Melanoma in older patients: declining gap in survival between younger and older patients with melanoma.
- 作者列表："Schuurman MS","Hollestein LM","Bastiaannet E","Posthuma EFM","van Akkooi AJC","Kukutsch NA","Aarts MJB","Wakkee M","Lemmens VEPP","Louwman MWJ
:Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades.Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 (n = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conductedResults: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89).Conclusion: The gap in melanoma incidence between younger and older people is increasing due to a strong increase in incidence in older adults. Disparities in survival are declining, related to a narrowing gap in Breslow thickness.
背景: 老年人黑色素瘤的发病率最高，在大多数西方国家人口正在老龄化。我们评估了过去几十年中年轻患者和老年患者之间的发病率和生存率差距是如何发展的。材料和方法: 1989 年至 2015 年间诊断为皮肤黑色素瘤的所有患者 (n = 84,827) 均来自荷兰癌症登记处。老年人定义为年龄 ≥ 70 岁。描述了患者和肿瘤特征的差异，计算了年龄特异性发病率，并进行了相对生存率 (RS) 和估计相对超额死亡率 (RER) 的多变量分析。结果: 在老年男性中，黑色素瘤的年龄标准化发病率从 18 增加到 103/100，000 人-年 (py)1989 年至 2015 年之间，老年女性 23 ~ 70/100 py。在年轻男性和女性中，它分别从 8 增加到 21，从 13 增加到 28/100 py。老年男性和女性的Breslow厚度中位数从 1.8 下降到 1.1，从 1.6 下降到 1.1 (2003 对 2015)，从 1.1 到 0.9 毫米和 0.9 到 0.8 毫米的年轻男女。在老年男性中，5 年RS从 67%-95% 年的 63% (72% CI: 1989-1997) 增加到 85% (95% CI: 83%-87%) 在 2007-2015 和老年女性中，从 81% (95% CI: 78%-85%) 到 89% (95% CI: 87%-91%)。在年轻男性和女性中，RS从 82% (95% CI: 81%-83%) 增加到 90% (95% CI: 90%-91%) 和从 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%)。病例组合校正后，老年男性和女性随着时间的推移不再表现出生存率的改善 (RER 2010-2015 vs 2003-2009: 0.97; 95% CI: 0.81-1.16 和 0.95; 95% CI: 0.79-1.16)。而年轻男性和女性的生存率仍然提高 (RER 0.75; 95% CI: 0.67-0.83 和 0.77; 95% CI: 0.67-0.89)。结论: 由于老年人的发病率急剧增加，年轻人和老年人之间黑色素瘤发病率的差距正在增加。生存率差异正在下降，与Breslow厚度差距缩小有关。
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.