Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes.

Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC(-/-) background. XPC(-/-) cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk.

Frontal sinus repair through a frontalis rhytid approach.

Frontal sinus fractures have traditionally been repaired through a bicoronal approach. This incision provides a wide exposure, but is not without complications, particularly in the patient with or at risk for hairline recession. We present a series of 15 patients who underwent open reduction and internal fixation of anterior table frontal sinus fractures through a frontalis rhytid forehead incision and their results based on the scar appearance, forehead contour, frontalis function, sensation and fracture reduction. Paresthesias cranial to the incision in the supraorbital or supratrochlear distribution were noted in 12 of the 15 patients with resolution in all except 1 patient who did not regain sensation at 4 months follow-up. In all patients, satisfactory forehead contour and fracture reduction were achieved, as were scar appearance and frontalis function at 4 months follow-up. We thus recommend this approach in the treatment of anterior table frontal sinus fractures, with special consideration for the patient with or at risk for anterior hairline recession.

Single-stage forehead flap in nasal reconstruction.

The paramedian forehead flap has become the standard of care for major nasal reconstruction. The classic procedure involves a second-stage operation to divide and inset the external pedicle. We present our experience in a clinical series using single-stage forehead flap reconstruction. Our indications include elderly patients, pediatric patients treated during mission trips, and any patient in whom an external pedicle or two-stage procedure is problematic. From 2008 to 2009, 9 patients underwent a single-stage forehead flap. The majority had defects after excision of skin cancer. Our modification involves removal of radix and proximal nasal skin and fat and deepithelialization of the proximal pedicle to allow inset without excess compression or kinking. This modification avoids the sequelae of an external pedicle, which include bleeding, dressings, the inability to wear eyeglasses, and the patient's reluctance to appear in public. It safely provides acceptable results and avoids a mandatory secondary procedure.

Aesthetic reconstruction of severe postburn neck contractures.

Severe neck contractures after burns cause gross facial deformity and severe functional disability. Reconstruction of these deformities is challenging. Goals of reconstruction are to obtain full range of neck movements and to restore the aesthetic appearance to the face and neck. Several methods have been described. Although all of them focus on achieving full extension and resurfacing of the neck, they often fail to restore an aesthetic contour to the neck especially in lateral profile. We present our method based on the treatment of 96 patients, with severe neck contractures operated between September 2000 and October 2005. We have successfully achieved full unlimited range of neck movements and restored a natural pleasing contour of the neck both in anterior and lateral profile. There has been no recontracture at the follow-up of 1 year.