No abstract

Malignant peripheral nerve sheath tumors (MPNST) develop in ~10% of neurofibromatosis type-1 patients and are a major contributing factor to neurofibromatosis-1 patient mortality and morbidity. MPNSTs are multidrug resistant, and thus long-term patient survival rates are poor after standard doxorubicin or multiagent chemotherapies. We show that the hyaluronan receptor CD44 forms complexes with multidrug transporters, BCRP (ABCG2) and P-glycoprotein (ABCB1), in the plasma membrane of human MPNST cells. Small hyaluronan oligosaccharides antagonize hyaluronan-CD44–mediated processes and inhibit hyaluronan production. Treatment of MPNST cells with the hyaluronan oligomers causes disassembly of CD44-transporter complexes and induces internalization of CD44, BCRP, and P-glycoprotein. Consequently, the oligomers suppress drug transporter activity and increase sensitivity to doxorubicin treatment in culture. In vivo, systemic administration of hyaluronan oligomers inhibits growth of MPNST xenografts. Moreover, the oligomers and doxorubicin act synergistically in vivo, in that combined suboptimal doses induce tumor regression to a greater extent than the additive effects of each agent alone. These findings indicate that constitutive hyaluronan-CD44 interactions contribute to drug transporter localization and function at the plasma membrane, and that attenuating hyaluronan-CD44 interactions sensitizes MPNSTs to doxorubicin in vitro and in vivo. These results also show the potential efficacy of hyaluronan oligomers, which are nontoxic and nonimmunogenic, as an adjuvant for chemotherapy in MPNST patients.

Sebaceous carcinoma is a rare and potentially aggressive cutaneous malignancy. Commonly reported in the periocular area and the head and neck region, sebaceous carcinoma can arise from any sebaceous gland in the skin. The clinical presentation may be nonspecific, and a biopsy is important to establish a diagnosis and to differentiate from mimickers including benign sebaceous neoplasms, other adnexal tumors, and basal cell carcinoma. A diagnosis of Muir Torre syndrome should be considered in patients presenting with a sebaceous neoplasm. Early treatment is important given the potential of sebaceous carcinoma to spread to the regional lymph nodes and beyond. Sentinel lymph node biopsy and imaging to complete tumor staging may be indicated for larger or more aggressive tumors. Surgery, including Mohs micrographic surgery, remains the primary treatment modality for sebaceous carcinoma. Mohs micrographic surgery has the advantage of complete margin evaluation and low recurrence rates. Advanced cases may be treated with orbital exenteration, radiation therapy, chemotherapy, or combination therapy.

There is increasing evidence that the intestinal microbiome plays an important role in modulating systemic inflammation and disease. Oral probiotics can modulate the intestinal microbiome and have demonstrated to be efficacious in treating topical skin conditions, such as atopic dermatitis, acne and rosacea. By proxy, exogenous application to the skin of probiotics should also promote a positive bacterial balance to mitigate or potentially eliminate pathologic conditions. The goal of this article was to provide a systematic review of studies that have investigated the role of topical probiotics in mitigating skin conditions. Additionally, skin conditions where dysbiosis has been identified but topical probiotics have not been investigated are discussed. We hope this review both analyses the evidence for the role that topical probiotics could play in topical skin conditions and highlights additional areas in need of research and exploration.

Pathogenic, opportunistic, and commensal bacterial coexist in the intestinal tract, and imbalances among these strains have been linked to systemic inflammation and a variety of disease states. Similarly, human skin plays an important role as an interface between the body and the environment with an estimated 1 billion microbes per square centimetres. Skin microbiome fluctuations that cause increases in pathologic bacteria, either because of individual and/or environmental factors, can lead to disease states at the skin level ranging from inflammatory conditions to infections. As wounds are inherently associated with perturbations in the local microflora due to injury and activation of the immune responses, the addition of topical probiotics could be a means to prevent infection, regulate inflammation, and potentially augment healing. The goal of this review is to analyse the impact the skin microbiome has on cutaneous wound healing with a focus on developing proposed treatment algorithms and support for their therapeutic potential.

No abstract

BACKGROUND Limited information exists on the demographics, tumor characteristics, and treatment in primary cutaneous mucinous carcinoma (PCMC). OBJECTIVE The authors sought to describe prognostic factors, incidence rates, and the subsequent primary malignancy (SPM) risk in patients with PCMC. METHODS Primary cutaneous mucinous carcinoma cases in the National Cancer Institute's Surveillance, Epidemiology, and End Results data (1972–2013) were analyzed to provide demographic, cancer-related, and treatment information and to calculate incidence and mortality. Patients were stratified by stage (local, regional, distant disease) for comparison. The risk of developing an SPM was calculated. RESULTS Four hundred eleven PCMC cases were identified. The age-adjusted incidence was 0.04 cases per 100,000-person years. Blacks were disproportionately affected by PCMC (0.048; 95% confidence interval, 0.034–0.065; p < .001). Approximately 67.4% of patients had local disease, 10.5% had regional disease, and 5.8% had distant disease. Primary cutaneous mucinous carcinoma–specific mortality was independent of sex, age, race, primary site, histologic tumor grade, tumor size, tumor stage, or treatment. The overall frequency of developing a second primary malignancy was not increased in patients with PCMC. CONCLUSION Although PCMC occurs with equally in both sexes, it may be more common in African Americans than previously recognized. Although eyelid PCMC may have a higher rate of distant metastasis, all patients need close follow-up.

In the past, hypertrophic lichen planus and SCC have been considered isolated diseases. Based on an increasing number of cases, the association between hypertrophic lichen planus and keratinocyte malignancies warrants surveillance.