Z-Plasty Made Simple

A Z-plasty is a critical and reliable technique that is useful for scar revisions and correction of free margin distortion. A Z-plasty can help lengthen a contracted scar, change the direction of a scar so that it is better aligned with the relaxed skin tension lines, or interrupt and break a scar for better camouflage. This article will review the technique of a basic Z-plasty as well as provide case examples of its use in free margin distortion and scar revision

Hemorrhagic complications in dermatologic surgery

exterior, detail of dome drum, 198

training.txt

<div>This is a training data set for our statistical analysis. The 2-D mass spectra files obtained by DESI-MS imaging were converted to delimited text files (.csv format) and exported for statistical analysis according to regions of interest of varying pathology using the MSIReader software.</div><div>We randomly divided the specimens into training set imaged at m/z 50–1200 (deposited here) and two sets of test specimens, one set imaged at m/z 150–1200, and the second one imaged at m/z 50–1200.</div><div><br></div

AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma.

Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal cell carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, but characteristics and drivers of the nMRTF cell state remain unknown. Here, we use single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlate with nMRTF and resistance to SMO inhibitors. The nMRTF cell state resembles transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation. JNK/AP-1 signaling commissions chromatin accessibility and Smad3 DNA binding leading to a transcriptional program of RhoGEFs that facilitate nMRTF activity. Importantly, small molecule AP-1 inhibitors selectively target LYPD3+/TACSTD2+/LY6D+ nMRTF human BCCs ex vivo, opening an avenue for improving combinatorial therapies

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment.

How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity-PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-β, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70's essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression

Systematic Review and Meta-Analysis of Local Recurrence Rates of Head and Neck Cutaneous Melanomas after Wide Local Excision, Mohs Micrographic Surgery, or Staged Excision

Background Prospective trials have not compared local recurrence rates for different excision techniques for cutaneous melanomas on the head and neck. Objective To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision. Methods A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies and randomized controlled trials that reported local recurrence rates after surgery of cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision. Results Among one-hundred manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE; 34.5% (4,826) by MMS; and 14.5% (2,034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95%CI, 0.1%-1.4%); followed by staged excision (1.8%; 95%CI, 0.1%-2.9%) and WLE (7.8%; 95%CI, 6.4%-9.3%). Limitations Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity. Conclusion Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE

Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas.

Hedgehog pathway-dependent cancers can escape Smoothened (SMO) inhibition through mutations in genes encoding canonical hedgehog pathway components; however, around 50% of drug-resistant basal cell carcinomas (BCCs) lack additional variants of these genes. Here we use multidimensional genomics analysis of human and mouse drug-resistant BCCs to identify a noncanonical hedgehog activation pathway driven by the transcription factor serum response factor (SRF). Active SRF along with its coactivator megakaryoblastic leukemia 1 (MKL1) binds DNA near hedgehog target genes and forms a previously unknown protein complex with the hedgehog transcription factor glioma-associated oncogene family zinc finger-1 (GLI1), causing amplification of GLI1 transcriptional activity. We show that cytoskeletal activation through Rho and the formin family member Diaphanous (mDia) is required for SRF-MKL-driven GLI1 activation and for tumor cell viability. Remarkably, nuclear MKL1 staining served as a biomarker in tumors from mice and human subjects to predict tumor responsiveness to MKL inhibitors, highlighting the therapeutic potential of targeting this pathway. Thus, our study illuminates, for the first time, cytoskeletal-activation-driven transcription as a personalized therapeutic target for combatting drug-resistant malignancies