BACKGROUND:Drug-induced carcinogenesis is a matter of huge popularity and the subject of in-depth research over the last few years. According to the literature, dopamine agonists and acetylsalicylic acid fall into the list of drugs likely to potentiate the development of cutaneous melanoma. However, according to recent data, widely used angiotensin receptor blockers (ARBs) for the treatment of arterial hypertension, also carry a risk of malignancy development. The content of probable carcinogens, such as NDMA or NDEA in the drug valsartan (ARBs), causes the product to be withdrawn from the market. Recent experimental data suggest that another angiotensin receptor blocker-losartan also stimulates cell adhesion and melanoma cell invasion.CASE REPORT:We present a 70-year-old patient who has been on systemic therapy with a combined drug of amlodipine and valsartan since 2008 and only valsartan from 2015. Three years after the first intake of valsartan (2011), the patient developed a pigment lesion on the right arm. Approximately 2.5 years after doubling the dose of valsartan, the patient observed a progression in the size of the lesion, which was the cause of the dermatological examination and hospitalisation for surgical removal. The melanocytic lesion was removed by radical excision and a surgical field of 0.5 cm in all directions, followed by histological verification, which found the presence of cutaneous melanoma with a tumour thickness of 3 mm. A re-excision was planned with an additional surgical field of 1.5 cm in all directions combined with parallel removal of a draining lymph node.CONCLUSION:The case is indicative of two things: 1) the possible triggering of melanoma within the systemic treatment with valsartan; and 2) the necessity for optimization of melanoma surgery within the one-step melanoma surgery, which in this case would result in a single surgical excision of the primary lesion, with an operational security field of 2 cm in all directions, along with the removal of a draining lymph node.

BACKGROUND:Melanoma appears to be a malignant disease, whose development can be potentiated by different drug groups. More and more data are in favour of the claim that commonly used antihypertensive drugs also contain the risk of developing melanoma. The most evidence is that angiotensin receptor blockers may be carcinogenic. Two representatives from this group, valsartan and irbesartan, produced by certain pharmaceutical companies are being withdrawn from the market due to finding content of NDMA and NDEA, which are believed to be potent carcinogens. Another representative of this group, losartan, according to in vitro data, potentiates cell adhesion and invasion of human melanoma cells.CASE REPORT:We present a 45-year-old man with arterial hypertension. For year and a half/two years, the patient is on systemic therapy with Aspirin and Irbesartan/Hydrochlorothiazide. The patient also reported about the presence of a pigmented lesion in the abdominal area, which occurred 5-6 years ago, before the onset of cardiac therapy. According to him, there was a change in the colour and size of the lesion within the framework of cardiac therapy (from 1.5-2 years). Innovative one step melanoma surgery was performed, and the lesion was radically removed with a 1 cm operational safety margin in all directions within one operative session. The subsequent histological verification found the presence of thin melanoma.CONCLUSION:Drug-induced melanoma turned out to be a problem of significant importance. The group of angiotensin receptor blockers should be investigated more thoroughly and in detail on the probability of potentiating carcinogenesis. We describe an interesting case showing the progression of pigment lesion to melanoma as a possible result of irbesartan therapy, i.e. we share a theory that differs from that of drug-induced de novo melanomas. It should not be overlooked the fact that another widely used drug-Aspirin, is also likely to potentiate the development of melanoma. Furthermore, the case is indicative of the use of one step melanoma surgery in a melanoma patient with a thickness less than 1 mm.

BACKGROUND:One step melanoma surgery is a new surgical approach by which specific groups of patients with cutaneous melanoma may be operated only by or within a single surgical session. Until now, the Bulgarian Society for Dermatologic Surgery (BULSDS) has presented models of clinical behaviour, in which preoperative measurement of tumour thickness in combination with echographic measurement of the locoregional lymph nodes could lead to the conduct of the so-called one-step melanoma surgery. Although this one step surgery currently does not fit in the recommended guidelines, it ensures compliance of the recommended boundaries of operational security while saving patients a repeated excision and relieves the healthcare institutions or the patients themselves financially.CASE REPORT:We at this moment present another case from the Bulgarian Society for Dermatologic Surgery (BULSDS) of one step melanoma surgery with a perfect end result, where the tumour thickness was not preoperatively determined by high-frequency echography. Preoperative assessment of tumour thickness was performed based on the clinical picture and dermatoscopy. The histologically established tumour thickness was identical to the preoperative assessment, i.e. <1 mm. Removal of the melanocytic lesion was performed with operational security field of 1cm in all directions, where, as a rule, no further removal of the draining lymph nodes is required.CONCLUSION:One step melanoma surgery has two significant advantages: 1) it saves a re-excision in certain groups of patients, which in turn is 2) significantly more favourable from a financial point of view. Its applicability in the appropriate groups of patients and the postoperative (although in a limited number of patients) results achieved indicate the need to optimise the current algorithms and direct them individually to each patient. Guidelines may not and should not be unified or set strict limits given the fact that they show a significant level of variability themselves regarding some key moments in the initial surgical treatment of melanoma. More than 10% of the primary melanoma cases refer to thin melanomas, and dermatoscopy and clinics are a sufficient method of optimising the planned surgical excision.

BACKGROUND:With the newly described one step melanoma surgical approach, some patient groups could be successfully treated within one surgical session. Depending on the tumour thickness (measured preoperatively) at a later stage (also depending on the ultrasound findings of the locoregional lymph nodes) the respective surgical intervention is planned with the respective field of surgical safety (one-stage melanoma surgery with or without removal of lymph nodes). The innovations could make to some extent some of the already existing algorithms more difficult (due to the introduction of a high-frequency ultrasound to determine the tumor thickness preoperatively as an absolute prerequisite for dermosurgical centres), but it would also lead with absolute certainty to better or least optimal results regarding the prognosis, the side effects and the financial factor also.CASE REPORT:We present a patient from the Department of Dermatology, Venereology and Dermatologic Surgery at the Medical Institute-Ministry of Interior (MVR-Sofia), treated with the one-step melanoma surgery method with perfect final results. The preoperative tumour thickness determined via ultrasound and the postoperatively measured histological tumour thickness was identical: between 0.98 and 1 mm, which allowed removal of the melanoma lesion with a field of surgical security of 1 cm in all directions and did not require additional removal of a draining lymph node or excisions.CONCLUSION:Thanks to this new approach, some patients could avoid one surgical intervention, which could be interpreted as a significant advantage or probably also survival benefit. This methodology and its successful application were first officialised by the representatives of the Bulgarian Society for Dermatologic Surgery- (BULSDS), and the purpose of this action, in general, is to fully improve clinical management of patients suffering from cutaneous melanoma in terms of compactness by 1) reducing the number of unnecessary surgeries or the number of surgical interventions in general; 2) reducing side effects occurring in surgeries and 3) introducing a serious optimization in terms of financial resources needed or used in the second hospitalization of patients. The question remains open whether the accepted or the current recommendations for surgical treatment of melanoma will be transformed or adapted for the matching patient groups.

BACKGROUND:Skin, nervous tissue, dopamine and melanoma share a common neuroectodermal origin. Hence, processes that modulate nervous tissue formation, patient mental status, motor regulation of individuals, and skin cancerogenesis are inextricably linked. Psycho-neuro-endocrine oncology (or dermato-oncology), i.e. P.N.E.O., is a new model or trend in medicine and science presented for the first time in the world literature by us, that aims to examine the relationship between the mental state, the hormones and the malignant transformation. Schizophrenia and Parkinson’s disease are the two main patterns of disease where the main symptoms are related to dopamine levels in the human body. According to our analyses of the available literature, the amount of dopamine is related to the incidence of melanocytic or non-melanocytic cutaneous tumours in patients with central nervous system diseases and those affecting the motor function and coordination. Such patterns of interaction are extremely indicative of the elucidation of the ubiquitous hypothesis or statement: “My illness is on a mental basis, caused by stress …”CASE PRESENTATION:We present a 44-year-old patient with untreated schizophrenia for approximately 25 years, associated with advanced acral localised melanoma. Schizophrenia is generally associated with a higher level of dopamine, which is also a key precursor to melanin synthesis. After a careful analysis of all literature on melanoma in patients with 1) treated and untreated schizophrenia, 2) those with untreated and untreated forms of Parkinson’s disease, it would be logical to conclude that the high level of dopamine in the described patient groups is a risk factor for the development of melanoma.CONCLUSIONS:The possible mechanisms for the occurrence of malignant melanoma within the so-called psycho/neuro/endocrine oncology (P.N.E.O.), as well as the effective methods of prevention, are under discussion.

BACKGROUND:Innovations in medicine are often due to the simplicity of a certain activity, interaction, even counteraction, or a mistake leading to a subsequent final optimal outcome. Innovations could also be due to conclusions based on targeted clinical or sporadic, as well as completely random observations. The genius of an approach or statement is often based on the “iron logic”, which in turn is based on irrefutable data or facts. These are often observations or results from actions that happen right before our eyes and provide advantages or prerequisites for the better future development of things (in this case, disease) concerning certain groups of people (in these case-patients). When the clinical results achieved following an inevitable introduction of certain methods or innovations speak eloquently of a number of advantages in terms of 1) spearing effect on the patients, 2) better control or prevention of possible local and/or distant metastatic spread 3) better financial balance for the health institutions and patients, …, then even the “Gods of certain latitudes” should be silenced. We at this moment present a completely new method or approach for surgical treatment of cutaneous melanoma that once again proves the effectiveness of one-step melanoma surgery, which was successfully first officialised in the world literature again by the Bulgarian Society of Dermatologic Surgery, (BULSDS). In some cases, this method does not even require the preoperative use of a high-frequency ultrasound for determining the tumour thickness.CASE REPORT:In patients with advanced stage of cutaneous melanoma, removal of a primary draining lymph node and/or locoregional lymph nodes is often performed simultaneously. However, it remains unclear why in patients with early-stage (or intermediate, with moderately thick melanomas) disease high-frequency ultrasound is not applied as a routine method of determination of tumour thickness? Meanwhile, re-excision is required following histopathological verification? Is it necessary to have 2 surgical interventions? The two surgical interventions are a burden for the patients and create prerequisites for contradicting opinions, statements, and subsequent results, which ultimately slows down the patient’s staging and the introducing more precise treatments. Based on the logic (and further aided by the clinical picture and dermatoscopy), we decided to operate selected cases of patients with cutaneous melanomas with a field of surgical security of 1cm in all directions when clinical, and dermatoscopic data are indicative of melanoma in situ or thin melanomas (less than 1 cm). Optimal results were achieved, with one surgical intervention and subsequent rehospitalisation spared for the patient.CONCLUSIONS:An answer to the question whether it is better not to follow the guidelines strictly (since, as a rule, they are generally recommended and somewhat misleading in certain circles of specialists, and as we have already found, also lead to unjustified logical secondary excisions), or update t...

BACKGROUND:Drug-induced melanoma is a topic, concept or “reality” becoming more and more popular as the list of drugs considered as potential inducers of cutaneous melanoma is constantly growing. Interesting and current at the moment is the question/dilemma of “Irbesartan induced melanomas” and “Valsartan induced melanomas”! The following questions are without answers: 1) the general risk which angiotensin receptor blockers contain for potentiating the carcinogenesis and cancer development (as a whole); 2) available officialized data for withdrawal from the market of products with valsartan and irbesartan due to detected potential carcinogens-NDMA/NDEA, and 3) the missing official information on the most likely forms of cancer potentiated by these drugs. That is precisely why many questions remain open, and the inevitable assumption arises for the key, although according to some conspiratorial role of so-called “pharmaceutical giants” in the concept of drug-induced malignancies.CASE REPORT:We present a 72-year-old man with arterial hypertension in connection with which he is taking Irbesartan 300 mg (1-0-0), Amlodipine 5 mg (0-0-1) and Moxonidine 0.2 mg (0-0-1). The patient reported the presence of pigment lesion in the head area, which dates from many years and 3 years ago it was at the size of the nail plate on the index finger. Irbesartan therapy dates from 1.5-2 years, and according to the patient 1.5-2 years after the start of irbesartan therapy, the lesion grew sixfold, accompanied by sensitivity and discomfort in the area. Clinically and dermatoscopically the lesion had data on superficial spreading cutaneous melanoma. Tumour thickness ≤ 1 mm was measured preoperatively by ultrasound. The so-called one-step melanoma surgery (OSMS) was performed, and the lesion was removed by elliptical excision with an operative surgical margin of 1 cm in all directions within one operative session. The subsequent histological study (and screening staging) found that it was a superficial spreading melanoma stage IA (T1bN0M0).CONCLUSION:Possible, but unlikely, in our opinion, is that the intake of angiotensin receptor blockers (in particular irbesartan), and the progression of benign precursor lesions to malignant do not have a direct relationship. The growing number of data in the literature for drug-induced melanoma and massive withdrawal of products with valsartan and irbesartan due to the content of probable carcinogens speaks, however in favour of the opposite, namely that it is more likely to speak about established dependence than of a sporadic association. Drug-induced melanoma-rather a reality than a myth.

One step melanoma surgery (OSMS) is applicable to all patients with clear clinical and dermatoscopic criteria for thin cutaneous melanomas or melanoma in situ lesions, even without the need for preoperative tumour thickness measurement. Amelanotic melanomas and melanomas with clinical and dermatoscopical features for regression zones could be problematic when applying the OSMS.  The methodology could be also applicable to all groups of patients where the tumour thickness could be measured preoperatively/by ultrasound (while in parallel also determining the status of the locoregional lymph nodes). For tumours with a tumour thickness between 2 and 4 mm, but also over 4mm the OSMS seems to be the correct choice.