Premenopausal Use of Progestogens and Cutaneous Melanoma Risk: A French Prospective Cohort Study.
- 作者列表："Cervenka I","Al Rahmoun M","Mahamat-Saleh Y","Boutron-Ruault MC","Fournier A","Kvaskoff M
:We investigated the influence of premenopausal use of progestogens on melanoma using data from E3N (Etude Epidémiologique Auprès de Femmes de l'Education Nationale), a prospective cohort of 98,995 French women, aged 40-65 years at inclusion. We used Cox models to adjust for age and melanoma risk factors. Over 1992-2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.02, 1.47), which was reduced after adjustment for melanoma risk factors (HR = 1.15, 95% CI: 0.95, 1.39). There was no heterogeneity across types of progestogens (P = 0.22), and use of multiple progestogens was positively associated with melanoma risk (HR = 1.33, 95% CI: 1.04, 1.70). Among users, we found no relationship with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results.
: 我们使用来自E3N (Etude epid é miologique aupr è s de Femmes de l 'education Nationale) 的数据，研究了绝经前使用孕激素对黑色素瘤的影响，E3N是一个由 98,995 名法国女性组成的前瞻性队列，纳入时年龄 40-65 岁。我们使用Cox模型调整年龄和黑色素瘤风险因素。超过 1992-2008，在 540 名妇女中确定了 79,558 例黑色素瘤病例。我们发现自我报告的孕激素使用与黑色素瘤风险之间存在适度关联 (风险比 (HR) = 1.23，95% 置信区间 (CI) = 1.02，1.47)，在校正黑色素瘤危险因素后，这一比例降低 (HR = 1.15，95% CI: 0.95，1.39)。孕激素类型之间没有异质性 (P = 0.22)，使用多种孕激素与黑色素瘤风险呈正相关 (HR = 1.33，95% CI: 1.04，1.70)。在使用者中，我们没有发现与孕激素使用持续时间、开始和最后一次使用时的年龄以及自第一次和最后一次使用以来的时间有关。尽管我们的结果没有显示阳光暴露的混杂效应的证据，孕激素使用者的住宅阳光暴露水平较低，更有可能报告防晒霜的使用，建议用户特定的阳光暴露配置文件。我们的研究结果不支持孕激素对黑色素瘤风险的强烈影响。需要进一步的研究来证实这些结果。
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.