Performance of models predicting residual lymph node disease in melanoma patients following sentinel lymph node biopsy.
- 作者列表："MacDonald S","Siever J","Baliski C
BACKGROUND:Among melanoma patients with a tumor-positive sentinel node biopsy (SNB), approximately 20% harbor disease in non-sentinel nodes (nSN), as determined by a completion lymph node dissection (CLND). CLND lacks a survival benefit and has high morbidity. This study assesses predictive factors for nSN metastasis and validates five models predicting nSN metastasis. METHODS:Patients with invasive melanoma were identified from the BC Cancer Agency (2005-2015). Clinicopathological data were collected from 296 patients who underwent a CLND after a positive SNB. Multivariate analysis was completed to assess predictive variables in the study population. Five models were externally validated using overall model performance (Brier score [calibration and discrimination]) and discrimination (area under the ROC curve [AUC]). RESULTS:Seventy-three patients had nSN metastasis at the time of CLND. The variable most predictive of nSN involvement was lymphovascular invasion (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.67-9.54; p = 0.002). The highest discrimination was Lee et al. (2004) (AUC 0.68 [95% CI 0.61-0.75]), Rossi et al. (2018) (AUC 0.68 [95% CI 0.57-0.77]), and Bertolli et al. (2019) (AUC 0.68 [95% CI 0.60-0.75]). Rossi et al. (2018) had the lowest overall model performance (Brier score 0.44). Rossi et al. (2018) and Bertolli et al. (2019) had the ability to stratify patients to a risk of nSN involvement up to 99% and 95%, respectively. CONCLUSION:Bertolli et al. (2019) had amongst the highest overall model performance, was the most clinically meaningful and is recommended as the preferred model for predicting nSN metastasis.
背景: 在肿瘤阳性前哨淋巴结活检 (SNB) 的黑色素瘤患者中，大约 20% 的非前哨淋巴结 (nSN) 存在疾病，通过完成淋巴结清扫 (CLND) 确定。CLND缺乏生存获益，发病率高。本研究评估了nSN转移的预测因素，并验证了预测nSN转移的 5 个模型。 方法: 从BC癌症机构 (2005-2015) 确定侵袭性黑色素瘤患者。收集 296 例SNB阳性后接受CLND的患者的临床病理资料。完成多变量分析以评估研究人群中的预测变量。使用总体模型性能 (Brier评分 [校准和辨别]) 和辨别 (ROC曲线下面积 [AUC]) 对 5 个模型进行了外部验证。 结果: 73 例患者在CLND时出现nSN转移。NSN受累的最预测变量是淋巴管侵犯 (比值比 [OR] 3.99; 95% 置信区间 [CI] 1.67-9.54; p = 0.002)。最高的区分度为Lee et al. (2004) (AUC 0.68 [95% CI 0.61-0.75])，Rossi et al. (2018) (AUC 0.68 [95% CI 0.57-0.77])，和Bertolli等 (2019) (AUC 0.68 [95% CI 0.60-0.75])。Rossi等 (2018) 的总体模型性能最低 (Brier评分 0.44)。Rossi et al. (2018) 和Bertolli et al. (2019) 有能力将患者分层为nSN受累风险分别高达 99% 和 95%。 结论: Bertolli et al. (2019) 具有最高的总体模型性能，是最具临床意义的，被推荐为预测nSN转移的首选模型。
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.