- 作者列表："Robinson AV","Keeble C","Lo MCI","Thornton O","Peach H","Moncrieff MDS","Dewar DJ","Wade RG
OBJECTIVES:The neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease. METHODS:This multicentre cohort study describes patients treated for Stage I-III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression. RESULTS:Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p < 0.001). A baseline NLR ≥ 2.3 was associated with 30% higher odds of microscopic metastatic melanoma in the sentinel lymph node [adjusted OR 1.3 (95% CI 1.3, 1.3)]. Following surgery, 253 patients (18.7%) developed recurrent melanoma during surveillance although there was no statistically significant association between the baseline NLR and the risk of recurrence [adjusted HR 0.9 (0.7, 1.1)]. CONCLUSION:The NLR is associated with the volume of melanoma at presentation and may predict occult sentinel lymph metastases. Further prospective work is required to investigate how NLR may be modelled against other clinicopathological variables to predict outcomes and to understand the temporal changes in NLR following surgery for melanoma.
目的: 中性粒细胞-淋巴细胞比率 (NLR) 是一种炎性生物标志物，可用于癌症预后。我们旨在研究局限性和转移性皮肤黑色素瘤患者之间基线NLR的差异，以及随着疾病复发，该生物标志物如何随时间变化。 方法: 这项多中心队列研究描述了 10 年间接受I-III期皮肤黑色素瘤治疗的患者。术前立即测量基线NLR，出院或疾病复发时再次测量。使用混合效应logistic回归估计前哨淋巴结受累的比值比 (OR)。使用多变量Cox回归估计复发风险。 结果: 共纳入 1489 例个体。触诊淋巴结疾病患者的平均基线NLR高于显微镜下淋巴结或局部疾病患者 (分别为 2.8 vs 2.4 和 2.3; P <0.001)。基线nlr ≥ 2.3 与前哨淋巴结微小转移性黑色素瘤的发生率高 30% 相关 [校正OR 1.3 (95% CI 1.3，1.3)]。手术后，253 例患者 (18.7%) 在监测期间发生复发性黑色素瘤，尽管基线NLR与复发风险之间无统计学显著相关性 [校正HR 0.9 (0.7，1.1)]。 结论: NLR与就诊时黑色素瘤的体积相关，并可能预测隐匿性前哨淋巴结转移。需要进一步的前瞻性工作来研究NLR如何与其他临床病理变量进行建模，以预测结果，并了解黑色素瘤手术后NLR的时间变化。
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.