Purpose
BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. Ultraviolet (UV) radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC.
Experimental Design
Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib (Vem) or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology.
Results
Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During Vem therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional-cSCC when controlled for gender and UV-exposure (p-value=0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK and EGFR mutations also detected.
Conclusions
We examined clinical, histopathologic, viral and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general.
A single treatment with a 585-nm pulsed dye laser appears to increase dermal collagen. This increase in dermal collagen can be assessed with noninvasive cutaneous ultrasound.
BACKGROUND. Cutaneous sutures should provide good wound eversion, firm closure, and cosmetically elegant results. Simple running sutures are commonly employed in cutaneous surgery but may not always be effective in achieving wound eversion. OBJECTIVE. We compared the cosmetic results of simple running nonabsorbable sutures with running horizontal mattress sutures in primary closures of facial defects. METHODS. Fifty-five patients with facial Mohs surgery defects appropriate for primary multilayer repair were randomized into one of two arms. Either the superior or the inferior half of the wound was closed with a running horizontal mattress suture. The other half of the wound was closed with a traditional simple running suture. At 1 week, 6 weeks, and 6 months, the cos-metically superior half of the wound, if any, was blindly determined by the investigators.RESULTS. The running horizontal mattress suture was significantly more cosmetically pleasing than the simple running suture. Forty-seven patients completed the study. At the 6-month followup, 25 patients did better with the horizontal suture and 5 did worse, and with 17 patients, there was no clinically perceptible difference. The 6-week scores predicted the outcome at 6 months, but the 1-week scores did not. CONCLUSIONS. In primary closures of the face, the running horizontal mattress suture is a cosmetically elegant alternative to a traditional running cutaneous suture. The final scar appears smoother and flatter than those produced by traditional simple running sutures.
These data indicate that the C-159T polymorphism of the CD14 gene is associated with TB; serum sCD14 levels were higher in TB patients in a sample of the Iranian population.
In primary closures of the face, the running horizontal mattress suture is a cosmetically elegant alternative to a traditional running cutaneous suture. The final scar appears smoother and flatter than those produced by traditional simple running sutures.
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