Cutaneous melanoma metastases: Clinical and dermoscopic findings.

BACKGROUND: About 2%-20% of melanoma patients will develop cutaneous melanoma metastases (CMM). Their clinical diagnosis still remains challenging because of the variation of clinical and dermoscopic characteristics. Until today, few studies exist concerning the dermoscopic image of CMM but no one has focused on its possible association with clinicopathological melanoma characteristics. METHODS: Between 2002 and 2019, 42 patients diagnosed with melanoma at Andreas Syggros Hospital developed CMM. We studied the dermoscopic presentation of these metastases and its possible association with the clinical and histologic characteristics of the underlying melanoma. RESULTS: There were 20 male and 22 female patients with a mean age of 64.02 years. Nineteen patients developed satellites and 23 in transit metastases. Mean Breslow index was estimated at 2.93 mm and ulceration was observed in half of the tumours (50%). Almost half of the patients developed cutaneous metastases on the lower limbs (45.24%). We identified 5 dermoscopic patterns of CMM: saccular, amelanotic, homogenous, vascular and polymorphic. Homogenous (30.95%) and amelanotic (28.57%) were the most common patterns. Homogenous pattern was the most common in satellite metastases while amelanotic was mostly observed in in-transit metastases. Homogenous pattern was more frequent among superficial spreading melanomas. Patients with thin (<1 mm) and medium depth (1-2 mm) melanomas mostly developed metastases with saccular pattern. Vascular pattern was only present in metastases of tumours with Breslow index 2-4 mm. Homogenous and amelanotic were the only patterns found in tumours with Breslow index >4 mm. CONCLUSIONS: We observed that vascular structures were more frequent in metastases of deeper tumours while nevus-like structures were more common in metastases of thinner tumours. CMM occasionally may constitute the first clinical sign of melanoma disease. Therefore, it is important for clinicians to recognize their dermoscopic patterns which seem to be associated with some of the clinical and histological characteristics of cutaneous melanomas.

Atypical presentation of cutaneous angiosarcoma: review of the literature.

Cutaneous angiosarcoma (CAS) is an aggressive tumour of vascular or lymphatic origin. Although relatively rare, it needs to be recognized and treated early. CAS typically arises on the head or neck as a bruise or raised purplish-red papule or plaque. However, it can sometimes resemble a benign skin lesion, leading to delay in diagnosis and consequent poor patient outcome. CAS may be mistaken for inflammatory, autoimmune or infectious disease, or for a benign skin tumour or post-traumatic lesion. We analyse the atypical clinical forms of this aggressive tumour and review the literature.

Surgical Treatment and Recurrence of Cutaneous Nasal Malignancies: A 26-Year Retrospective Review of 1795 Patients.

Frequent localization of facial malignancies in the nasal area and their required complete surgical extirpation pose a significant challenge to the plastic surgeon, who is called to perform a suitable delicate reconstruction of produced nasal skin defects. The present study was aimed to examine the role of tumor characteristics in the prognosis of patients with nasal skin cancer undergoing surgical management.A retrospective review of 1795 patients operated on for nasal cutaneous neoplasms during a 26-year period is presented in our study. Descriptive statistics were appropriately calculated; multivariate Cox regression analysis was performed regarding the possible risk factors for recurrence. Only those with a complete follow-up were included in the study. The mean age of our study population was 66.7 years with a male majority (52.4%). Basal cell carcinoma appeared as the most common histological type (87.7%), followed by squamous cell carcinoma (7.9%); the latter correlated with poor prognosis.The nasal sidewalls were the most frequent lesion location (29.8%), followed by the alae (27.8%), dorsum (21.7%), and tip (19.3%). The columella was very rarely affected (0.5%) but was associated with increased recurrence [hazard ratio, 4.74; 95% confidence interval (CI), 1.12-20.00; P = 0.034]. Most patients were treated with elliptical excision and direct closure (58.7%). Local flaps (31.0%) and skin grafting (9.0%) proved very reliable surgical options, especially for larger, high-risk lesions. Recurrence transpired in 46 patients (2.6%) and 4 skin cancer-related deaths occurred.Surgical modality of choice should be individualized and carefully adjusted to patients' needs. Moreover, more elective techniques, such as Mohs micrographic surgery or cumulative therapeutic approaches, like irradiation, should be examined as a beneficial aid to confront high-risk malignancies.

High-frequency p16(INK) (4A) promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma.

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16(INK) (4A) promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation-specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki-67 index), p16(INK) (4A) and SETDB1 expression were evaluated by immunohistochemistry. High-frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16(INK) (4A) promoter methylation was higher in vertical growth-phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16(INK) (4A) methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1-30%) p16(INK) (4A) expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16(INK) (4A) methylation and p16(INK) (4A) expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0-5/mm(2) vs >5/mm(2) , P = 0.0869), advanced Clark level (III-V, P = 0.0380), epidermal involvement (P = 0.0331) and the non-chronic sun exposure-associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16(INK) (4A) promoter and several prognostic parameters in melanomas.

Hyalurosome gene regulation and dose-dependent restoration of skin atrophy by retinaldehyde and defined-size hyaluronate fragments in dermatoporosis.

BACKGROUND: Dermatoporosis is an emerging clinical condition caused by chronological skin aging, long-term sun exposure and chronic use of corticosteroids; however, genomic expression in dermatoporosis and the efficacy of different therapeutic approaches to prevent and treat dermatoporosis have not been investigated so far. OBJECTIVE: We examined the possible effect of topical retinaldehyde (RAL) and defined-size hyaluronate fragments (HAFi) on the expression of hyalurosome genes potentially involved in the pathogenesis of dermatoporosis. We also explored the effect of different concentrations of HAFi on skin thickness. METHODS: 13 persons were separated into a young control group (n = 8) and a dermatoporosis group (n = 5). Topical treatment of both groups with a combination of 0.05% RAL and 1 or 0.2% HAFi was applied on the forearm twice daily for 30 days. Forearm skin biopsies of both groups were performed before and after application. Hyalurosome genes CD44, heparin-binding epidermal growth factor (HB-EGF), ErbB1, hyaluronate synthase 3 (HAS3) and Hyal2 were chosen as potential markers of dermatoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for quantification of mRNA expression of the target hyalurosome genes. Measurement of forearm skin thickness before and after treatment was performed by ultrasonography. Analysis of the results was done by Student's t test. A p value <0.05 was considered statistically significant. RESULTS: In qRT-PCR analysis the relative expression of hyalurosome (CD44, HAS3, HB-EGF) genes was found to be reduced in patients prior to topical treatment and to be notably increased following treatment. The reduced expression of CD44 and HAS3 in patients was specifically restored in dermatoporotic patients after treatment. No difference in skin thickness was observed in controls after treatment. The treatment caused a significant increase in skin thickness in dermatoporotic patients. This increase was more significant with 1% HAFi when compared to 0.2% HAFi. RAL and HAFi also caused a significant reduction in purpuric lesions in patients with dermatoporosis. CONCLUSION: Our results indicate that topically applied RAL and HAFi regulate hyalurosome gene expression in dermatoporosis and that they show a dose-dependent effect on the correction of skin atrophy in dermatoporotic patients.

Simultaneous melanomas in the setting of multiple primary melanomas.

It is estimated that about 1-13% of melanoma patients will develop multiple primary melanomas. Although the occurrence of subsequent tumors has been described during the last few years, the development of simultaneous melanomas has not yet been extensively studied. We reviewed our registries to identify patients with multiple primary melanomas. We studied epidemiological, clinical, and histological characteristics of patients who were diagnosed with simultaneous melanomas and compared them with those of patients who developed non-synchronous multiple primary melanomas. As simultaneous were defined subsequent melanomas that were diagnosed either at the same visit or within a time-period of maximum of 1 month. Between 2000 and 2020, 2500 patients were diagnosed with melanoma at Andreas Syggros Hospital. 86 (3.4%) patients presented multiple primary melanomas and among them, 35 (40.7%) developed simultaneous melanomas. Patients with simultaneous melanomas developed more frequently more than 2 tumors. First tumors of patients with non-synchronous melanomas were significantly thicker than second tumors while those of patients with simultaneous melanomas did not differ significantly. Slight differences in the tumor localization, staging and histologic type were observed between the two groups. However significant differences were ascertained between first and second tumors in both groups. Simultaneous melanomas occupy an important proportion of multiple primary melanomas, affecting a non-negligible number of patients. Slight differences between simultaneous and non-synchronous multiple primary melanomas seem to define a distinct subcategory of multiple primary melanomas.

In Vivo Evaluation of Wound Healing Efficacy of Gel-Based Dressings Loaded with Pycnogenol™ and Ceratothoa oestroides Extracts.

Ceratothoa oestroides and French maritime pine bark (Pycnogenol™) extracts are considered promising therapeutic agents in wound healing. This study explores the healing efficacy of composite dressings containing these extracts, aiming to enhance their stability and effectiveness, utilizing a low-temperature vacuum method for producing Sodium Alginate-Maltodextrin gel dressings. Surgical wounds were inflicted on SKH-hr2 hairless mice. Dressings were loaded with Pycnogenol™ and/or C. oestroides extracts and assessed for their efficacy. Wound healing was primarily evaluated by clinical and histopathological evaluation and secondarily by Antera 3D camera and biophysical measurements. Dressings were stable and did not compromise the therapeutic properties of C. oestroides extract. All interventions were compared to the C. oestroides ointment as a reference product. Most of the wounds treated with the reference formulation and the C. oestrodes dressing had already closed by the 15th day, with histological scores of 7 and 6.5, respectively. In contrast, wounds treated with Pycnogenol™, either alone or in combination with C. oestroides, did not close by the end of the experiment (16th day), with histological scores reaching 15 in both cases. Furthermore, treatment with 5% Pycnogenol™ dressing appeared to induce skin thickening and increase body temperature. The study underscores the wound healing potential of C. oestroides extracts and highlights the need for further research to optimize Pycnogenol™ dosing in topical applications.

Differential biofilm formation and chemical disinfection resistance of sessile cells of Listeria monocytogenes strains under monospecies and dual-species (with Salmonella enterica) conditions.

This study aimed to investigate the possible influence of bacterial intra- and interspecies interactions on the ability of Listeria monocytogenes and Salmonella enterica to develop mixed-culture biofilms on an abiotic substratum, as well as on the subsequent resistance of sessile cells to chemical disinfection. Initially, three strains from each species were selected and left to attach and form biofilms on stainless steel (SS) coupons incubated at 15°C for 144 h, in periodically renewable tryptone soy broth (TSB), under either monoculture or mixed-culture (mono-/dual-species) conditions. Following biofilm formation, mixed-culture sessile communities were subjected to 6-min disinfection treatments with (i) benzalkonium chloride (50 ppm), (ii) sodium hypochlorite (10 ppm), (iii) peracetic acid (10 ppm), and (iv) a mixture of hydrogen peroxide (5 ppm) and peracetic acid (5 ppm). Results revealed that both species reached similar biofilm counts (ca. 10(5) CFU cm(-2)) and that, in general, interspecies interactions did not have any significant effect either on the biofilm-forming ability (as this was assessed by agar plating enumeration of the mechanically detached biofilm bacteria) or on the antimicrobial resistance of each individual species. Interestingly, pulsed-field gel electrophoresis (PFGE) analysis clearly showed that the three L. monocytogenes strains did not contribute at the same level either to the formation of mixed-culture sessile communities (mono-/dual species) or to their antimicrobial recalcitrance. Additionally, the simultaneous existence inside the biofilm structure of S. enterica cells seemed to influence the occurrence and resistance pattern of L. monocytogenes strains. In sum, this study highlights the impact of microbial interactions taking place inside a mixed-culture sessile community on both its population dynamics and disinfection resistance.

Serum leptin, adiponectin and tumor necrosis factor-α in hyperlipidemic rats with/without concomitant diabetes mellitus.

We compared the lipid profiles and serum levels of leptin, adiponectin and tumor necrosis factor-α (TNF-α) in rats with/without hyperlipidemia and with/without concomitant diabetes mellitus. Forty 10-wk-old male Wistar rats were divided into four groups. Groups A and C received standard food for 12 wks. Groups B and D received a high-fat diet enriched with 2% additional cholesterol. Moreover, insulin-deficient (type I) diabetes mellitus was induced in rats in groups C and D with intraperitoneal injections of streptozotocin. Fasting serum leptin levels were decreased in diabetic groups (groups C and D) compared with controls. Fasting serum adiponectin levels were decreased in groups C and D compared with group A. Serum TNF-α levels were augmented in groups B and D, those fed with an atherogenic diet. By contrast, TNF-α levels were decreased in group C. Our data suggest that serum leptin, adiponectin and TNF-α levels may serve as markers of obesity and type I diabetes mellitus.

Combined effect of MAP and thyme essential oil on the microbiological, chemical and sensory attributes of organically aquacultured sea bass (Dicentrarchus labrax) fillets.

The present study evaluated the combined effect of Modified Atmosphere Packaging (MAP) using two different gas mixtures (40% CO2/50% N2/10% O2; treatment M1, 60% CO2/30% N2/10% O2, treatment M2), and thyme oil (0.2% v/w, T) used as a natural preservative, on the quality and shelf life extension of fresh filleted sea bass, product of organic aquaculture, during refrigerated storage (4 +/- 0.5 degrees C), for a period of 21 days. Aerobically packaged sea bass fillets (A) were used as control samples. The dominant bacteria in the microflora of sea bass fillets, irrespective of treatment, were the pseudomonads and the H2S-producing bacteria while lactic acid bacteria were also part of the dominant microflora. Total viable counts for fresh sea bass fillets stored aerobically exceeded 7 log CFU/g after 7 days, while treatments A+T, M1, M2 and M2+T reached the same value on days 9, 10, 12 and 19, respectively. Among the chemical indices determined, TBA values were within the good quality limits (2-4 mg MDA/kg), during the sensory shelf lives of sea bass samples, irrespective of treatment. TVB-N proved to be a suitable index for the spoilage of sea bass fillets stored at 4 degrees C. Samples A and A+T, M1, M2, M2+T exceeded the proposed upper TVB-N acceptability limit (10 mg N/100 g) on days 6, 8, 9, 13 and 17 of storage respectively. TMA-N values of the samples A, A+T and M1, M2, M2+T exceeded the proposed limit (4 mg N/100 g) on days 6, 9, 9-10, 13 and 19 of storage, respectively, and correlated well with the microbiological data, indicating that along with TVB-N, TMA-N may serve as a useful index for sea bass fillets spoilage. As regards sensory evaluation, the presence of thyme oil proved to improve the sensory quality of sea bass fillets when used in combination with MAP2, providing a shelf life of 17 days as compared to 6 days of the control samples.

Crossmodal binding rivalry: A "race" for integration between unequal sensory inputs.

Exposure to multiple but unequal (in number) sensory inputs often leads to illusory percepts, which may be the product of a conflict between those inputs. To test this conflict, we utilized the classic sound induced visual fission and fusion illusions under various temporal configurations and timing presentations. This conflict between unequal numbers of sensory inputs (i.e., crossmodal binding rivalry) depends on the binding of the first audiovisual pair and its temporal proximity to the upcoming unisensory stimulus. We, therefore, expected that tight coupling of the first audiovisual pair would lead to higher rivalry with the upcoming unisensory stimulus and, thus, weaker illusory percepts. Loose coupling, on the other hand, would lead to lower rivalry and higher illusory percepts. Our data showed the emergence of two different participant groups, those with low discrimination performance and strong illusion reports (particularly for fusion) and those with the exact opposite pattern, thus extending previous findings on the effect of visual acuity in the strength of the illusion. Most importantly, our data revealed differential illusory strength across different temporal configurations for the fission illusion, while for the fusion illusion these effects were only noted for the largest stimulus onset asynchronies tested. These findings support that the optimal integration theory for the double flash illusion should be expanded so as to also take into account the multisensory temporal interactions of the stimuli presented (i.e., temporal sequence and configuration).

Metastatic liver disease and fulminant hepatic failure: presentation of a case and review of the literature.

Although liver metastases are commonly found in cancer patients, fulminant hepatic failure (FHF) secondary to diffuse liver infiltration is rare. Furthermore, clinical presentation and laboratory findings are obscure and far from being pathognomonic for the disease. We report a case of a patient who died in the intensive care unit of our hospital from multiple organ failure syndrome secondary to FHF, as a result of liver infiltration from poorly differentiated small cell lung carcinoma. We also present the current knowledge about the clinical picture, laboratory findings and physical history of neoplastic liver-metastasis-induced FHF.

Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid cancer: is there an association? A case report and literature review.

Type 1 diabetes mellitus (T1DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency. Associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, can coexist in patients with T1DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase (anti-tTG-IgA), thyroglobulin, and thyroid peroxidase (anti-TG, anti-TPO), as well as antibodies against gastric parietal cells. Children with T1DM may also develop organ-specific multiple autoimmunity, with the coexistence of one or more autoimmune disorders. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. We present a child with T1DM and multiple autoimmunity including autoimmune Hashimoto's thyroiditis (HT), who developed thyroid cancer. The literature on the prevalence of associated autoimmunity in children with T1DM and the prevalence, pathogenesis, and timely diagnosis of thyroid cancer among patients with HT is also reviewed.

Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 at the early stages of atherosclerosis in a rat model.

BACKGROUND: Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM-1), participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherosclerosis. The aim of the study was to examine the expression of VCAM-1 and ICAM-1 in the aorta of rats at the early stages of atherosclerosis and the correlation with their plasma concentrations. MATERIALS AND METHODS: Male rats (n=44), 10 weeks of age, were divided in 4 groups. Groups A and C (n=12) were fed with rich cholesterol diet for 12 and 16 weeks, respectively. Group B (regression group, n=12) was fed for the first 12 weeks with rich cholesterol diet and for another 4 weeks with normal diet. Group D (control group, n=8) was fed with normal diet for 12 weeks. We measured the serum lipid profile, the concentration of soluble ICAM-1 and the immunohistochemical expression of ICAM-1 and VCAM-1 in the endothelium, media and vasa vasorum of the aorta. RESULTS: There were significant differences (p<0.05) in the expression of ICAM-1 between group C (maximum time of rich cholesterol diet) and all other groups in the 3 groups of the aorta studied. There was regression of the expression of ICAM-1 in group B and significant differences (p<0.05) between group B and all the other groups, except group D in the expression of ICAM-1. There were no significant differences in the expression of VCAM-1 between any groups. The serum concentration of soluble ICAM-1 positively correlated with the expression of the molecule in the vasa vasorum (r=0.35, p<0.05) and fibroblasts/smooth muscular cells (r=0.34, p<0.05) of the aorta. CONCLUSION: A cholesterol diet plays a role in the expression of ICAM-1 but not in that of VCAM-1 in the rat aorta. The expression of ICAM-1 in the aorta regresses after the withdrawal of a cholesterol-rich diet. Soluble ICAM-1 is a reliable measure of ICAM-1 expression in the aorta, vasa vasorum and fibroblasts/smooth muscle cells.

Refractory iron-deficiency anaemia due to silent Helicobacter pylori gastritis in children.

UNLABELLED: We describe the cases of three children with chronic active Helicobacter pylori gastritis and iron-deficiency anaemia without evidence of oesophagogastrointestinal bleeding. In all cases, long-standing iron supplementation became effective only after eradication of Helicobacter pylori. CONCLUSION: Iron-deficiency anaemia may be due to clinically inapparent H. pylori gastritis.