (r) showed a stronger relationship between OCT and histopathology (r = 0.734) compared to HFUS and histopathology (r = 0.390). CONCLUSIONS: On the basis of this smaller study cohort, OCT seems to be more exact than HFUS as far as thickness determination of thin melanocytic skin lesions is concerned.

Efficacy of ablative laser treatment in Galli-Galli disease.

BACKGROUND: Galli-Galli disease (GGD) represents a rare genodermatosis that is clinically characterized by progressive reticulate hyperpigmentation of the flexures accompanied by itching and pain. To date, no convincing treatment options are known for GGD. We sought to examine the therapeutic potential of ablative laser treatment in a patient with genetically confirmed GGD. OBSERVATIONS: We describe a 68-year-old man with refractory bilateral axillary GGD accompanied by severe itching and pain. His clinical picture and histologic findings were consistent with GGD. Direct sequencing analysis of the KRT5 gene identified the causative mutation, c.418dupA, and confirmed the clinical diagnosis. The patient was treated with the erbium:YAG laser in 2 consecutive sessions for each side and was followed up for 12 months. Ablative laser treatment led to complete resolution of clinical symptoms and a good clinical result with only minimal scarring and dyspigmentation. CONCLUSIONS: This article demonstrates the efficacy of ablative laser treatment in a patient with genetically confirmed refractory GGD. However, further studies with longer follow-up are required to confirm these results.

Periocular milia en plaque successfully treated by erbium:YAG laser ablation.

Milia en plaque in the periocular region represent a cosmetically disturbing skin condition of unknown origin characterized by numerous tiny milia grouped around the inner canthus and the medial aspect of both eyelids. While conservative treatment and manual expression often result in local recurrence, invasive approaches harbor the risk of mechanical or thermal injury of periocular skin and lid margins. A 32-year-old female patient with refractory periocular milia was treated with the erbium:YAG laser and followed-up for 12 months. Ablative laser treatment led to nearly complete resolution of the milia and an excellent clinical result. Importantly, no scarring, dyspigmentation or ocular complications were noted. This report demonstrates the efficacy and safety of erbium:YAG laser ablation of periocular milia. The precise control of tissue ablation with minimal thermal damage makes the erbium:YAG laser an ideal tool for the treatment of the delicate periocular region where even minimal scarring can result in ocular complications.

Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma.

BACKGROUND: HAND2, a key regulator for the development of the sympathetic nervous system, is located on chromosome 4q33 in a head-to-head orientation with DEIN, a recently identified novel gene with stage specific expression in primary neuroblastoma (NB). Both genes are expressed in primary NB as well as most NB cell lines and are separated by a genomic sequence of 228 bp. The similar expression profile of both genes suggests a common transcriptional regulation mediated by a bidirectional promoter. RESULTS: Northern Blot analysis of DEIN and HAND2 in 20 primary NBs indicated concurrent expression levels of the two genes, which was confirmed by microarray analysis of 236 primary NBs (Pearson's correlation coefficient r = 0.65). While DEIN expression in the latter cohort was associated with stage 4S (p = 0.02), HAND2 expression was not associated with tumor stage. In contrast, both HAND2 and DEIN transcript levels were highly associated with age at diagnosis <12 months (p = 0.001). The intergenic region shows substantial homology in different species (89%, 72% and 53% identity between human and mouse, chicken and zebrafish, respectively) and contains many highly conserved putative transcription factor binding sites. Using luciferase reporter gene constructs, asymmetrical bidirectional promoter activity was found in four NB cell lines: In DEIN orientation, an average 3.4 fold increase in activity was observed as compared to the promoterless vector, whereas an average 15.4 fold activation was detected in HAND2 orientation. The presence of two highly conserved putative regulatory elements, one of which was shown to enhance HAND2 expression in branchial arches previously, displayed weak repressor activity for both genes. CONCLUSION: HAND2 and DEIN represent a gene pair that is tightly linked by a bidirectional promoter in an evolutionary highly conserved manner. Expression of both genes in NB is co-regulated by asymmetrical activity of this promoter and modulated by the activity of two cis-regulatory elements acting as weak repressors. The concurrent quantitative and tissue specific expression of HAND2 and DEIN suggests a functional link between both genes.

Identification of DEIN, a novel gene with high expression levels in stage IVS neuroblastoma.

Neuroblastoma at stage IVS, defined by dissemination to specific tissues and age <1 year at diagnosis, regularly follows spontaneous regression without cytotoxic treatment. To uncover the molecular characteristics of this subtype, Serial Analysis of Gene Expression (SAGE) profiles from stage IVS and fatal stage IV tumors were compared. A SAGE tag (GCAACTTAAC) was detected that was overrepresented in stage IVS disease and that had no reliable match in current National Center for Biotechnology Information databases of SAGE profiles, thus pointing to a novel gene. The corresponding gene, which maps to chromosome 4q33-34, was identified using a modified 3'- and 5'-rapid amplification of cDNA ends PCR and was designated as DEIN (differentially expressed in neuroblastoma). The gene comprises five transcript variants and its sequence overlaps with expressed sequences of the yet uncharacterized UniGene cluster Hs.61435. DEIN exhibits nucleotide sequence conservation over a broad range of species with an overall homology of 65% between human and mouse. As none of the predicted amino acid sequences is homologous to known proteins, it remains to be determined whether DEIN represents a coding or noncoding RNA. Northern blot analysis and semiquantitative reverse transcription-PCR showed high DEIN expression in neuroblastoma, whereas expression was absent or weak in most normal adult tissues. Analysis of 121 primary neuroblastomas by real-time reverse transcription-PCR revealed a strong association with age at diagnosis <1 year and particularly with stage IVS disease (both P < 0.001). The characteristic expression pattern of DEIN suggests a specific role of this gene in the unique biology of stage IVS tumors and may help to molecularly define this special subtype of neuroblastoma.