The One Step Melanoma Surgery (OSMS): A New Chance for More Adequate Surgical Treatment of Melanoma Patients!?

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

One Step Surgery for Cutaneous Melanoma: “We Cannot Solve Our Problems with the Same Thinking We Used When We Created Them?â€

One step melanoma surgery is, in fact, an innovative combined method for diagnosis and treatment of cutaneous melanoma (at the same time). The methodology allows an accurate assessment of the actual status of the affected patients by 1) clinical status, dermatoscopy, high-frequent ultrasonography (HFUS) of the pigmented lesion (eventually in combination with normal lymph nodes ultrasonography), followed by a single surgical intervention. Within this intervention, the primary tumour is removed with the appropriate surgical field, with or without parallel detection and draining lymph node biopsy (depending on the established tumour thickness). Removal of the lymph node may, in turn, be associated with or without locoregional lymphadenectomy, which is determined by its macroscopic appearance, established intraoperatively or after the histopathological evaluation. The methodology is sparing, innovative, easy to apply, tested in its functionality and logically justified. For an unknown reason, this methodology is not applicable in melanoma treatment’s guidelines in Europe and America. In Bulgaria and France, however, there are centres and hospitals that apply the technique mentioned above with enormous results, in particular in Bulgaria, the methodology is getting more and more improved to the current moment. Based on the above, as well as on the scant experience, we may share the opinion that the current melanoma treatment’s guidelines need major corrections in their recommendations, which are not optimal for patients due to the following facts: (1) the adverse effects on patients as a result of the necessity of at least 2 surgical interventions; (2) the frequent occurrence of changes in the lymph flow after the primary excision; (3) the frequent non-obtaining of the suggested in the guidelines terms for re-excisions with or without sentinel lymph node removal; and (4) the creation of additional financial difficulties for the patients in the framework of two unneeded hospitalizations

Novel Surgical Approach in Сutaneous Melanoma Patients: ʺDaring Ideas Are Like Chessmen Moved Forward. They May Be Beaten, But they May Start a Winning Game!?ʺ

For the first time, but again, we propose the idea of a one-step melanoma surgery as a "golden, unified standard" that should be at least discussed and, possibly accepted shortly as the "gold standard" for the treatment of patients with skin melanomas. Critical points or comments have been made to the current melanoma's treatment approach, which has been "transcendently followed" for years and which, according to some colleagues, is not logically justified. This approach needs serious changes, the only goal of which is to achieve a better outlook for the patients.Although the proposed by us approach is not even a possible option in the European and American recommendations for the treatment of melanoma, it finds widespread use (or acceptability) in clinical practice in the form of specific, individually informed consent. Guidelines are not mandatory, and standards are not always met. Whether "good medical practices" will prevail as a logic and stereotype of clinical behaviour, whether they will be finally recognised and whether they will find an extra international response is unclear at the moment. However, the fact that they are enforced with success, indirectly speaks that the "wave of change" is already rising and the hope is to "remove the debris" and illogically justified decisions often defined by the American dermatological school as "expert". The choice of right solutions lies in following the logic, as well as in its simplicity. Often these decisions are in front of our eyes, but we look at the distant horizons: "Do we want to be discoverers?" Without even trying to give a simple answer to the question: "Aren't the treasures very often in front of us?

Global Dermatology: Learning from the Past but Still Learning from the Best?

If we try to draw conclusions about events, analyse data or results (in one or a certain area) and clarify our unknown points in standard or non-standard ways, this leads to the transfer of experience from one area to another. How do we want to follow guidelines, while the most of the obligatory laws are not followed, for example? The aim of prescriptions or recommendations in medicine, for example, (or the laws of a country that do not usually apply to particular classes or castes, as well as business rules) is to give guidance on how it would be appropriate to help people or ourselves (as we have already mentioned) and the people themselves. Unfortunately, this behaviour is also characteristic of developed societies that dictate the rules and try to help ... to people, as well. If we come deeper into the system of mutual aid in medicine, it is unfortunate that sometimes the condition of this kind of ʺecosystemʺ (or any of the ecosystems described) is worse than the best tragic-comedy. Unfortunately, the "ecosystem of medicine" is also subordinate and slaves somehow to the stronger "ecosystems" as politics and business and is dependent on them, but for evil or good, these ecosystems have glimpsed at times, no matter what are the motives, which provoke them! And they are most often ... once again personal. Although in a number of Eastern European countries, it was unthinkable to even undesirable until recently, that dermasurgery and dermatooncology to be part of modern dermatological societies, the insatiable thirst for growth of young specialists, as well as the impact of Western schools, on their formation as a kind of new hope proved to be stronger in the formation of dermatosurgery, not only all over the world, but also in particular in the Balkans and Bulgaria. These units are gradually being introduced as an indispensable part of any modern clinic, and this part guarantees the best results (in patients with dermatosurgical or dermatooncological needs). The globalisation of dermatology and dermatological science has led to the introduction and involvement of additional auxiliary units, based on a more global concept of the interdisciplinary concept that encompasses psycho-neuroendocrine dermatology which provides a good explanation for some unexplained diseases, such as vitiligo, for example

Innovations and Innovative Approaches or Pseudo-Innovations in the Context of General Globalization? It's Time to Wake Up!

Globalisation, scientific and technical progress are the basis of numerous innovative therapies for oncologic and non-oncologic diseases. It is another matter how much and by whom they are desired, and whether they have to be applied. When and how often? Innovative approaches should go towards simplification, universal distribution and application while at the same time analysis between the potential initial investment and the achieved final result should be made. An illustrative example for this is the targeted therapy for melanoma with its low baseline criteria or basic rules for its surgical treatment. Another example could be the confocal microscopy in the context of dysplastic nevus syndrome. Therapies for various autoimmune diseases should also be considered critically. In the current OAMJMS issue, as well as in some of our other ideas and statements reported also in OAMJMS, we are trying to answer at least to a part of these dilemmas, to provoke a critical point of view and to ask some simple questions: “Should any innovation be considered as a face value? Which is potentially beneficial for our patients? How could we regulate the processes to minimise the need for expensive medications for certain diseases? And, of course, we are also turning to our own mistakes by visualising the results of them

Carcinoma cuniculatum in course of etanercept: blocking autoimmunity but propagation of carcinogenesis?

Carcinoma cuniculatum (CC) or verrucous squamous cell carcinoma is a rare variant of squamous cell carcinoma with low incidence of metastasis. It mainly affects men during the fifth-sixth decade of life, arising mostly on the weight-bearing surface of the foot, but it can also be found in other body areas. The favorable effects on the psoriatic, rheumatoid, juvenile polyarthritis as well as the ankylosing spondylitis after the application of Tumour Necrosis Factor (TNF)-alpha inhibitors, like etanercept, presume the availability of similarity between the etiopathogenetic mechanisms which are responsible for the generation of the inflammatory cascade. According to the latest studies, the sensitivity of the patients to TNF-alpha inhibitors could be genetically determined and may also be due to certain genetic polymorphisms of the NLP3 and CARD8 zones of the inflammasome. The blocking of the inflammatory reaction within the borderlines of the psoriatic arthritis could also be accepted as something of a "double edged sword". There is a growing volume of literary data which informs us of the clinical manifestation, not only of skin, but also of other types of tumors after the application of TNF-alpha inhibitors. This inevitably generates the hypothesis that within a certain group of patients the TNF-alpha inhibitors have some additional, and currently obscure, effects on presumably key regulatory proteins of the so-called extrinsic apoptotic pathway. Other proteins of the human inflammasome could be also implicated in the regulation of the programmed cell death and the carcinogenesis - there are speculations, that the adapter protein, ASC/TMS1, could be one of these. The present study describes the case of a patient who developed a rare form of skin tumor - epithelioma cuniculatum - whilst undergoing etanercept therapy for psoriatic arthritis. Under discussion are the possible critical connections in the complex regulatory "networks" of the inflammatory processes, the programmed cell death (apoptosis) and the carcinogenesis which, in the near or distant future, could become the objects of a targeted therapy

Primary Regressive, But Metastasizing Melanoma!?

BACKGROUND: Cases of regressive melanomas represent a diagnostic and therapeutic challenge because time intervals between the presence of the primary tumour formation, the metastasis and the involution of the primary tumour may intertwine or occur at different times. The regression of cutaneous melanomas does not necessarily guarantee prevention from the development of locoregional or distant metastases. There are cases in which the prognosis of patients with the development of subsequent metastasis within regressive melanomas may be better depending on the number and location of metastases. CASE REPORT: We are presenting a 42-year-old patient with two timed removals of enlarged inguinal lymph nodes within one year, as the subsequent histological examination identified histopathological data for metastasis of melanoma. BRAF testing was positive for BRAF mutation. Within the anamnesis, it was further clear that the patient had an irritated melanocytic lesion in the lateral right thigh area, which over the time disappeared and shortly after that, the enlargement of locoregional lymph nodes has been noted. CONCLUSION: In the presented case prognosis and therapeutic options for treatment of patients with regression melanomas and subsequent development of lymph node metastasis have been discussed. Currently, there is no consentaneous opinion on the applicability of the early adjuvant therapy with targeted therapies or immunotherapy in patients with regressive and non-regressive type melanomas. We suggest and share the idea that early adjuvant therapy may be beneficial generally in patients with stage III melanomas

Drug-Induced Melanoma: Irbesartan Induced Cutaneous Melanoma! First Description in the World Literature!

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

Giant Pelvic Neurofibroma in Patient with Plexiform Sciatic Neurofibroma and Neurofibromatosis Type 1

BACKGROUND: Neurofibromatosis is a genetic disease with an autosomal dominant type of inheritance. It is a multisystem disease in which, besides skin manifestations, there is a possibility for the involvement of other organs and systems, and an atypical variant of neurofibromatosis type 1 can also be observed- the so-called plexiform neurofibroma. In patients with this inherited disease, mortality is higher due to the existing risk for malignant transformation and development of malignant peripheral nerve sheath tumours (MPNSTs) or neurofibrosarcoma. CASE REPORT: We present a 25-year-old woman with neurofibromatosis type 1 and a family history of the disease-father and grandmother with NF-1, with fatal outcome in the grandmother as a result of malignant transformation to neurofibrosarcoma. The patient has clinical data for multiple cafés- au- lait spots on the skin of the trunk, upper and lower limbs, and plexiform tumour formation in the seating area. From the performed imaging diagnostic there are available MRT data for 1) giant pelvic neurofibroma, 2) plexiform giant neurofibroma in the subcutaneous fat on the right thigh and gluteal fat tissue to the right, passing through the midline in the area of the external genitalia, leading to deformation of the front wall of the sacrum with bilateral meningoceles and 3) diffuse involvement of the bladder wall from the process in the area of the trigonum vesicae felleae/the two urethral ostium, as well as 4) the presence of neurofibromas in the course of the iliac vessels on the right. Surgical removal of the oval pelvic formation, identified as neurofibroma was planned, as well as the initiation of systemic therapy with Sirolimus for the plexiform sciatic formation, infiltrating the bladder. CONCLUSION: Neurofibromatosis type-1 is a problematic disease due to the parallel systemic involvement of different organs and systems, which can be both limited and diffuse. Limited tumour lesions in the form of neurofibromas with diverse localisation (as in the patient we describe) could be surgically removed without difficulty. On the other hand, the diffuse involvement of internal organs within a giant, network-3spreading plexiform neurofibromas (as in the described patient) makes interdisciplinary interventions impossible, and therefore therapeutic alternatives should be considered

Valsartan Induced Melanoma?! First Description in Medical Literature!

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