Practical indications for the management of non-melanoma skin cancer patients

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), together encompassed in the term non-melanoma skin cancers (NMSC), are the most common cancers among fair-skinned populations. Individuating accurate risk stratification of NMSC patients is crucial to select different options among various treatment strategies. The majority of low risk NM SCs are easily treated with surgery, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (curettage, cautery and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). However, there is a subset of "high-risk" NM SC characterized by prognostic factors associated to aggressive behavior, such as tumor location and size, clinical margins, histopathological variants, recurrence or previous treatment. These lesions need to be treated accordingly also by mean of adjuvant treatments. The contribution of a multidisciplinary team is necessary to appropriately manage patients affected by advanced NM SC. The aim of these practical indications is to provide a useful guidance for risk stratification of NMSC patients in clinical setting and for consequential treatment choice, resulting in individualized management strategies

The behaviour of tributyl phosphate in an organic diluent

Tributyl phosphate (TBP) is used as a complexing agent in the Plutonium Uranium Extraction (PUREX) liquid-liquid phase extraction process for recovering uranium and plutonium from spent nuclear reactor fuel. Here, we address the molecular and microstructure of the organic phases involved in the extraction process, using molecular dynamics to show that when TBP is mixed with a paraffinic diluent, the TBP self-assembles into a bi-continuous phase. The underlying self-association of TBP is driven by intermolecular interaction between its polar groups, resulting in butyl moieties radiating out into the organic solvent. Simulation predicts a TBP diffusion constant that is anomalously low compared to what might normally be expected for its size; experimental nuclear magnetic resonance (NMR) studies also indicate an extremely low diffusion constant, consistent with a molecular aggregation model. Simulation of TBP at an oil/water interface shows the formation of a bilayer system at low TBP concentrations. At higher concentrations, a bulk bi-continuous structure is observed linking to this surface bilayer. We suggest that this structure may be intimately connected with the surprisingly rapid kinetics of the interfacial mass transport of uranium and plutonium from the aqueous to the organic phase in the PUREX process

Drug-induced hair colour changes

Hair colour modifications comprise lightening/graying, darkening, or even a complete hair colour change, which may involve the scalp and/or all body hair. Systemic medications may cause hair loss or hypertrichosis, while hair colour change is an uncommon adverse effect. The rapidly increasing use of new target therapies will make the observation of these side effects more frequent. A clear relationship between drug intake and hair colour modification may be difficult to demonstrate and the underlying mechanisms of hair changes are often unknown. To assess whether a side effect is determined by a specific drug, different algorithms or scores (e.g. Naranjo, Karch, Kramer, and Begaud) have been developed. The knowledge of previous similar reports on drug reactions is a key point of most algorithms, therefore all adverse events should be recognised and reported to the scientific community. Furthermore, even if hair colour change is not a life-threatening side effect, it is of deep concern for patient's quality of life and adherence to treatment. We performed a review of the literature on systemic drugs which may induce changes in hair colour

Molecular genetics of cutaneous squamous cell carcinoma: perspective for treatment strategies

Cutaneous squamous cell carcinoma (cSCC) represents 20% of all skin cancers. Although primary cSCCs can be successfully treated with surgery, a subset of highly aggressive lesions may progress to advanced disease, representing a public health care problem with significant cancer-related morbidity and mortality. A complex network of genes (TP53, CDKN2A, NOTCH1 and NOTCH2, EGFR and TERT) and molecular pathways (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) have been shown to play an important role in the pathogenesis of cSCC. The epigenetic regulation of TP53 and CDKN2A is an attractive therapeutic target for the treatment of cSCC, as well as NOTCH activating agents capable to restore its tumour-suppressor function. EGFR inhibitors including both monoclonal antibodies (cetuximab and panitumumab) and tyrosine kinase inhibitors (erlotinib, gefitinib and dasatinib) have been used in clinical trials for the treatment of advanced cSCC, achieving only partial clinical benefit. Recently, an immune-modulatory drug (cemiplimab) has been introduced for the treatment of advanced cSCC with good clinical results and a favourable safety profile, while other PD1/PD-L1 inhibitors, either as monotherapy or in combination with targeted therapies, are currently under investigation. This review focuses on molecular findings involved in the pathogenesis of cSCC and their implications for the future development of new treatment strategies. In addition, current and ongoing treatments on targeted therapies and/or immunotherapy are illustrated

Polymers of Intrinsic Microporosity Containing Tröger Base for CO₂ Capture

Properties of four polymers of intrinsic microporosity containing Tröger’s base units were assessed for CO₂ capture experimentally and computationally. Structural properties included average pore size, pore size distribution, surface area, and accessible pore volume, whereas thermodynamic properties focused on density, CO₂ sorption isotherms, and enthalpies of adsorption. It was found that the shape of the contortion site plays a more important role than the polymer density when assessing the capacity of the material, and that the presence of a Tröger base unit only slightly affects the amount adsorbed at low pressures, but it does not have any significant influence on the enthalpy of adsorption fingerprint. A comparison of the materials studied with those reported in the literature allowed us to propose a set of guidelines for the design of polymers for CO₂ capture applications

The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low >= G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team

Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple Melanomas and Association with MC1R Genotype: Findings from Molecular and Immunohistochemical Analysis

Data on somatic heterogeneity and germline\ue2\u80\u93somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600Edetection (\uce\uba = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test

Lentigo maligna and lentigo maligna melanoma in patients younger than 50 years old: A multicentric international clinical-dermoscopic study

Background: LM/LMM is usually diagnosed in elderly patients when it is a large lesion. However, it is important to detect it at an earlier stage to minimize the size of the surgical procedure. Objective: To determine the clinical, dermoscopic and confocal features of LM/LMM in patients &lt;50 years old. Method: This study included cases of consecutively excised LM/LMM arising in patients younger than 50 years if clinical and dermoscopic images were available; confocal images were considered when present. Multicenter study involving tertiary referral centers for skin cancer management. Consecutive patients younger than 50 years with a complete set of clinical and dermoscopic images and histopathological diagnosis of LM/LMM. The aim of this study to define clinical and dermoscopic features related to young age group such as size, dermoscopic criteria and when available, confocal features. Results: A total of 85 LM/LMM of the face from 85 patients younger than 50 years were included in the study. A regression model showed a direct association with the size of the lesion (R2 = 0.08, p-value = 0.01) and with the number of dermoscopic criteria at diagnosis (R2 = 0.12, p-value &lt; 0.01). In a multi variable analysis an increasing number of dermoscopic criteria was correlated with increased age of the patients (p-value &lt; 0.01), while the presence of grey color was a predictor of a younger age at diagnosis (p-value = 0.03). RCM revealed the presence of melanoma diagnostic criteria in all cases (pagetoid cells and atypical nesting). Conclusions: LM is not a disease limited to the elderly as previously thought. LM presenting in young adults tends to be smaller and with fewer dermoscopic criteria making its diagnosis challenging. Careful evaluation of facial pigmented lesions prior to cosmetic procedures is mandatory to avoid incorrectly treating early LM as a benign lesion