The role of cyclin D1 and Ki-67 in the development and prognostication of thin melanoma.

AIMS: Despite their low individual metastatic potential, thin melanomas (≤1 mm Breslow thickness) contribute significantly to melanoma mortality overall. Therefore, identification of prognostic biomarkers is particularly important in this subgroup of melanoma. Prompted by preclinical results, we investigated cyclin D1 protein and Ki-67 expression in in-situ, metastatic and non-metastatic thin melanomas. METHODS AND RESULTS: Immunohistochemistry was performed on 112 melanoma specimens, comprising 22 in situ, 48 non-metastatic and 42 metastatic thin melanomas. Overall, epidermal and dermal cyclin D1 and Ki-67 expression were semiquantitatively evaluated by three independent investigators and compared between groups. Epidermal Ki-67 expression did not differ statistically in in-situ and invasive melanoma (P = 0.7). Epidermal cyclin D1 expression was significantly higher in thin invasive than in in-situ melanoma (P = 0.003). No difference was found in cyclin D1 expression between metastatic and non-metastatic invasive tumours. Metastatic and non-metastatic thin melanomas did not show significant differences in epidermal expression of Ki-67 and cyclin D1 (P = 0.148 and P = 0.611, respectively). In contrast, strong dermal expression of Ki-67 was more frequent in metastatic than non-metastatic samples (28.6 versus 8.3%, respectively, P = 0.001). The prognostic value of dermal Ki-67 expression was confirmed by multivariate analysis (P = 0.047). CONCLUSION: We found an increased expression of cyclin D1 in invasive thin melanomas compared to in-situ melanomas, which supports a potential role of this protein in early invasion in melanoma, as suggested by preclinical findings. Moreover, our results confirm that high dermal Ki-67 expression is associated with an increased risk of development of metastasis in thin melanoma and could possibly serve as a prognostic biomarker in clinical practice, especially if combined with additional methods.

Outcome after out-of-hospital ventricular fibrillation or pulseless ventricular tachycardia: comparison of before and after the implementation of the 2010 Guidelines in a single centre.

AIMS OF THE STUDY: Improvements to guidelines and efforts to train and equip laypersons and medical professionals are expected to result in improvements in the outcomes of patients experiencing out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate changes in the survival and neurological outcomes of patients before and after the implementation of the 2010 guidelines. METHODS: In a retrospective chart review, we analysed the outcomes of 182 patients who suffered bystander-witnessed, out-of-hospital ventricular fibrillation or pulseless ventricular tachycardia of cardiac aetiology. These definitions were based on the Utstein style. Survival at hospital discharge (study period 2006 to 2015), 1-year survival (study period 2011 to 2015), neurological outcome (cerebral performance category [CPC] score) and the corresponding changes over time were evaluated. In addition, the results were compared with results obtained from a systematic review of the literature. RESULTS: Of 1423 confirmed OHCAs, 182 fulfilled our inclusion criteria. 91 were treated between 2006 and 2010, and 91 from 2011 to 2015. Thirty-one (34%) survived until hospital discharge in the first time period, 44 (48%) in the second time period (p = 0.071); 26/31 (83%) and 40/44 (91%) respectively had a CPC score of 1–2. Between 2011 and 2015, the 1-year survival rate of the patients discharged from hospital was 36/44 (82%). All of these 36 patients (100%) had a favourable neurological outcome (CPC 1–2). These results were well within the range reported in the literature, although this range is wide (11 to 52% for survival at discharge and 6 to 47% for survival at 1 year). CONCLUSIONS: Survival was found to be at the upper range of the results retrieved by the systematic literature review. However, we found no significant improvements over time. The neurological outcomes of the survivors were favourable. The generalisability of this study is limited by its small sample size. To further improve outcomes, more public health measures, such as a functioning chain of survival, are required (e.g. an effective first responder network).

Multicenter, real-life experience with checkpoint inhibitors and targeted therapy agents in advanced melanoma patients in Switzerland.

Metastatic melanoma is a highly aggressive disease. Recent progress in immunotherapy (IT) and targeted therapy (TT) has led to significant improvements in response and survival rates in metastatic melanoma patients. The current project aims to determine the benefit of the introduction of these new therapies in advanced melanoma across several regions of Switzerland. This is a retrospective multicenter analysis of 395 advanced melanoma patients treated with standard chemotherapy, checkpoint inhibitors, and kinase inhibitors from January 2008 until December 2014. The 1-year survival was 69% (n=121) in patients treated with checkpoint inhibitors (IT), 50% in patients treated with TTs (n=113), 85% in the IT+TT group (n=66), and 38% in patients treated with standard chemotherapy (n=95). The median overall survival (mOS) from first systemic treatment in the entire study cohort was 16.9 months. mOS of patients treated either with checkpoint or kinase inhibitors (n=300, 14.6 months) between 2008 and 2014 was significantly improved (P<0.0001) compared with patients treated with standard chemotherapy in 2008-2009 (n=95, 7.4 months). mOS of 61 patients with brain metastases at stage IV was 8.1 versus 12.5 months for patients without at stage IV (n=334), therefore being significantly different (P=0.00065). Furthermore, a significant reduction in hospitalization duration compared with chemotherapy was noted. Treatment with checkpoint and kinase inhibitors beyond clinical trials significantly improves the mOS in real life and the results are consistent with published prospective trial data.