https://www.thelancet.com/pdfs/journals/lancet/PIIS014067360961196X.pdf

Non-melanoma skin cancer

Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis.

/pdf/oxidative-stress-in-aging-human-skin-3ohc7c9zri.pdf

Oxidative Stress in Aging Human Skin

Diseases of the Skin

Purpose: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC. Experimental Design: Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias. Results: Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53 , CDKN2A , NOTCH1 , AJUBA , HRAS , CASP8 , FAT1 , and KMT2C ( MLL3 ). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2 , PARD3 , and RASA1 , were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion. Conclusions: The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC. Clin Cancer Res; 20(24); 6582–92. ©2014 AACR .

https://clincancerres.aacrjournals.org/content/clincanres/20/24/6582.full.pdf

Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma

https://www.gastrojournal.org/article/S0016-5085(11)00864-X/pdf

Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease

Nonmelanoma skin cancer (NMSC) represents the most common form of cancer in Caucasians, with continuing increase in incidence worldwide. Basal cell carcinoma (BCC) accounts for 75% of cases of NMSC, and squamous cell carcinoma (SCC) accounts for the remaining majority of NMSC cases. Whilst metastasis from BCC is extremely rare, metastasis from high-risk SCC may be fatal. In this article, we review the aetiology, diagnosis and management of NMSC.

Nonmelanoma skin cancer

Background Rhinophyma is a progressive, localized or generalized nasal deformity resulting from hypertrophy of sebaceous and connective tissue. The CO(2) laser has been used for treatment of rhinophyma, but the long-term efficacy of the treatment is unknown. Objectives To review the outcome of 124 patients with rhinophyma treated with the CO(2) laser between 1996 and 2008 in our centre. Patients and methods Exuberant sebaceous tissue was ablated using the Sharplan 40C CO(2) laser (Sharplan Lasers UK Ltd, London, U.K.) under local anaesthesia. The technique varied with the severity of rhinophyma; the laser was used in a continuous mode to debulk the larger rhinophymas, and in a resurfacing mode (Silk Touch scanner; Sharplan, 4-7-mm spot at 20-40 W) or continuous mode (10-20 W using a defocused 2-3-mm beam) to reshape the nasal contours. Outcomes were determined by case notes, clinical review and questionnaire. Results Laser treatment was completed in a single session in 115 of 124 patients. All patients were reviewed 3 months post-treatment. Results were classified as good to excellent in 118 and poor in six patients. All patients were sent a satisfaction questionnaire in 2008 and 52 patients replied. Patients reported high levels of satisfaction following treatment. The post-treatment response at 3-month review was maintained long term. The main complications were pain associated with injection of local anaesthetic, scarring and hypopigmentation (four patients) and open pores (two patients). Conclusions The CO(2) laser is an effective and durable treatment for rhinophyma. Treatment carries a low risk of side-effects and is associated with high patient acceptability and satisfaction.

Carbon dioxide laser treatment of rhinophyma: a review of 124 patients.

Cutaneous squamous cell cancer (SCC) is the second most common skin cancer, accounting for one-fifth of all cutaneous malignancies. The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients. This high-risk subgroup of patients can be identified as those with tumors greater than 2 cm in diameter; tumor thickness over 4 mm; moderately/poorly differentiated or desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers; and SCC arising in immunosuppressed patients. It is important to identify and aggressively treat these patients, as high-risk SCC are associated with a greater mortality and morbidity. This article reviews the diagnosis and management of such high-risk SCC.

Management of high-risk squamous cell carcinoma of the skin.

Background Treatment of medium-sized congenital melanocytic naevi (CMN) can be challenging. Objectives To present the results of treatment of 55 CMN with the carbon dioxide (CO2) and pigment-specific lasers. Methods CO2 and Q-switched lasers (frequency-doubled Nd:YAG, Nd:YAG and alexandrite) were used to treat 55 CMN. Patients were treated at 3-month intervals until maximum clearance. Clinical response at 3‐6 months after final treatment was graded as poor ( 75%). Outcomes were evaluated on case note review and questionnaire. Results Thirty-six of the 55 CMN were macular and 19 were mammillated. Twentyseven CMN were present on the head and neck. For macular CMN, outcomes were better for truncal CMN. Scarring and pallor were seen in three lower limb macular CMN treated with a CO2 laser. Mammillated CMN on the head and neck showed most improvement. Pigment-specific lasers were of no additional benefit. Repigmentation occurred in 6% of macular and 21% of mammillated CMN. Partial or complete regimentation of CMN was reported by 46% of patients. Conclusions Compared with macular CMN, mammillated CMN show a marginally better response to laser treatment. CMN on the limbs respond poorly. Pigmentspecific lasers do not lighten mammillated CMN. Adverse effects can occur with CO2 laser treatment of macular CMN on lower limbs.

https://www.naevus-netzwerk.de/wp-content/uploads/August-et-al.-Laser_CMN-BJD-2011.pdf

Vishal Madan

Papers

Non-melanoma skin cancer

Nonmelanoma skin cancer

Carbon dioxide laser treatment of rhinophyma: a review of 124 patients.

Management of high-risk squamous cell carcinoma of the skin.

A study of the efficacy of carbon dioxide and pigment-specific lasers in the treatment of medium-sized congenital melanocytic naevi.