Summary
Heterogeneity of cancer-associated fibroblasts (CAFs) can result from activation of distinct signaling pathways. We show that in primary human dermal fibroblasts (HDFs), fibroblast growth factor (FGF) and transforming growth factor β (TGF-β) signaling oppositely modulate multiple CAF effector genes. Genetic abrogation or pharmacological inhibition of either pathway results in induction of genes responsive to the other, with the ETV1 transcription factor mediating the FGF effects. Duality of FGF/TGF-β signaling and differential ETV1 expression occur in multiple CAF strains and fibroblasts of desmoplastic versus non-desmoplastic skin squamous cell carcinomas (SCCs). Functionally, HDFs with opposite TGF-β versus FGF modulation converge on promoting cancer cell proliferation. However, HDFs with increased TGF-β signaling enhance invasive properties and epithelial-mesenchymal transition (EMT) of SCC cells, whereas HDFs with increased FGF signaling promote macrophage infiltration. The findings point to a duality of FGF versus TGF-β signaling in distinct CAF populations that promote cancer development through modulation of different processes.
The combination of TLA and dermatosurgery in infants is a suitable outpatient treatment option for small lesions without any major risks or side-effects and the benefit of prolonged postoperative analgesia.
The well-known negative psychological and social effects are a relevant part of HS and emphasize the importance of immediate therapy. As long-lasting local disease-control can be achieved, surgery should be considered as first-line therapy.
Summary
Tumescent local anesthesia (TLA) plays an important role in dermatosurgical procedures. TLA has several benefits such as long‐lasting anesthesia, reduced bleeding during surgery and the avoidance of general anesthesia‐associated complications. Convenience and a favorable risk profile along with a broad spectrum of indications are further reasons why TLA is increasingly applied in infants as well. There are not only a variety of indications for surgical excisions in infancy, such as congenital nevi, but also substantial benefits when performing these excisions at an early age. These include the smaller size of the lesions as well as the unproblematic wound healing and tissue regeneration in infancy. Nevertheless, several aspects need to be considered when applying TLA in infants including dosing, altered plasma protein binding and the need for adequate and long‐lasting pain control.
Background For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three-dimensional histology (3D-histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections.Objectives To investigate the rate of local recurrence (LR) as well as the number of required re-excisions for basal cell carcinomas with serial section histology vs. 3D-histology.Methods We compared serial sections histology with 3D-histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections.Results Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re-excisions were required in 21%; 24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D-histology group, re-excisions were required in 39%; 10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow-up was 4.5 years.Conclusions 3D-histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re-excisions. 3D-histology was associated with a significantly lower LR rate than serial section histology.
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