Treatment of advanced melanoma has undergone a paradigm shift over the last 10–15 years. The frustrating results of studies on medical treatment ten years ago have been replaced by studies constantly ...improving survival in patients with advanced melanoma. Immune checkpoint inhibitors belong to one group of treatments and targeted therapy to another. Fifty percent of melanomas are BRAF mutation positive. Normally, the mitogen activated protein kinase or MAP kinase (Ras-BRAF-MEK-Erk chain) pathways translate external signals to intracellular growth and proliferation. In BRAF mutated melanoma cells, the mutated BRAF kinase is excessively active leading to autonomous proliferation and cancerous growth. This kinase can be blocked by BRAF-inhibitors. If given to BRAF negative melanoma patients, it may lead to disease progression because Ras is not inhibited in these cells. Development of Squamous cell carcinomas as a serious adverse event to BRAF inhibition may be caused by similar mechanisms in non BRAF mutated keratinocytes. A spontaneous and paradoxical loss of effect is seen with BRAF inhibitors due to various ways melanoma cells bypass BRAF. This is somewhat counteracted by the addition of a MEK1/2 inhibitor. Overall progression-free survival has increased from a median of two months for chemotherapy, via 7–8 months for BRAF inhibitor to 10–14 months for newer BRAF and MEK inhibitor combination therapy.
Halo naevi are considered benign. They occur in children and adolescents. Eruptive multiple halo naevi are infrequently seen in adults. The first patient in this case series had previously had ...melanoma. Positron emission tomography-computed tomography (PET-CT) showed a papillary thyroid carcinoma. Subsequent adult patients underwent an examination programme similar to melanoma patients with unknown primary, including PET scanning. Sixteen patients were followed over a 6-year period. In total there were 2 papillary thyroid cancers, 1 neuroendocrine lung tumour, 1 patient had had lung metastases from a thin melanoma 7 years previously, 3 patients had primary cutaneous melanoma (1 had had halo naevi since excision of 2 melanomas 15 years previously) and 1 had melanoma metastasis with unknown primary. The incidence of melanoma was 955 times higher than expected (standardized incidence rate). The benefits of PET scanning must be validated in a controlled trial prior to implementation into clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We investigate a method of updating a Danish monolingual dictionary with new semantic information on already included lemmas in a systematic way, based on the hypothesis that the variation in bigrams ...over time in a corpus might indicate changes in the meaning of one of the words. The method combines corpus statistics with manual annotations. The first step consists in measuring the collocational change in a homogeneous newswire corpus with texts from a 14 year time span, 2005 through 2018, by calculating all the statistically significant bigrams. These are then applied to a new version of the corpus that is split into one sub-corpus per year. We then collect all the bigrams that do not appear at all in the first three years, but appear at least 20 times in the following 11 years. The output, a dataset of 745 bigrams considered to be potentially new in Danish, are double annotated, and depending on the annotations and the inter-annotator agreement, either discarded or divided into groups of relevant data for further investigation. We then carry out a more thorough lexicographical study of the bigrams in order to determine the degree to which they support the identification of new senses and lead to revised sense inventories for at least one of the words Furthermore we study the relation between the revisions carried out, the annotation values and the degree of inter-annotator agreement. Finally, we compare the resulting updates of the dictionary with Cook et al. (2013), and discuss whether the method might lead to a more consistent way of revising and updating the dictionary in the future.
The Danish Melanoma Database Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva ...
Clinical epidemiology,
01/2016, Letnik:
8
Journal Article
Recenzirano
Odprti dostop
The aim of the database is to monitor and improve the treatment and survival of melanoma patients.
All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish ...Melanoma Database (DMD). In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register.
The main variables include demographic, clinical, and pathological characteristics, including Breslow's tumor thickness, ± ulceration, mitoses, and tumor-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly.
The DMD is an old research database, but new as a clinical quality register. The coverage is high, and the performance in the five Danish regions is quite similar due to strong adherence to guidelines provided by the Danish Melanoma Group. The list of monitored indicators is constantly expanding, and annual quality reports are issued. Several important scientific studies are based on DMD data.
DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment and research.
Objectives
The incidence of actinic keratosis (AK) is increasing, and several treatment options are available. The aim of this study was to describe clinical characteristics and treatment patterns in ...patients with AK treated by Danish dermatologists.
Methods
A multicenter, non‐interventional, cross‐sectional study was conducted. Three dermatology hospital departments and seven private dermatology clinics enrolled eligible AK patients consecutively during one week.
Results
A total of 312 patients were included. Non‐melanoma skin cancer (NMSC) was previously reported in 51.0% of patients and currently suspected in 9.4% of AK‐affected anatomical regions. Lesions of AK were located primarily on the face (38.6%), scalp (12.8%), and hands (11.2%). Actinic keratosis commonly presented with multiple AK lesions (38.6%) and field cancerization (38.5%). The treatments used most frequently were cryotherapy (57.7%) and photodynamic therapy (PDT) with methyl aminolevulinate (17.1%) and imiquimod (11.2%). The likelihood of receiving cryotherapy was higher for men (odds ratio OR 1.65, 95% confidence interval CI 1.10–2.47) and increased with age (2.2% per year, 0.4–4.0%). PDT represented the most frequently applied treatment for severe actinic damage and was more likely to be prescribed to women (OR 4.08, 95% CI 2.22–7.47) and young patients (OR 0.97 per year, 95% CI 0.95–0.99). The prevalence of severe actinic damage (17.3% versus 9.6%) and intake of immunosuppressive medication (29.0 versus 2.0) were higher among hospital patients compared with those treated in private practices (P < 0.0001).
Conclusions
The majority of AK patients in Danish dermatology clinics have a history of skin cancer, and NMSC is suspected in almost 10% of AK‐affected regions. Cryotherapy is the most frequently used treatment overall, except in instances of severe actinic damage, in which PDT is the first‐choice treatment.
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