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European Journal of Surgical Oncology :... Mar 2024Surgery is the mainstay treatment of melanoma. However, even after radical resection the risk of relapses in majority of stage IIB-IV disease remains high. Currently,... (Review)
Review
Surgery is the mainstay treatment of melanoma. However, even after radical resection the risk of relapses in majority of stage IIB-IV disease remains high. Currently, the standard treatment after surgery in high risk patients is systemic adjuvant therapy administered up to one year based on the results of clinical trials indicating significant reduction of risk of relapses. All clinical trials in adjuvant setting were based as primary end-point on relapse-free survival, not overall survival, and they did not incorporate and validate biomarkers prospectively. A new therapeutic strategy in locoregional advanced melanomas becomes a preoperative treatment to further increase of the cure rates and decrease the duration of systemic therapy.
Topics: Humans; Melanoma; Skin Neoplasms; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Recurrence
PubMed: 38342039
DOI: 10.1016/j.ejso.2024.107969 -
Blood Cancer Journal Aug 2023
Topics: Humans; Clonal Hematopoiesis; Myelodysplastic Syndromes; Myeloproliferative Disorders; Acute Disease; Dendritic Cells; Neoplasms; Skin Neoplasms; Hematologic Neoplasms
PubMed: 37558659
DOI: 10.1038/s41408-023-00893-9 -
Aging Nov 2020Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its...
Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. Overexpression of miR-200b-3p significantly inhibited the proliferation and invasion of melanoma cells. According to bioinformatics analysis and sequencing data, we supposed that SMAD family member 2 (SMAD2) was the target gene and nuclear enriched abundant transcript 1 (NEAT1) was the upstream long non-coding RNA (lncRNA) of miR-200b-3p. These predictions were verified by western blotting and quantitative real-time reverse transcription PCR (RT-qPCR). Luciferase reporter assays revealed that NEAT1 up-regulated SMAD2 by directly sponging miR-200b-3p. and , we demonstrated that both NEAT1 and SMAD2 could promote the proliferation and invasion of melanoma cells, and these effects were reversed by up-regulating miR-200b-3p. In addition, NEAT1/miR-200b-3p/SMAD2 axis promoted melanoma progression by activating EMT signaling pathway and immune responses. Taken together, the NEAT1/miR-200b-3p/SMAD2 signaling pathway promotes melanoma via activation of EMT, cell invasion and is related with immune responses, which provides new insights into the molecular mechanisms and therapeutic targets for melanoma.
Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Databases, Genetic; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Melanoma; MicroRNAs; Neoplasm Invasiveness; RNA, Long Noncoding; Signal Transduction; Skin Neoplasms; Smad2 Protein
PubMed: 33202380
DOI: 10.18632/aging.103909 -
Radiologic Clinics of North America Sep 2021The clinical management of melanoma patients has been rapidly evolving with the introduction of new targeted immuno-oncology (IO) therapeutics. The current diagnostic... (Review)
Review
The clinical management of melanoma patients has been rapidly evolving with the introduction of new targeted immuno-oncology (IO) therapeutics. The current diagnostic paradigms for melanoma patients begins with the histopathologic confirmation of melanoma, initial staging of disease burden with imaging and surgical approaches, treatment monitoring during systemic cytotoxic chemotherapy or IO therapeutics, restaging after completion of adjuvant systemic, surgical, and/or external radiation therapy, and the detection of recurrent malignancy/metastatic disease following therapy. New and evolving imaging approaches with positron-emission tomography (PET) imaging technologies, imaging methodologies, image reconstruction, and image analytics will likely continue to improve tumor detection, tumor characterization, and diagnostic confidence, enabling novel precision nuclear medicine practices for managing melanoma patients. This review will examine current concepts and challenges with existing PET imaging diagnostics for melanoma patients and introduce exciting new opportunities for PET in the current era of IO therapeutics.
Topics: Fluorodeoxyglucose F18; Humans; Melanoma; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Precision Medicine; Radiopharmaceuticals; Skin Neoplasms
PubMed: 34392917
DOI: 10.1016/j.rcl.2021.05.007 -
European Journal of Cancer (Oxford,... Sep 2023Convolutional neural networks (CNNs) have outperformed dermatologists in classifying pigmented skin lesions under artificial conditions. We investigated, for the first...
Diagnostic performance of augmented intelligence with 2D and 3D total body photography and convolutional neural networks in a high-risk population for melanoma under real-world conditions: A new era of skin cancer screening?
BACKGROUND
Convolutional neural networks (CNNs) have outperformed dermatologists in classifying pigmented skin lesions under artificial conditions. We investigated, for the first time, the performance of three-dimensional (3D) and two-dimensional (2D) CNNs and dermatologists in the early detection of melanoma in a real-world setting.
METHODS
In this prospective study, 1690 melanocytic lesions in 143 patients with high-risk criteria for melanoma were evaluated by dermatologists, 2D-FotoFinder-ATBM and 3D-Vectra WB360 total body photography (TBP). Excision was based on the dermatologists' dichotomous decision, an elevated CNN risk score (study-specific malignancy cut-off: FotoFinder >0.5, Vectra >5.0) and/or the second dermatologist's assessment with CNN support. The diagnostic accuracy of the 2D and 3D CNN classification was compared with that of the dermatologists and the augmented intelligence based on histopathology and dermatologists' assessment. Secondary end-points included reproducibility of risk scores and naevus counts per patient by medical staff (gold standard) compared to automated 3D and 2D TBP CNN counts.
RESULTS
The sensitivity, specificity, and receiver operating characteristics area under the curve (ROC-AUC) for risk-score-assessments compared to histopathology of 3D-CNN with 95% confidence intervals (CI) were 90.0%, 64.6% and 0.92 (CI 0.85-1.00), respectively. While dermatologists and augmented intelligence achieved the same sensitivity (90%) and comparable classification ROC-AUC (0.91 [CI 0.80-1.00], 0.88 [CI 0.77-1.00]) with 3D-CNN, their specificity was superior (92.3% and 86.2%, respectively). The 2D-CNN (sensitivity: 70%, specificity: 40%, ROC-AUC: 0.68 [CI 0.46-0.90]) was outperformed by 3D CNN and dermatologists. The 3D-CNN showed a higher correlation coefficient for repeated measurements of 246 lesions (R = 0.89) than the 2D-CNN (R = 0.79). The mean naevus count per patient varied significantly (gold standard: 210 lesions; 3D-CNN: 469; 2D-CNN: 1324; p < 0.0001).
CONCLUSIONS
Our study emphasises the importance of validating the classification of CNNs in real life. The novel 3D-CNN device outperformed the 2D-CNN and achieved comparable sensitivity with dermatologists. The low specificity of CNNs and the lack of automated counting of TBP nevi currently limit the use of augmented intelligence in clinical practice.
Topics: Humans; Reproducibility of Results; Prospective Studies; Dermatologists; Early Detection of Cancer; Skin Neoplasms; Melanoma; Neural Networks, Computer; Nevus; Nevus, Pigmented; Risk Factors; Photography
PubMed: 37453242
DOI: 10.1016/j.ejca.2023.112954 -
International Journal of Molecular... Jan 2020Melanoma is the less common but the most malignant skin cancer. Since the survival rate of melanoma metastasis is about 10-15%, many different studies have been carried... (Review)
Review
Melanoma is the less common but the most malignant skin cancer. Since the survival rate of melanoma metastasis is about 10-15%, many different studies have been carried out in order to find a more effective treatment. Although the development of target-based therapies and immunotherapeutic strategies has improved chances for patient survival, melanoma treatment still remains a big challenge for oncologists. Here, we collect recent data about the emerging role of melanoma-associated microRNAs (miRNAs) currently available treatments, and their involvement in drug resistance. We also reviewed miRNAs as prognostic factors, because of their chemical stability and resistance to RNase activity, in melanoma progression. Moreover, despite miRNAs being considered small conserved regulators with the limitation of target specificity, we outline the dual role of melanoma-associated miRNAs, as oncogenic and/or tumor suppressive factors, compared to other tumors.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Drug Resistance, Neoplasm; Humans; Immunotherapy; Melanoma; MicroRNAs; Microphthalmia-Associated Transcription Factor; Risk Factors; Skin Neoplasms
PubMed: 32013263
DOI: 10.3390/ijms21030878 -
International Wound Journal May 2022The study spotlights a severe uncommon post-burn complication, Marjolin's ulcer, in upper Egypt plastic and wound care centres. This problem is mainly related to... (Review)
Review
The study spotlights a severe uncommon post-burn complication, Marjolin's ulcer, in upper Egypt plastic and wound care centres. This problem is mainly related to inadequate medical care and awareness. No community or race is immune. The underlying malignant transformation mechanism remains unclear. The study aims, according to our experience, to review the prognostic factors through the management protocol of Marjolin's ulcers. This prospective study was conducted in the Aswan University Plastic & Burn surgery department in South Egypt between 2013 and 2020 and investigated 226 patients with chronic post-burn ulceration. Nineteen cases were proved to have Marjolin's ulcer, and the other cases that had been excluded from being malignant went for reconstruction with split-thickness skin graft with/without flap after adequate ulcer debridement. The surgical, oncologic, radiologic indications, and prognostic factors were reviewed according to our management outcome-the assessment with follow-up period extended over 5 years. Histopathology of ulcers ranged among mild, moderate, and poorly differentiated squamous cell carcinoma. One scalp ulcer case showed basosquamous pathology. Most cases presented at age above 50, but no age was immune. The mean latent period was 29 years on average. The lesions' sites varied in their anatomic location where they involved the upper extremity, the scalp, and the lower extremity that had a predilection. Although surgical excision is the primary management line for tumour ablation, other factors may change the management course. During the follow-up period, neoplasm recurrence in the form of lymph node enlargement and/or locoregional metastasis was detected in eight cases. Within 1 year after the intervention, six recurrent cases died, and two were saved. In addition to the case study, this paper reviewed the literature and provided our team a good experience in light of the NCCN protocol for non-melanotic cutaneous carcinoma, although we suffered limited medical resources. It is concluded that early accurate diagnosis, low-grade malignancy, and well-planned individualised surgery with adjuvant radiotherapy were the best prognostic factors. The close follow-up for an early sign of disease recurrence is paramount.
Topics: Carcinoma, Squamous Cell; Cicatrix; Humans; Neoplasm Recurrence, Local; Plastics; Prospective Studies; Skin Neoplasms; Skin Ulcer; Ulcer
PubMed: 34535972
DOI: 10.1111/iwj.13690 -
Medical Sciences (Basel, Switzerland) Sep 2021Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From...
Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002-2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03-1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies.
Topics: Aged; Female; Humans; Lymph Node Excision; Male; Melanoma; Middle Aged; Nail Diseases; Neoplasm Recurrence, Local; Retrospective Studies; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 34564082
DOI: 10.3390/medsci9030057 -
Acta Dermato-venereologica Jan 2020Most patients with mycosis fungoides are diagnosed with early-stage disease. However, prevalence of early-stage disease is unknown, and evidence of its burden is scarce....
Most patients with mycosis fungoides are diagnosed with early-stage disease. However, prevalence of early-stage disease is unknown, and evidence of its burden is scarce. The aim of this study is to estimate the prevalence of early-stage mycosis fungoides, how long patients live with early-stage disease and to characterise these patients. Data were obtained from 4 key publications and from US cancer registries (Surveillance, Epidemiology and End Results Program; SEER). The derived incidence of early-stage mycosis fungoides was 0.26/100,000 (UK), 0.29/100,000 (US) and 0.38/100,000 (US-SEER) and the prevalence was 4.8/100,000 (UK), 5.2/100,000 (US) and 6.6/100,000 (US-SEER). Early-stage disease may last for 18 years. From SEER registries, 3,132 were diagnosed at early stage (mostly stage IA). Median age at diagnosis was 58 years. Compared with stage IA, the relative risk of death was 1.3 for stage IB and 3.5 for stage IIA. We confirm the rarity of early-stage mycosis fungoides, a differential prognosis and the potential for elevated burden of disease.
Topics: Disease Progression; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Prognosis; Skin Neoplasms
PubMed: 31663598
DOI: 10.2340/00015555-3367 -
Journal of Internal Medicine Dec 2020The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including... (Review)
Review
The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. Intralesional BCG (IL-BCG) immunotherapy is a highly efficient and cost-effective treatment option for inoperable stage III in-transit melanoma, as recommended in the National Comprehensive Cancer Network Guidelines. IL-BCG has shown great efficacy in the regression of directly injected metastatic melanoma lesions, as well as distal noninjected nodules in immunocompetent patients. Clinical and preclinical studies have shown that BCG serves as a strong immune modulator, inducing the recruitment of various immune cells that contribute to antitumour immunity. However, the specific mechanism of BCG-mediated tumour immunity remains poorly understood. Comparative genome analyses have revealed that different BCG strains exhibit distinct immunological activity and virulence, which might impact the therapeutic response and clinical outcome of patients. In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Animals; Antineoplastic Agents, Immunological; BCG Vaccine; Humans; Immunity, Innate; Melanoma; Mycobacterium bovis; Neoplasm Metastasis; Neoplasm Staging; Neoplasms; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 32128919
DOI: 10.1111/joim.13037