- 作者列表："Lee AY","Berman RS
:Surgery with or without radiation has always been the mainstay of treatment for patients with non-melanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. Until recently, there were no effective systemic therapies for patients with advanced disease. This review will focus on the landmark clinical trials that led to Food and Drug Administration (FDA) approval of Vismodegib for advanced basal cell carcinoma (ERIVANCE BCC) and pembrolizumab for advanced Merkel cell carcinoma (KEYNOTE-017). These trials have not only changed the landscape for patients with metastatic disease but also notably for patients with locally advanced disease that is either unresectable or resectable with high morbidity. Additional mention is made for the clinical trial that led to FDA approval of cemiplimab for advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1), which is already changing practice patterns, but for which longer-term data are still needed.
: 手术加或不加放疗一直是非黑色素瘤皮肤癌患者的主要治疗手段，包括基底细胞癌、鳞状细胞癌和Merkel细胞癌。直到最近，对于晚期疾病患者还没有有效的全身治疗方法。这篇综述将集中在导致Vismodegib批准用于晚期基底细胞癌 (ERIVANCE BCC) 的具有里程碑意义的临床试验上和pembrolizumab治疗晚期Merkel细胞癌 (KEYNOTE-017)。这些试验不仅改变了转移性疾病患者的景观，而且显著地改变了不能切除或可切除且发病率高的局部晚期疾病患者的景观。还提到了导致FDA批准cemitlimab治疗晚期皮肤鳞状细胞癌 (EMPOWER-CSCC-1) 的临床试验，该试验已经在改变实践模式，但是仍然需要更长期的数据。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.