MELANOMA AND DYSPLASTIC NEVI DEVELOPMENT AFTER RANITIDINE/ RILMENIDINE/МOXONIDINE, LERCANIDIPINE, ROSUVASTATIN AND VERAPAMIL/ TRANDOLAPRIL- NEW DATA/CASE SERIES. THE POTENTIAL ROLE OF NITROSAMINE/ NDSRIS CONTAMINATION IN POLYMEDICATION AS SUBSTANTIAL SKIN CANCER TRIGGERING FACTOR

Abstract

The idea of drug-induced/exogenic Nitrosogenesis is driven by
the possibility of prolonged exposure of the human body to the
influence of nitrosamines within the drug intake – substances
or contaminants that have been proven to be carcinogenic or
mutagenic one.
Until recently, there was a complete lack of data in the scientific
literature on the relationship between cancer, polymedication
and polycontamination with nitrosamines.
In the last decade, melanoma has been described repeatedly in
the medical literature as a possible side-effect within the intake
of possibly with nitrosamines contaminated medications such
as: Valsartan, Hydrochlorothiazide, Amlodipine, Nebivolol,
Bisoprolol and Perindopril.
However, the contribution of the currently presented new
data (5 new patients) is also due to the establishment of the
possible pathogenetic role (with respect to melanoma) of
several completely new drugs, previously unknown to the
scientific community (potentially/actually contaminated with
carcinogens/nitrosamines), such as: Ranitidine, Rosuvastatin,
Lercanidipine, Rilmenidine, Trandolapril, Moxonidine and
Verapamil.
The leading and connecting link in shared new and old drug
combinations of heterogeneous drug classes (polymedication)
and melanoma development and progression remains again one
and the same : the possible availability of nitroso component in
the frame of exogenous nitrosogenesis according to the official
FDA lists of 2023.
The number of drugs shared as contaminated with nitrosamines
after whose intake melanomas occur is increasing.
Nitrosogenesis remains a new beginning, a new understanding
and new interpretation of the carcinogenesis concerning
melanoma, but probably also of cancer in general. Its further
elucidation looks more than promising and is yet to come.
More than worrying at the moment remains the fact that the
scientific community has to clarify if : 1) peak concentrations
of nitrosamines or NDSRIs within the framework of
monomedication or 2) normal concentrations within the
polymedication (catalogued in the list of FDA/ 2023 as
potentially contaminated with hypothetical carcinogens), could
hide relatively short-term risk of the development of real tumors:
cutaneous melanomas and/or their precursor lesions.
The validation of the concept of Nitrosogenesis and its
relationship to Сarcinogenesis, is achieved in practice on the basis of the following facts: that it is the occurrence of the same
monomorphic clinical pattern (melanoma/dysplastic nevi) ,
developing after the intake of drugs with different mechanism of
action, contaminated with nitrosamines / NDSRIs. The unifying
link between the intake of certain drugs and the development
of certain tumours remains the presence of nitrosamines.
Ingredients that are present in drug preparations, identified as
availability and as carcinogenic potency, but not yet reflected in
packaging or prescriptions. The question remains: why?

Full text

EORGIAN
EDICAL
EWS
ЕЖЕМЕСЯЧНЫЙ НАУЧНЫЙ ЖУРНАЛ
Медицинские новости Грузии
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No 1 (322) Январь 2022
ISSN 1512-0112
ТБИЛИСИ - NEW YORK
NO 11 (344) ноябрь 2023

GMN: Georgian Medical News is peer-reviewed, published monthly journal committed to promoting
the science and art of medicine and the betterment of public health, published by the GMN Editorial
Board and The International Academy of Sciences, Education, Industry and Arts (U.S.A.) since
1994. GMN carries original scientic articles on medicine, biology and pharmacy, which are of
experimental, theoretical and practical character; publishes original research, reviews, commentaries,
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full text content is available through EBSCO databases.
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xelmisawvdomia EBSCO-s monacemTa bazebidan.
GMN: Georgian Medical News is peer-reviewed, published monthly journal committed to promoting
the science and art of medicine and the betterment of public health, published by the GMN Editorial
Board since 1994. GMN carries original scientic articles on medicine, biology and pharmacy, which
are of experimental, theoretical and practical character; publishes original research, reviews, commen-
taries, editorials, essays, medical news, and correspondence in English and Russian.
GMN is indexed in MEDLINE, SCOPUS, PubMed and VINITI Russian Academy of Sciences. The full
text content is available through EBSCO databases.
GEORGIAN MEDICAL NEWS
GMN: Медицинские новости Грузии - ежемесячный рецензируемый научный журнал, издаётся
Редакционной коллегией с 1994 года на русском и английском языках в целях поддержки
медицинской науки и улучшения здравоохранения. В журнале публикуются оригинальные
научные статьи в области медицины, биологии и фармации, статьи обзорного характера, научные
сообщения, новости медицины и здравоохранения. Журнал индексируется в MEDLINE, отражён
в базе данных SCOPUS, PubMed и ВИНИТИ РАН. Полнотекстовые статьи журнала доступны
через БД EBSCO.
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formats of the Agency of Medical Information of the Georgian Association of Business Press.
Published since 1994. Distributed in NIS, EU and USA.
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www.geomednews.com

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avtorTa sayuradRebod!
redaqciaSi statiis warmodgenisas saWiroa davicvaT Semdegi wesebi:
1. statia unda warmoadginoT 2 calad, rusul an inglisur enebze, dabeWdili
standartuli furclis 1 gverdze, 3 sm siganis marcxena velisa da striqonebs
Soris 1,5 intervalis dacviT. gamoyenebuli kompiuteruli Srifti rusul da ing-
lisurenovan teqstebSi - Times New Roman ( Кириллица), xolo qarTulenovan teqstSi
saWiroa gamoviyenoT AcadNusx. Sriftis zoma – 12. statias Tan unda axldes CD
statiiT.
2. statiis moculoba ar unda Seadgendes 10 gverdze naklebs da 20 gverdze mets
literaturis siis da reziumeebis (inglisur, rusul da qarTul enebze) CaTvliT.
3. statiaSi saWiroa gaSuqdes: sakiTxis aqtualoba; kvlevis mizani; sakvlevi
masala da gamoyenebuli meTodebi; miRebuli Sedegebi da maTi gansja. eqsperimen-
tuli xasiaTis statiebis warmodgenisas avtorebma unda miuTiTon saeqsperimento
cxovelebis saxeoba da raodenoba; gautkivarebisa da daZinebis meTodebi (mwvave
cdebis pirobebSi).
4. statias Tan unda axldes reziume inglisur, rusul da qarTul enebze
aranakleb naxevari gverdis moculobisa (saTauris, avtorebis, dawesebulebis
miTiTebiT da unda Seicavdes Semdeg ganyofilebebs: mizani, masala da meTodebi,
Sedegebi da daskvnebi; teqstualuri nawili ar unda iyos 15 striqonze naklebi)
da sakvanZo sityvebis CamonaTvali (key words).
5. cxrilebi saWiroa warmoadginoT nabeWdi saxiT. yvela cifruli, Sema-
jamebeli da procentuli monacemebi unda Seesabamebodes teqstSi moyvanils.
6. fotosuraTebi unda iyos kontrastuli; suraTebi, naxazebi, diagramebi
- dasaTaurebuli, danomrili da saTanado adgilas Casmuli. rentgenogramebis
fotoaslebi warmoadgineT pozitiuri gamosaxulebiT ti formatSi. mikrofoto-
suraTebis warwerebSi saWiroa miuTiToT okularis an obieqtivis saSualebiT
gadidebis xarisxi, anaTalebis SeRebvis an impregnaciis meTodi da aRniSnoT su-
raTis zeda da qveda nawilebi.
7. samamulo avtorebis gvarebi statiaSi aRiniSneba inicialebis TandarTviT,
ucxourisa – ucxouri transkripciiT.
8. statias Tan unda axldes avtoris mier gamoyenebuli samamulo da ucxo-
uri Sromebis bibliografiuli sia (bolo 5-8 wlis siRrmiT). anbanuri wyobiT
warmodgenil bibliografiul siaSi miuTiTeT jer samamulo, Semdeg ucxoeli
avtorebi (gvari, inicialebi, statiis saTauri, Jurnalis dasaxeleba, gamocemis
adgili, weli, Jurnalis #, pirveli da bolo gverdebi). monografiis SemTxvevaSi
miuTiTeT gamocemis weli, adgili da gverdebis saerTo raodenoba. teqstSi
kvadratul fCxilebSi unda miuTiToT avtoris Sesabamisi N literaturis siis
mixedviT. mizanSewonilia, rom citirebuli wyaroebis umetesi nawili iyos 5-6
wlis siRrmis.
9. statias Tan unda axldes: a) dawesebulebis an samecniero xelmZRvane-
lis wardgineba, damowmebuli xelmoweriTa da beWdiT; b) dargis specialistis
damowmebuli recenzia, romelSic miTiTebuli iqneba sakiTxis aqtualoba, masalis
sakmaoba, meTodis sandooba, Sedegebis samecniero-praqtikuli mniSvneloba.
10. statiis bolos saWiroa yvela avtoris xelmowera, romelTa raodenoba
ar unda aRematebodes 5-s.
11. redaqcia itovebs uflebas Seasworos statia. teqstze muSaoba da Se-
jereba xdeba saavtoro originalis mixedviT.
12. dauSvebelia redaqciaSi iseTi statiis wardgena, romelic dasabeWdad
wardgenili iyo sxva redaqciaSi an gamoqveynebuli iyo sxva gamocemebSi.
aRniSnuli wesebis darRvevis SemTxvevaSi statiebi ar ganixileba.

GEORGIAN MEDICAL NEWS
No 11 (344) 2023
Stepanyan Lusine, Papoyan Varduhi, Galstyan Alina, Sargsyan Diana.
THE PROBLEM OF COMPETENCIES MODELING IN THE SOCIAL-PSYCHOLOGICAL CRISIS CONDITIONS…….......……………6-12
Biduchak A, Mararash H, Mohammad Wathek O Alsalama, Chornenka Zh, Yasinska E.
ORGANIZATIONAL AND FUNCTIONAL MODEL OF IMPROVEMENT OF THE SYSTEM OF PREVENTION OF CONFLICT
SITUATIONS IN THE FIELD OF HEALTHCARE…………………………………………………..................................................………..13-18
Shalabh Kumar, Sanjay Kumar Yadav, Komal Patel, Renuka Jyothi. R, Bhupendra Kumar, Vikram Patidar.
EARLY IMPLANT OUTCOMES IN ADULTS WITH DENTAL DECAY TREATED WITH PHOTODYNAMIC TREATMENT…..……19-26
M. Zubiashvili, N. Kakauridze, P. Machavariani, T. Zubiashvili.
THE SIGNIFICANCE OF CIRCULATING SURFACTANT PROTEIN D(SP-D) AND DYSLIPIDEMIA IN CHRONIC OBSTRUCTIVE
PULMONARY DISEASE (COPD), CORONARY HEART DISEASE (CHD) AND THEIR COMBINATION……………....……………..27-33
Mohamed Hamdi Mohamed Elgawadi, Yasser Abdel Fattah Radwan, Sherif Abdel Latif Othman, Ahmed Samir Barakat, Ahmed Omar Sabry,
Abdallu Mohamed Ahmed.
RANDOMIZED COMPARATIVE STUDY OF DEFINITIVE EXTERNAL FIXATION VERSUS ORIF IN PILON FRACTURES: AN
EARLY CLINICAL OUTCOME REPORT…………………………………….....................................................……………………………34-38
Salome Glonti, Megi Inaishvili, Irina Nakashidze.
EVALUATION OF SOME LABORATORY PARAMETERS IN PATIENTS WITH MORBID OBESITY AFTER BARIATRIC
SURGERY……………………………………………………………………………………..............................……………………………..39-42
Balbeer Singh, Soubhagya Mishra, Rajnish Kumar, Devanshu J. Patel, Malathi.H, Bhupendra Kumar.
IMPLICATION OF THREAT FACTORS AND PREEXISTING DISORDERS IN DIFFERENT ISCHEMIC STROKE SUBGROUPS IN
ELDERLY PEOPLE: A SYSTEMATIC STUDY………………………………………….....................................................…………………43-46
Liubov Bilyk, Neonila Korylchuk, Dmytro Maltsev, Mykola Rudenko, Оlena Kozeratska.
TRANSFORMATION OF UKRAINIAN HEALTHCARE TO THE NEW CONDITIONS OF DEVELOPMENT: RISKS, SOLUTIONS,
MODERNISATION OPTIONS……………………………………………….............................................................…………………………47-52
Kozak N.P, Stakhova A.P.
A CASE REPORT OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS…………...................................………………….53-56
Amandeep Singh, Pravesh Kumar Sharma, Ashok Kumar Singh, Chhaya Agarwal, Geetika M. Patel, Kavina Ganapathy.
RELEVANCE FOR DIAGNOSIS, THERAPY, AND STRATEGIES OF GUT MICROBES DYSBIOSIS IN CHRONIC KIDNEY DISEASE: A
SYSTEMATIC REVIEW…………………………………………………………………….......................................................………………57-63
Sharadze D. Z, Abramov A. Yu, Konovalov O.E, Fomina A.V, Generalova Yu.A, Kakabadze E. M, Bokova E. A, Shegai A.V, Kozlova Z.V,
Fokina S.A.
MEDICAL AND SOCIAL ASPECTS OF PREVENTING SPORTS INJURIES AMONG CHILDREN AND ADOLESCENTS………...…64-71
Hisham A. Ahmed, Abdulhameed N. Aldabagh, Abdulsattar S. Mahmood.
COMPARISON BETWEEN PRE- AND POST-OPERATIVELY BOTOX INJECTION IN SECONDARY WOUNDS HEALING…..……72-76
Pantus A.V, Rozhko M.M, Paliychuk I.V, Kutsyk R.V, Kovalchuk N.Y.
EFFECTIVENESS OF THE APPLICATION OF THE DEVELOPED BIOPOLYMER FIBROUS MATRIX WITH CENOBONE® BIOGEL
FOR THE RECONSTRUCTION OF BONE TISSUE DEFECTS OF THE JAWS……………………………………………………………77-84
Sherif W. Mansour, Nesrin R. Mwa, Nafe’ M. AL-Tawarah, Bayan Masoud, Hamzah A. Abu-Tapanjeh, Ibraheem M. Alkhawaldeh,
Mohammad S. Qawaqzeh, Raghad Amro, Sulieman B. Mazahreh.
PREVALENCE OF LEFT/RIGHT CONFUSION AMONG MEDICAL STUDENTS IN MUTAH UNIVERSITY- JORDAN….......………85-89
Sadhanandham S, Preetam K, Sriram V, B Vinod Kumar, Pulkit M, TR Muralidharan.
SEVERITY OF MITRAL REGURGITATION AND ITS ASSOCIATION WITH LEFT VENTRICULAR DYSFUNCTION AND BRAIN-
NATRIURETIC PEPTIDE LEVELS IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE…….........................………90-93
Ahmed J. Ibrahim, Niam Riyadh.
EVALUATION OF MIDPALATAL SUTURE MATURATION IN THREE AGE GROUPS IN 10-25 YEARS USING CONE-BEAM
COMPUTED TOMOGRAPHY…..............................................……………………………………………………………………………….94-100
Mohammed J. Mohammed, Entedhar R. Sarhat, Mossa M. Marbut.
HEPCIDIN AND IRON BIOMARKERS MODULATED IN HEMODIALYSIS PATIENTS………...................................………………101-105
Hussein A. Ibrahim, Ammar L. Hussein.
ESTIMATION OF VON WILLEBRAND FACTOR IN PATIENTS CARDIAC DISEASES………....................................………………106-110
Mohammed L. Abdulateef, Nihad N. Hilal, Mohammed M. Abdul-Aziz.
EVALUATION OF VITAMIN D SERUM LEVELS AND THYROID FUNCTION TEST IN HYPOTHYROIDISM IRAQI
PATIENTS……………………………………………………………………………………......................………………………………..111-113

Mohammed N. Mahmmod, Entedhar R. Sarhat.
HEPCIDIN AND FERRITIN MODULATED IN OBESE MALE…………………………..........................………………………………114-118
Nato Gorgadze, Manana Giorgobiani, Jumber Ungiadze, Vera Baziari, Leila Axvlediani.
EFFECTS OF MATERNAL BLOOD LEAD IN THE PRENATAL PERIOD ON NEWBORNS AND THE SPECIFICS OF THE CONDITION
AT BIRTH……………………………………………………………………………………......................................................……………119-123
Harith S. Aziz, Ammar L. Hussein, Mohamed G. Zakari.
MYELOPEROXIDASE AND COENZYME Q10 MODULATED IN THE CHRONIC KIDNEY DISEASE PATIENTS…..……………124-128
Arnab Sain, Shilpi Awasthi, Oluwafunmilola UKOH (Adeyemi), Kanishka Wattage, Ahmed Elkilany, Adhish Avasthi.
SAFE USE OF FLUOROSCOPY AND PERSONAL PROTECTION EQUIPMENT IN TRAUMA &
ORTHOPAEDICS…………………………………………........……………………………………………………………………………129-132
Azzam A. Ahmed.
SUTURED VERSUS SUTURELESS CONJUNCTIVAL AUTOGRAFT FOR PRIMARY PTERYGIUM……......................................…133-136
Osmolian V, Avsievich Al, Parandiy Va, Okhman Ol, Loginova N.
FORENSIC AND LEGAL SIGNIFICANCE OF HYPNOSIS DURING A CRIMINAL INVESTIGATION….......................................….137-146
Loqman J. Tawq, Ali K. Durib, Esraa S. Jameel.
CONCENTRATION OF MALONDIALDEHYDE IN WIVES INFECTED WITH TOXOPLASMA GONDII WHICH CORRELATES WITH
INTRAUTERINE INSEMINATION IN BAGHDAD’S POPULATION COUPLES…………….............................................……………147-151
Georgi Tchernev, Naydekova N.
MELANOMA AND DYSPLASTIC NEVI DEVELOPMENT AFTER RANITIDINE/RILMENIDINE/МOXONIDINE, LERCANIDIPINE,
ROSUVASTATIN AND VERAPAMIL/TRANDOLAPRIL- NEW DATA/CASE SERIES. THE POTENTIAL ROLE OF NITROSAMINE/
NDSRIS CONTAMINATION IN POLYMEDICATION AS SUBSTANTIAL SKIN CANCER TRIGGERING FACTOR………………152-158
Qutaiba A. Qasim.
HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) SYNDROME AMONG HEMODIALYSIS PATIENTS AND DISEASE
MANAGEMENT STRATEGY………………..........................................................…………………………………………………………159-170
Oleg Batiuk, Iryna Hora, Valeriy Kolesnyk, Inna Popovich, Antonina Matsola.
MEDICAL AND FORENSIC IDENTIFICATION OF PERSONS WHO HAVE BECOME VICTIMS OF WAR CRIMES OF THE RUSSIAN
WAR AGAINST UKRAINE……………………………….........................................................................…………………………………171-179
F. Kh. Umarov, Ju.D. Urazbaev.
PATIENT-RELATED FACTORS AFFECTING THE RISK OF COMPLICATIONS AFTER PRIMARY TOTAL HIP
ARTHROPLASTY…………………………………………………………………………….......…………………………………………180-186
Arnab Sain, Ahmed Elkilany, Arsany Metry, Marina Likos-Corbett, Emily Prendergast, Kanishka Wattage, Adhish Avasthi.
OCCUPATIONAL HAZARDS IN ORTHOPAEDIC PROCEDURES-A NARRATIVE REVIEW OF CURRENT LITERATURE…..…187-190
Dhanya R.S, Pushpanjali K.
IMPACT OF CULTURAL FACTORS ON THE DENTAL HEALTH STATUS AND BEHAVIOUR OF FEMALES IN THEIR GESTATION
PERIOD………………………………………………................................................………………………………………………………191-195
Georgi Tchernev.
MULTIPLE KERATINOCYTIC CANCERS AFTER ENALAPRIL/LOSARTAN INTAKE: POTENTIAL LINKS TO DRUG MEDIATED
NITROSOGENESIS/ CARCINOGENESIS: MELOLABIAL ADVANCED FLAP AND UNDERMINING SURGERY AS OPTIMAL
THERAPEUTIC APPROACH…………………….........................................................................................................…………………….196-199
Subhrajeet Chakraborty, Ankur Khandelwal, Rashmi Agarwalla, Limalemla Jamir, Himashree Bhattacharyya.
ARTIFICIAL INTELLIGENCE: CREATING NEW PARADIGMS IN THE MANAGEMENT OF NON-COMMUNICABLE
DISEASES……………………………………………................................................………………………………………………………200-202
VILCAPOMA URETA LIZVE, AYALA GUEVARA KAREN JANET, JUNCHAYA YLLESCAS VILMA AMPARO, PARIAJULCA
FERNANDEZ ISRAEL ROBERT.
COMPARISON OF THE EFFICACY OF TRAMADOL AND DICLOFENAC IN RELIEVING POSTOPERATIVE PAIN OF
LAPAROSCOPIC CHOLECYSTECTOMY…………....................................………………………………………………………………203-206

GEORGIAN MEDICAL NEWS
No 11 (344) 2023
© GMN 152
MELANOMA AND DYSPLASTIC NEVI DEVELOPMENT AFTER RANITIDINE/
RILMENIDINE/МOXONIDINE, LERCANIDIPINE, ROSUVASTATIN AND VERAPAMIL/
TRANDOLAPRIL- NEW DATA/CASE SERIES. THE POTENTIAL ROLE OF
NITROSAMINE/ NDSRIS CONTAMINATION IN POLYMEDICATION AS SUBSTANTIAL
SKIN CANCER TRIGGERING FACTOR
Georgi Tchernev1,2, Naydekova N2.
1Onkoderma- Clinic for Dermatology, Venereology and Dermatologic Surgery, General Skobelev 26, 1606 Sofia, Bulgaria.
2Department of Dermatology and Venereology, Medical Institute of Ministry of Interior, General Skobelev 79, 1606 Sofia, Bulgaria.
Abstract.
The idea of drug-induced/exogenic Nitrosogenesis is driven by
the possibility of prolonged exposure of the human body to the
inuence of nitrosamines within the drug intake – substances
or contaminants that have been proven to be carcinogenic or
mutagenic one.
Until recently, there was a complete lack of data in the scientic
literature on the relationship between cancer, polymedication
and polycontamination with nitrosamines.
In the last decade, melanoma has been described repeatedly in
the medical literature as a possible side-eect within the intake
of possibly with nitrosamines contaminated medications such
as: Valsartan, Hydrochlorothiazide, Amlodipine, Nebivolol,
Bisoprolol and Perindopril.
However, the contribution of the currently presented new
data (5 new patients) is also due to the establishment of the
possible pathogenetic role (with respect to melanoma) of
several completely new drugs, previously unknown to the
scientic community (potentially/actually contaminated with
carcinogens/nitrosamines), such as: Ranitidine, Rosuvastatin,
Lercanidipine, Rilmenidine, Trandolapril, Moxonidine and
Verapamil.
The leading and connecting link in shared new and old drug
combinations of heterogeneous drug classes (polymedication)
and melanoma development and progression remains again one
and the same : the possible availability of nitroso component in
the frame of exogenous nitrosogenesis according to the ocial
FDA lists of 2023.
The number of drugs shared as contaminated with nitrosamines
after whose intake melanomas occur is increasing.
Nitrosogenesis remains a new beginning, a new understanding
and new interpretation of the carcinogenesis concerning
melanoma, but probably also of cancer in general. Its further
elucidation looks more than promising and is yet to come.
More than worrying at the moment remains the fact that the
scientic community has to clarify if : 1) peak concentrations
of nitrosamines or NDSRIs within the framework of
monomedication or 2) normal concentrations within the
polymedication (catalogued in the list of FDA/ 2023 as
potentially contaminated with hypothetical carcinogens), could
hide relatively short-term risk of the development of real tumors:
cutaneous melanomas and/or their precursor lesions.
The validation of the concept of Nitrosogenesis and its
relationship to Сarcinogenesis, is achieved in practice on the
basis of the following facts: that it is the occurrence of the same
monomorphic clinical pattern (melanoma/dysplastic nevi) ,
developing after the intake of drugs with dierent mechanism of
action, contaminated with nitrosamines / NDSRIs. The unifying
link between the intake of certain drugs and the development
of certain tumours remains the presence of nitrosamines.
Ingredients that are present in drug preparations, identied as
availability and as carcinogenic potency, but not yet reected in
packaging or prescriptions. The question remains: why?
Key words. Nitrosogenesis, nitrosamines, NDSRIs, melanoma,
dysplastic nevi, ranitidine, rosuvastatin, lercanidipine,
rilmenidine, verapamil, trandolapril, hydrochlorothiazide,
nebivolol, bisoprolol, amlodipine, valsartan, perindopril,
polymedication, polycontamination.
Introduction.
According to a number of clinical observations, nitrosogenesis
is a novel concept underlying the generation of cutaneous
tumors, at least as a nonnegligible co-factor [1,2]. This concept
or new model of interpretation concerns keratinocytic tumors as
well as dysplastic nevi and melanoma in particular [3].
The FDA published in 2019 in its ocial bulletin all sartans that
could be actually/potentially contaminated with nitrosamines/
NDSRIs [4].
By 2023, other drugs potentially/actually contaminated
with nitrosamines of various classes are already on the FDA
list - including ACE inhibitors Perindopril, Trandolapril/,
beta blockers/Nebivolol, Bisoprolol/, calcium antagonists/
Amlodipine/thiazide diuretics/Hydrochlorothiazide and
Ranitidine [5,6].
It sounds logical that the combined intake of several drugs
contaminated with nitrosamines would correlate with the
occurrence of multiple or `more severe' melanocytic tumors
as pathology, regardless of the class of drugs in which the
contaminants are found [3].
Not infrequently, however, monomedication can also lead
to the concomitant development of cutaneous melanomas
and/or their precursors [7]. In these cases, it is important to
ascertain whether polycontamination with nitrosamines or
monocontamination with peak concentrations is actually
present: conditions previously uncommented upon.
Polymorbidity and polycontamination are now also clinically
reported to be among the most signicant triggers for the
development and progression of cutaneous tumors, including
melanomas [3].

153
and was sensitive to touch. In parallel, during the last half year
she reported general weakness, loss of appetite, nausea and
vomiting, pain along the course of the spine with numbness of
the upper limbs.
As co-morbidities, she reported arterial hypertension dating
back to 2018, for which she has been taking Nebivolol/
Hydrochlorothiazide therapy 5mg/12.5mg once daily in
combination with Lercanidipine hydrochloride 10mg twice
daily for 5 years.
During the dermatological status, a pedunculated tumor-like
formation in the pubic area with a diameter of 6 cm by 3.5 cm
and a tendency of spontaneous bleeding, with a smooth surface
but irregular pigmentation was found (Figures 3a-b).
CT of the abdomen and pelvis was performed, and the process
was shown to disseminate into the lung, liver and vertebrae.
Treatment of the giant melanoma formation was planned with
In the context of the availability of nitrosamines as modulators
of Nitrosogenesis/Carcinogenesis, we present 5 cases that
demonstrate the real possibility of melanoma and/or dysplastic
nevus development within the context of intake of potentially
contaminated drugs from the sartans group, ACE inhibitors, beta
blockers, calcium antagonists/ Verapamil, thiazide diuretics,
centrally acting sympatholytics/ Moxonidine, Rosuvastatin and
Ranitidine.
We describe once again the association between
polycontamination with nitrosamines/NDSRIs/genome
modiers within polymedication and polymorbidity leading to
the development of dysplastic nevi and cutaneous melanomas.
Case Series.
Case 1.
A 52-year-old patient reports the presence of two nevi in the
abdominal area that he noticed about 10-15 years ago. The
reason for his visit to the dermatology and dermatologic surgery
outpatient clinic is that he has observed a change in size as well
as intermittent bleeding from the lesion under his right mamilla
for the past 1 year.
He reported arterial hypertension as comorbidities dating back
to 2021 and started systemic therapy with Amlodipine 2x5mg;
Moxonidine 1x0.2mg; Hydrochlorothiazide ½ tab. of 25mg for
a total period of 2 years. From 01.04.2023 the previous therapy
was changed to Valsartan 1x160mg, Rilmenidine 1x1mg and
Hydrochlorothiazide ½ tab. of 25mg every other day, for a
period of 8 months to date.
In childhood/youth he was treated long term with Ranitidine
for gastritis and duodenal ulcer.
The dermatological status revealed an asymmetric lesion with
irregular borders about 3.a 1.2 cm in size, with irregular dark
pigmentation and elevation on palpation in the area below the
right mamilla (Figure 1a). The lesion described was suggestive
of cutaneous melanoma. In the area under the left mamilla, a
lesion with a rounded shape and apparently clear borders, about
0.5 cm in size but with irregular pigmentation, was seen, which
was suggestive of dysplastic nevus (Figure 2a).
An elliptical excision with an operative margin of 0.3cm in all
directions was performed on the lesion suggestive of melanoma
(Figure 1b) and an elliptical excision with an operative margin
of 0.2cm was performed on the lesion suggestive of dysplastic
nevus (Figure 2b). Histological verication showed: supercial
spreading melanoma (Clark 3; Breslow 0.79mm) and a
dysplastic nevus. Clean resection lines. Melanoma re-excision
was followed by 1cm eld of surgical certainty in all directions,
histologically veried clean resection lines (Figure 1d).
A CT scan of the head, chest, abdomen, and pelvis with
contrast was performed and showed -no evidence of metastatic
spread. The staging was T1aN0M0. The patient was referred to
the regional cancer clinic for follow-up.
Case 2.
A 71-year-old female patient in severe general condition
was admitted to the outpatient dermatology and dermatologic
surgery clinic for a tumor in the symphysis area. She rst noticed
a dark protrusion about 2 years ago (2021), which slowly grew
to the size of a child's st (6 by 3.5 cm), bled spontaneously,
Figure 1. 1a: Asymmetric lesion with uneven borders about 3 cm in
size, with irregular dark pigmentation and elevation on palpation in
the area under the right mamilla, suggestive of cutaneous melanoma.
1b: Elliptical excision of the lesion with an operative margin of 0.3cm
in all directions. 1c: Postoperative image after the rst excision. 1d:
Melanoma re-excision with 1cm operative margin in all directions.
Figure 2. 2a: A lesion with a circular shape and apparently clear
borders, about 0.5cm in size, but with irregular pigmentation that is
suggestive of a dysplastic nevus.
2b: Elliptical excision of the lesion with an operative margin of 0.2cm
in all directions.
2c: Postoperative nding.

154
near-eld of surgical security, BRAF testing and initiation of
targeted therapy.
Case 3.
A 74-year-old male patient visits the dermatology and
dermatologic surgery outpatient clinic for a slow-growing
pigmented spot on his right foot that he rst noticed about 10
years ago.
As a co-morbidity, he had a known history of arterial
hypertension of about 26 years duration. He has been taking
antihypertensive therapy for 25 years to date Nebivolol 2x5mg,
Zofenopril 2x30mg, Spironolactone ½ tab of 50mg and
Rosuvastatin 1x20mg.
During the dermatological status, a solitary macule with
irregular shape and pigmentation, with indistinct borders and a
size of about 1cm, clinically and dermatoscopically suggestive
of dysplastic nevus, was found in the area of the right foot -
(Figure 4a).
The lesion was removed by elliptical excision with a surgical
margin of 0.3cm in all directions, and the material was sent for
histological examination, which veried a borderline lentiginous
nevus (Figure 4b).
Case 4.
A 61-year-old male patient visits the dermatology and
dermatologic surgery outpatient clinic for a slow-growing
formation on his left forearm that he rst noticed 8 months ago.
He reported arterial hypertension and psoriasis vulgaris
as comorbidities. He started systemic therapy in 2005 with
Perindopril/Amlodipine 5mg/5mg, which he took for about
2 months. He then switched to therapy with Verapamil/
Trandolapril 2x180mg/2mg for a period of 18 years, which he
still takes today.
From the dermatological status, a solitary, pedunculated,
epidermal nodular formation with a depressed surface and
pale pink colour, 1x1cm in size, suggestive of broma, was
noted in the left axilla. Additionally, three nevi of 0.7- 1.1 cm
in size, with heterogeneous pigmentation, irregular shape, and
indistinct margins, suggestive of dysplastic nevi, were observed
in the dorsal region (Figure 5b).
Figure 3. 3a-b: Pedunculated giant cell melanoma, measuring 6/3.5cm,
with irregular pigmentation and spontaneous bleeding.
Figure 4. 4a: Pigmented macule with irregular shape and indistinct
borders, about 1cm in size, clinically and dermatoscopically suggestive
of dysplastic nevus.
4b: Postoperative photograph after elliptical excision of the lesion.
Figure 5. 5a: Postoperative photograph after elliptical excision of a
tumor lesion in the left axilla, suggestive of keratinocytic tumor.
5b: 3 nevi on the back, 0.7-1.1 cm in size, with heterogeneous
pigmentation, irregular shape, and indistinct margins, clinically and
dermatoscopically suggestive of dysplastic nevi.
5c: Postoperative photograph after elliptical excisions of the three
nevi.
Figure 6. 6a-e: Nevi on the patient's trunk with irregular shape,
indistinct borders, and heterogeneous pigmentation, suggestive of
dysplastic nevi.

155
Four elliptical excisions were performed under local anesthesia
(Figures 5a,5c). The materials were sent for histological
verication, which showed that the nodular formation in the
right forearm area histologically corresponded to a verruca with
hyperkeratosis, nevus 1 corresponded to a dermal nevus with
low-grade dysplasia, and nevi 2 and 3 corresponded to a dermal
nevus with high-grade dysplasia.
Case 5.
A 63-year-old patient went to the dermatology and
dermatologic surgery outpatient clinic for examination of moles
he has had for nearly 30 years but has noticed changes in the
color and size of some of them in the past 1-2 years.
He has arterial hypertension as a comorbid condition for which
he has been taking Bisoprolol 1x5mg for 10 years.
During dermatological status, multiple nevi were found on the
patient's torso. There were several irregularly shaped nevi with
indistinct borders and heterogeneous pigmentation, suggestive
of dysplastic nevi (Figures 6a-e).
Seven elliptical excisions were performed under local
anesthesia (Figures 7a-c). Histological verication of the
materials followed, the result of which showed: 1 seborrheic
keratosis, 5 mixed melanocytic nevi with a marked degree of
architectural and cytological dysplasia, and 1 mixed melanocytic
nevus with a mild degree of architectural and cytological atypia.
Discussion.
The common feature between the presented cases is the
intake of a heterogeneous class of drugs and the appearance of
identical tumours or their precursors in the face of dysplastic
moles and melanoma, which developed after a relatively similar
period of drug intake. What has been shared helps to further
clarify the ˝last mysteries˝, while also representing a direct
logical answer to the latter: ˝Are heterogeneous classes of drugs
(with radically dierent mechanisms of action) a key factor
with respect to the development of a monomorphic clinical
nding, such as melanoma and dysplastic nevi in this case ?
Is there any evidence for the availability or identication of a
single potential (or multiple but synergistically acting), real or
hypothetical inducer/contaminant that appears to be common to
all classes of melanoma or cancer initiating drugs in general ?
The answer is : Yes and that might be the nitrosamines.
The expert opinion on this was given in 2018 and rearmed
in 2023 in the ocial FDA bulletins. It conrms the presence
of carcinogens/mutagens/nitrosamines in Valsartan [4],
Hydrochlorothiazide [8], Ranitidine [6] and Amlodipine [5]
taken by our rst described patient . For this reason, it is the
combined (or subsequent) intake of these drugs in the context
of polycontamination with nitrosamines that should not be
surprising for the development of cutaneous melanomas and
dysplastic nevi. Nitroso-Moxonidine, again taken by patient
1, has also been described as being available as a nitroso-
compound but is not yet indexed in the FDA list of potentially/
really contaminated preparations [5].
Monomedication with Valsartan has been described as a
possible inducer of cutaneous melanoma due to its possible
contamination with nitrosamines [9]. Valsartan in combination
with Hydrochlorothiazide has similarly been described as a
melanoma and prostate carcinoma inducer in the context of
potential nitrosamine contamination [10].
The most recent follow-up studies from the United
States are once again conrmatory regarding the use of
Hydrochlorothiazide as a monomedication and the development
of cutaneous melanomas [11].
The role of amlodipine as an ˝additional contribution˝ to
the cumulative daily intake of mutagens in the context of
polymedication has already been discussed in relation to
nitrosogenesis and skin cancer in other scientic works [1,2].
Rilmenidine taken by patient 1 is currently available in various
databases for the determination of nitroso compounds and as
Nitroso-Rilmenidine but has not yet been catalogued in the FDA
list [5]. Its combination with Valsartan and Hydrochlorothiazide
in our described patient 1 could have a synergistic eect in the
context of polycontamination with nitrosamines.
For the rst time in the world literature, prolonged (according
to the history) administration of Ranitidine in childhood due to
gastritis and duodenal ulcer and the subsequent development
of cutaneous melanoma and dysplastic nevi (patient 1), (albeit
after several decades) is also commented.
Due to the lack of clarity regarding the duration of intake and
dose of ranitidine, at present the interpretation of the data appears
to be also somewhat - speculative, but not rejecting the role of
Nitrosogenesis in regarding melanoma pathogenesis. Whether
prolonged Ranitidine treatment is relevant to melanoma and
dysplastic nevus (initial malignant cell clone) generation remains
unclear. However, the initiating point for initial cutaneous
melanoma and dysplastic nevus generation within the potential
contamination of ranitidine with nitrosamines in adolescence/
childhood could be quite possible , if not pivotal. Several decades
later and after initiation of additional combination therapy for
arterial hypertension with Amlodipine and Hydrochlorothiazide
for a period of 2 years, followed by a change in therapy to
Valsartan, Rilmenidine, Hydrochlorothiazide for 8 months,
a change in the shape and size of the pigmented lesions was
observed. Proceeding from the high carcinogenic potency of
Valsartan contamination according to the 2019 FDA list [4], it
would be more than logical to observe a short-term change in
the evolution of lesions.
Figure 7. 7a- c: Postoperative images after elliptical excision of the
lesions.

156
For the rst time, the role of ranitidine in melanoma and
dysplastic nevus generation is thematized worldwide in the
context of its potential contamination with nitrosamines. Also
new in this case is the calcium antagonist Rilmenidine, which
has not been catalogued in the FDA list so far, but after whose
intake (combined) could be associated with the generation of
dysplastic nevi and melanomas in the context of nitrosogenesis.
Nitroso-Rilmenidine is probably under evaluation for
cataloguing in the FDA list.
The de novo occurrence of pedunculated advanced giant
cell melanoma after Hydrochlorothiazide administration was
presented in patient 2 and is entirely and strongly conrmatory,
analogous to American data concerning heterogeneous
collectives linking Hydrochlorothiazide monomedication to the
occurrence of cutaneous melanomas [11,12]. Unfortunately,
these data again do not comment on potential or actual
nitrosamine contamination, which does not, however, exclude
it as a cofactor in the induction of cutaneous melanomas [2,3].
To this intake could be added the intake of the beta blocker
Nebivolol, already described as potentially contaminated
with nitrosamines according to the April 2023 FDA list [5].
Beta blockers but in combination with Valsartan, Amlodipine
and Hydrochlorothiazide have also been recently described
as possible inducers of multiple cutaneous melanomas and
dysplastic nevi within the nitrosamine contamination [3].
The fact that Nitroso-Lercanidipine is a reality , not a myth,
suggests that its cataloguing in the new FDA list update is also
likely to be short-term [13].
The concomitant use of 2 drugs ocially declared as
contaminated in the FDA list, repeatedly formalized in the
scientic literature as possible melanoma inducers (Nebivolol/
HCT), in combination with Lercanidipine (potentially formalized
as possibly contaminated/ Nitroso-Lercanidipine), could be
risky in terms of generation and progression of pedunculated
melanoma in the patient we described (case 2). Three years after
taking potentially/actually polycontaminated with nitrosamines
drugs, the patient developed a de novo advanced , metastatic
giant pedunculated melanoma.
Systemic medication with beta blockers (in patient 3) with
Nebivolol , could be critically considered and would also
classify him as potentially risky with respect to melanoma
pathogenesis and Nitrosogenesis , similar to patient 2.
Rosuvastatin is the other potentially nitrosamine-contaminated
drug existing as Nitroso-Rosuvastatin [14,15], not yet
catalogued in the FDA list [5], but possibly playing a role in
terms of the so-called cumulative carcinogen intake (within the
polymedication polycontamination framework) and subsequent
melanoma generation. For Spironolactone and Zofenopril taken
concomitantly, data on nitrosocontamination and FDA list
presence/cataloguing are currently lacking [5].
In Patient 4, we describe the occurrence of dysplastic nevi
after a short-term initial intake of Perindopril and Amlodipine
for 2 months (combined preparation), followed by an irregular,
but prolonged intake of Verapamil/Trandolapril (combined
preparation) for 18 years. The following should be emphasized:
the development of dysplastic nevi after taking amlodipine
in combination with Perindopril is not new to the academic
community and has been described in the literature, although it
is not always reected in the title of some published articles [16].
The occurrence of melanoma after Perindopril intake is also not
new , and this intake could condition the staged occurrence of
keratinocytic tumor such as BCC additionally [17]. International
data from the United States in the recent past associate the risk
of cutaneous melanomas (and logically their precursors) with
the intake of ACE inhibitors [12], and the same is associated
with the risk of basal cell carcinomas : for melanomas- adjusted
OR (95%CI): 1.71 (0.97-3.00), i.e. about 171% risk (similarly,
part of this risk concerns melanoma precursors in the face of
dysplastic nevi). Amlodipine and Perindopril have been on the
FDA list since 2023 as potential carcinogens with potencies of
5/FDA table [5], respectively.
Patient 4's therapy was changed to Verapamil/Tranodolapril
for a period of 18 years. And while Trandolapril is available
on the FDA list as of 2023 for ʺhypotheticalʺ carcinogen-
contaminated drugs [5], nitroso-verapamil is also now a reality
and its cataloguing on the (FDA list) is probably forthcoming
[18,19].
This in practice makes the combined intake of 2 potentially/
actually nitrosamine-contaminated drugs (Verapamil/
Trandolapril) over the years quite feasible. Hence, accordingly,
the occurrence of dysplastic nevi after their administration
should not be puzzling in the least.
The fth patient described in the publication had a history
of multiple melanocytic nevi since childhood, clinically and
dermatoscopically suggestive of dysplastic ones, with a median
age of 30 years, as well as a change in some of them dating back
no more than 2 years.
He had been taking Bisoprolol for 10 years, and Bisoprolol
was catalogued by the FDA list for 4 potentially carcinogenic
drugs [5].
A number of publications in the world literature have
thematized the positive role of beta blockers in patients with
melanomas [20-22], but the fact that this information remains
at present somewhat one-sided interpreted, manipulative, and
speculative, but should not be downplayed because of the
following few circumstances: 1) these articles thematize the
role of the active substance in relation to (already) pre-existing
melanomas, 2) interpretation of the data, which is to some
extent unclear, nds, however, that patients were taking beta-
blockers before the tumour/melanoma occurred, and 3) no one
comments on the actual or potential role of beta blockers and
their available contaminants in the form of nitrosamines in the
generation of melanomas within the pre-manifestation drug
intake [1-3].
In practice, the interpretation of the shared literature data [20-
22] could also be the following: patients who took a beta blocker
(contaminated with nitrosamines) subsequently developed
cutaneous melanomas whose progression remained temporally
delayed due to the action of the pure, active ingredient.
Beta blockers remain melanoma generators according to these
data [20-22], however, the main pathogenetic inducer has not
been thematized in the works, and this is only happening in
2023 through the formalization of the FDA list for nitrosamine
contamination of beta blockers [5].

157
The three publications in question came out after 2018, or the
year of the FDA announcement of valsartan contamination.
There remains the logical question, with a slightly ironic
note: ˝Do I (or somebody) want to take a beta blocker that is
contaminated with nitrosamines and leads to the formation of
melanoma whose progression will be probably slowed down
˝afterwards˝ by the active ingredient of the same drug?ʺ
The purposeful absence or underreporting of this information
in the international articles [20-22] is certainly unable to shift
the focus away from the role of beta blockers (nitrosamine
contaminated) in relation to melanoma generation [1-3], and it
is these articles – [20-22] that are indicative and conrmatory of
the thesis of the importance of nitrosogenesis/its pathogenetic
role in melanomas [20-22].
No one disputes that it is likely that the active ingredient in
certain collectives of patients is able to (probably) slow the
progression of melanomas that have already arisen [20-22], but
these tumors arose within the context of already available intake
of beta blockers [20-22] actually or potentially contaminated
with nitrosamines.
This is where the indirect contribution of these papers lies-
they focus attention on beta blockers intake and melanoma
development as a topic [20-22], from which the thesis of
Nitrosogenesis of melanoma, caused by the previous intake
of beta blockers, potentially/actually contaminated with
nitrosamines, emerges again.
Once again, the development of ʺreal tumors/melanomasʺ
after combined intake of ʺhypothetical carcinogensʺ within the
framework of polymedication and polymorbidity is presented.
The occurrence of melanoma precursor lesions and lentigo
maligna after the administration of sartans and hydrochlorothiazide
has recently been described in the dermatological literature,
discussing the role of polycontamination with nitrosamines
within the framework of the combined drug administration
[23]. International groups of experts consider polymedication
with a heterogeneous class of medication within the framework
of polycontamination with nitrosamines as extremely risky, at
that - in the short term [24].
Conclusions.
1. The paper and data are conrmatory in nature regarding
the already known hypothetical contamination (real/potential)
of thiazide diuretics (Hydrochlorothiazide), ACE inhibitors
(Perindopril) and calcium antagonists (Amlodipine) with
respect to Nitrosogenesis and cutaneous melanoma development
according to FDA.
2. The data are again conrmatory with respect to Nebivolol
and Bisoprolol and their possible association for melanoma
generation within the polymedication and polycontamination.
3. For the rst time in the world literature, the role of calcium
antagonists: Nitroso-Lercanidipine and Nitroso-Rilmenidine
within polymedication as possible candidates for inclusion
in the list of FDA , concerning the available potential/actual
contamination with nitrosamines/NDSRIs is thematized. And
the subsequent development of cutaneous melanomas.
4. The same applies to the intake of Nitroso-Moxonidine, so
far absent from the FDA list , but possibly a preparation that
could be included soon.
5. The contribution of the data presented here is signicant
and extremely important, describing for the rst time in the
world literature: a link between the intake of Ranitidine and
the development (subsequently) of cutaneous melanoma and
dysplastic nevi (in the context of subsequent polymedication and
polycontamination of the drugs/ or the so-called nitrosogenesis
). Ranitidine is catalogued in the FDA list as a potentially
contaminated drug with a carcinogenic potency between 1 and
3, which undoubtedly conrms the role of nitrosogenesis in the
generation of melanomas.
6. Analogous to the data for ranitidine are those for
Rosuvastatin intake, currently uncatalogued from the FDA list
but available as Nitroso-Rosuvastatin. And after whose intake in
the framework of polymedication (Nebivolol/ Zofenopril (?))/
polycontamination and polymorbidity, developed a melanoma
precursor lesion.
7. Combined administration of the ACE inhibitor Trandolapril
and the calcium antagonist Verapamil within the context
of nitrosamine contamination should also be regarded as
potentially risky and as an innovative new idea concerning
melanoma pathogenesis. Trandolapril has been catalogued in
the FDA list since 2023 and nitroso-verapamil is currently a
reality, and not a virtual one.
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