NITROSOGENESIS OF CUTANEOUS MELANOMA: SIMULTANEOUSLY DEVELOPMENT OF PRIMARY CUTANEOUS THICK MELANOMA OF THE BREAST, THIN MELANOMA/DYSPLASTIC MOLE OF THE BACK DURING PARALLEL INTAKE OF BISOPROLOL, AMLODIPINE AND VALSARTAN/ HCT: NITROSAMINE POLYCONTAMINATION IN THE MULTIMEDICATION AS THE MOST POWERFUL SKIN CANCER TRIGGER.

According to the latest and modern concepts- polymorbidity and polymedication are perceived as one of the most likely triggers for the development and progression of skin cancer (and melanomas in particular). The reason for this should be sought in polycontamination with nitrosamines (in the context of polymorbidity and polymedication of affected patients). This polycontamination is expanding in scale with each passing day and this in turn allows its detailed (albeit postponed) analysis. The concept of polycontamination could be related on the one hand to: 1) the patient's medication (number of drugs affected by nitrosamine contamination), but also to: 2) the number of mutagens or so-called contaminants (nitrosamines) contained in a single drug preparation. Unfortunately, the recently introduced acceptable daily intake dose (ADI) as a concept by the regulatory institutions, does not find its much desired application due to : 1) the lack of precise indication regarding the nitrosamine concentration on the leaflet of each potentially/actually contaminated medicine ; 2) the immediately resulting impossibility to calculate the daily acceptable dose (concentration of mutagens) in each patient (within the framework of polymedication), as well as 3) the ever increasing number/type of those identified in medicines as contaminants. Thus, in practice, the daily medication intake (of several drugs belonging to the groups of drugs declared as officially contaminated) could have adverse consequences for the health of patients precisely due to the fact that: the concentration of nitrosamines in each of the drugs taken could (not) exceed the аcceptable daily intake dose, but the total cumulative intake for the day would (most likely) be - many times higher. At present, however, this calculation turns out to be more of a ˝dream˝: A delusion or a myth about a personalized medical approach. On a pragmatic level, it could be concluded that: the establishment of certain stereotypes of clinical behaviour (such as the occurrence of melanomas, for example) after the intake of a heterogeneous class of drugs (which in all likelihood contain relatively similar carcinogens/nitrosamines in terms of composition and concentration), should suggest at least a common pathogenesis. The article focuses the attention of clinicians on the issues related to the coadministration of potentially nitrosamine-contaminated drugs for high blood pressure (such as Bisoprolol, Amlodipine and Valsartan/Hydrochlorothiazide), while also emphasizing the outcomes that could result from this long-term co-administration: simultaneous appearance of thick melanoma in the left breast area, thin melanoma on the back and dysplastic nevus thoracic on the left. The Nitrosogenesis of melanoma appears to be a ˝new perspective/beam of light˝ concerning its pathogenesis, and from a radically different angle of observation. The confirmatory nature of the clinical picture (multiple melanomas) in the patient we presented could be seen as confirmatory of a number of analogous cases of multiple melanomas occurring after intake of nitrosamine contaminated antihypertensive drugs. The feasibility of personalized single-stage melanoma surgery, which was applied to the patient presented, is emphasized. The choice of a surgical resection field of 1 cm for thin melanomas with a suspected (clinically/ dermoscopically) tumour thickness of less than 1 mm proved in practice to be an adequate approach, in accordance with the standards of the newly developed innovative guideline for one step surgical removal of cutaneous melanomas (OSMS).