Smoothened receptor inhibitor vismodegib for the treatment of basal cell carcinoma: a retrospective analysis of efficacy and side effects.
- 作者列表："Bánvölgyi A","Anker P","Lőrincz K","Kiss N","Márton D","Fésűs L","Gyöngyösi N","Wikonkál N
:Background: Smoothened receptor inhibitor vismodegib is indicated to treat locally advanced basal cell carcinoma (laBCC) and lesions in nevoid basal cell carcinoma syndrome (NBCCS).Methods: We treated 11 patients - including four NBCCS and seven laBCC patients - with vismodegib at our department.Results: Complete remission was achieved in three cases, without relapse after discontinuation. Two of the aforementioned patients had NBCCS, in their cases further treatment might be needed. Two patients showed improvement, but later passed away due to unrelated conditions. Two patients with laBCC initially showed remission, then the treatment was suspended due to side effects. After re-administration of the drug, loss of efficacy was observed. We did not observe therapy resistance in our NBCCS group. The rest of the patients showed good response to therapy, but have not reached full remission yet. The main side effects of vismodegib were muscle cramps, dysgeusia, nausea and alopecia. The frequency of adverse events did not show significant differences between the patient groups.Conclusions: Our results show that vismodegib therapy is effective in the treatment of BCC; however, side effects are often severe. Since the suspension of treatment can lead to therapy resistance, the management of side effects is of great importance.
: 背景: Smoothened受体抑制剂vismodegib用于治疗局部晚期基底细胞癌 (laBCC) 和痣样基底细胞癌综合征 (NBCCS) 的病变。方法: 我们在我科用vismodegib治疗了 11 例患者，包括 4 例NBCCS和 7 例laBCC患者。结果: 3 例获得完全缓解，停药后无复发。上述患者中有 2 例患有NBCCS，在他们的病例中可能需要进一步治疗。两名患者显示改善，但后来因无关疾病而去世。2 例laBCC患者最初表现为缓解，随后因副作用暂停治疗。再次给药后，观察到疗效丧失。我们在NBCCS组中未观察到治疗耐药。其余患者对治疗反应良好，但尚未达到完全缓解。Vismodegib的主要副作用是肌肉痉挛、味觉障碍、恶心和脱发。不良事件的频率在患者组之间没有显示出显著差异。结论: 我们的结果表明vismodegib治疗BCC有效; 然而，副作用往往是严重的。由于暂停治疗可导致治疗抵抗，因此副作用的处理非常重要。
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.