Cheek аdvancement flap for BCC of the nose: the nitrosamine contamination during the combined drug intake as important skin cancer triggering factor

Abstract

The emerging insights and (hypo)theses regarding the pathogenesis of skin cancer are particularly intriguing, as they introduce a novel and unconventional etiopathogenetic factor: the presence of contaminants, specifically nitrosamines, in medications for high blood pressure, diabetes mellitus and many others. The combined use of potentially or actually contaminated preparations creates conditions for the simultaneous intake of multiple carcinogens, some of which possess both genotoxic and phototoxic properties.
The authorisation regimes for the availability, but also for the daily, prolonged, ”officially undisclosed” intake of nitrosamines heterogeneous in type and carcinogenicity in medicines are based on: the determination of their carcinogenic potency based on a specific test in: 1) bacteria/Ames Test and/or the search for an analogue of carcinogenicity in 2) rodents/CPCA Test. However, the interpretations of the results of these tests should in no way be regarded as reciprocal in humans. The processes of ʺʺ human carcinogenesisʺ  are dynamic and multifactorial and could not be characterized by interpretation or equivalence of results from ʺstatic testsʺ conducted in bacteria and/or rodents. Moreover, these tests do not analyse the concurrent intake or simultaneous action of several carcinogens (referring here specifically to the polycontamination of polymedication) on a given, be it unicellular, multicellular, rodents or even human organism. In practice, these tests paraphrase or reinforce carcinogenic availability in drugs as being alternativeless, but remaining at the same time classified for the medical personnel and the final users. We describe a 74-year-old male with arterial hypertension and diabetes, undergoing systemic therapy with losartan/hydrochlorothiazide, nifedipine, moxonidine, metoprolol, glimepiride and metformin, who subsequently developed 18 cutaneous cancers – 2 basal and 16 squamous carcinomas – over a 5-year period. The article also discusses the treatment of the last cutaneous tumor located on the left nasal sidewall, successfully managed using a cheek advancement flap. It further explores the role of drug-mediated Nitrosogenesis and Photo-Nitroso-Carcinogenesis. The broad base of the pyramid of drug-mediated carcinogenesis/nitrosogenesis underlying skin cancer pathogenesis could be conditioned by: 1) the presence of phototoxic but at the same time 2) genotoxic substances, also known for decades as nitrosamines. Regardless of the class of drugs in which these mutagens and (to some extent) photocarcinogens are found (antidiabetic, antihypertensive or antiarrhythmic drugs, but also a number of others), their pro-carcinogenic action in all likelihood appears to be pathogenetically associated/related to the generation of the same tumors: keratinocytic. Whether the nitrosamines are the only substances in the drugs determining the phototoxicity, genotoxicity and subsequent photocarcinogenicity remains hanging in the scientific space with full force, but also with a decreasing amount of doubt.