Loss of Concurrent Regulation of the Expression of BIF-1, BAX, and Beclin-1 in Primary and Metastatic Melanoma.

Melanoma is one of the most aggressive and drug-resistant cancers. Despite novel promising therapeutic strategies, the prognosis of metastatic melanoma patients remains poor and it is often associated with high relapse rates. Endophilin B1, also known as BIF-1, is a multifunctional protein involved in several biological processes such as autophagy and apoptosis. BIF-1 promotes apoptosis through binding to BAX and its translocation to the mitochondrial outer membrane. On the other hand, BIF-1 can interact with Beclin-1 through UVRAG to promote autophagy. Several reports suggest an ambiguous role of BIF-1 in cancer development and progression. For example, it has been demonstrated that the expression of BIF-1 is reduced in both primary and metastatic melanoma and that the reduction of BIF-1 expression is associated with reduced overall survival of melanoma patients. Here we show that the expression of Beclin-1 and active form of BAX are also reduced in the melanoma patients. However, while we observed strong positive correlations between the expression of BIF-1 and Beclin-1 as well as between BIF-1 and BAX in benign nevi, these correlations were lost in the primary and metastatic melanoma cells. These data indicate disruption in the proximal molecular mechanisms which regulate expression of BIF-1, Beclin-1, and BAX in the primary and metastatic melanoma.

Melanoma of the nail apparatus: a systematic review and meta-analysis of current challenges and prognosis.

Nail apparatus melanoma (NAM) is a rare dermatologic malignancy. Its prognosis is poor because it is often diagnosed late. However, progression and survival of NAM patients have only been studied among small populations. Early biopsy could help to identify suspicious lesions at a less invasive stage. While surgery is generally seen as the treatment of choice, the extent of excision margins and the use of sentinel biopsy remain debated. This systematic review aims to summarize the treatment procedures and observed prognosis in the literature during the last two decades and present pooled survival and progression rates of NAM by using meta-analysis. A systematic review on studies assessing pathology, treatment and prognosis of NAM was carried out up to end of 2018. After evaluation of eligible studies, the main emerging topics were outlined and pooled survival outcomes estimated. A total of 30 articles out of 624 identified records were included for systematic review. Finally, meta-analysis of pooled mortality rates including 18 studies was 4.6 × 100 patient-years (95% CI: 2.7, 6.8) equivalent to 5-year cumulative survival of 77.0%. Additionally, the pooled progression rate based on 17 studies was 6.3 × 100 patient-years (95% CI: 4.1, 8.9) with estimated 5-year cumulative progression-free survival of 68.5%. While the optimal extent of surgical treatment remains debated, prompt biopsy could help to identify early lesions. This is the first study to present pooled survival and progression rates by meta-analysis.

New approach for virtual surgical planning and mandibular reconstruction using a fibula free flap.

Maxillofacial reconstruction poses a major challenge to surgeons because of the associated anatomical complexity, the sensitivity of the involved systems and the need to maintain a pleasing facial appearance. Here, we present a detailed description of a new method for extensive mandibular reconstruction using open-source virtual design software and a desktop 3D printer. A surgeon segmented preoperative computed tomography angiography scans with the Amira program to create a digital model of the mandible, skull and fibula. These datasets were imported into Blender, an open-source computer-aided design software package, where arrangement of the fibula segments into aligned sections was performed. Then, a desktop 3D printer was used to produce a reconstructed mandible. After fixation of a plate onto the reconstructed mandible, cutting guides were digitally designed using Blender. Following this, the surgeon performed mandible resection using the fixed cutting guides, which were 3D-printed using biocompatible plastic (Med 610/Stratasys Inc.) and fixed to the prebent reconstructed mandible at a predetermined position. After cutting the fibula with the help of the cutting guides and aligning the fibular segments into mandibular space, the surgeon fixed the segments to the reconstruction plate. Postoperatively, multislice computed tomography scans were taken for control purposes. Our method for mandibular reconstruction offers the following benefits: shorter operation planning time, increased accuracy during osteotomy through the use of a special fibula cutting guide and low costs. In brief, this method is an easy, precise and highly flexible technique for mandibular reconstruction with a fibula flap.

In vivo confocal microscopy efficacy assessment of daylight photodynamic therapy in actinic keratosis patients.

BACKGROUND: Reflectance confocal microscopy (RCM) is a noninvasive diagnostic technique with an acceptable sensitivity and specificity for actinic keratosis (AK). OBJECTIVES: We evaluated efficacy of daylight photodynamic therapy (DL-PDT) in patients with AK using a new RCM atypia scoring system. MATERIALS AND METHODS: All patients with AK lesions (Grade I-II) were included in our study (2012-15). Baseline clinical, dermoscopy and RCM evaluations were followed by DL-PDT. In the first follow-up, clinical examination, dermoscopy and RCM imaging of the treated area were carried out. Atypia scoring and cell size measurements were used to compare before and after RCM images. RESULTS: From 40 lesions (20 patients with mean age of 75·5 years), complete resolution and partial response of the actinic damage was detected in 80% and 17·5% of lesions, respectively. No cellular atypia was seen in the follow-up RCM images of 57·5% of lesions (n = 23), while in 40% of lesions (n = 16) minimal changes to the honeycomb pattern of the epidermis were seen in the follow-up RCM images (atypia score 1). Only one lesion showed minimal or no clinical response, and a persistent moderate amount of atypia in RCM. Furthermore, atypia score and mean cell size decreased significantly in the follow-up DL-PDT RCM images (P < 0·001, P = 0·001, respectively). CONCLUSIONS: RCM features of actinic damage at cellular level have been shown to correlate well with the results of a clinical assessment of AK lesions. This study confirms that in vivo RCM technology might be an additional technique to monitor the efficacy of DL-PDT for AK.

Excision of fascia in melanoma thicker than 2 mm: no evidence for improved clinical outcome.

BACKGROUND: Lack of evidence-based data causes significant variation among surgeons concerning the depth of wide excision for primary cutaneous melanomas. OBJECTIVES: To evaluate the clinical effect of excision of the deep fascia in melanomas thicker than 2 mm on patient outcome. METHODS: We performed a retrospective cohort review (1996-2012) of patients with melanomas thicker than 2 mm. Included patients underwent excision with a 1-cm margin. Data collected included the patients' sex, age, tumour location, tumour type, Breslow depth and presence of ulceration. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were compared between the fascia-excised and the fascia-preserved groups. RESULTS: Out of 2182 patients with malignant melanomas, 213 melanomas thicker than 2 mm, with a median follow-up of 1547 days, were included. The mean age of the patients was 62·6 years and the mean Breslow depth was 4·2 mm. Analysis of data for death attributable to melanoma (P = 0·72), local recurrence (P = 0·71), and locoregional (P = 0·87) and distant metastases (P = 0·34) were not significantly different between the study groups. Furthermore, Kaplan-Meier and Cox regression analysis of both groups showed no evidence of significant difference regarding disease-free [P = 0·35; hazard ratio (HR) 1·25; 95% confidence interval (CI) 0·79-1·97] and overall survival (P = 0·63; HR 1·18; 95% CI 0·61-2·27). CONCLUSIONS: We believe that excision of the deep fascia does not improve the outcome of melanomas thicker than 2 mm.