MORPHEAFORM BCC OF ALA NASI: A SUCCESSFUL DERMATOSURGICAL APPROACH BY TRANSPOSITION FLAP FROM THE ADJACENT AREA. CONTAMINATION OF VENLAFAXINE, BISOPROLOL AND OLANZAPINE WITH NITROSAMINES/NDSRIS: THE MOST LIKELY CAUSE OF SKIN CANCER DEVELOPMENT AND PROGRESSION.

Two steps are able to lead to a significant decrease in the incidence of skin cancer overall and/or to its parallel and successful surgical treatment. The first step concerns its non-occurrence or less frequent clinical manifestation and is largely related to the modern concept known as prevention, but not the one mainly related to solar radiation, but: 1) informing patients about the possible contamination of certain drugs with carcinogens/nitrosamines/NDSRIs and 2) making clinicians aware of the modern concept of limited to completely eliminated intake of nitrosamines/NDSRIs in medications. The ineffectiveness of either of these entities could in all likelihood be seen as one of the major causes of the headline growth in the incidence of skin cancer and keratinocytic cancer in particular. It is also because of this fact that the sun protection so recommended and advertised has been shown to be ineffective, yet it remains universally advertised. Polycontamination with Nitrosamines/NDSRIs within multimedication in polymorbid patients is the most serious obstacle (at the moment) for the current concept of skin cancer prevention to become a reality. The announced official "hypothetical contamination" of more than 250 drugs worldwide by the FDA in April 2023, and the establishment of permissive concentrations for 5 classes of carcinogenic activity of the nitrosamines/NDSRIs - effectively make any preventive step more than impossible or meaningless. The open question remains, how were the 5 subgroups for hypothetical carcinogenic potency of the carcinogens contained in the drugs created? On the basis of what data? What tumors occurred when these concentrations were exceeded? Data that remains hidden from the public and end users, but also data that guarantees the development of real (not hypothetical) skin tumours. The new FDA regulations also do not comment on the issues concerning the use of "hypothetical carcinogens" in the context of polycontamination and polymedication in polymorbid patients. Because of this fact, the follow-up of actual carcinomas after the intake of multiple "hypothetical carcinogens" would also seem to be not unimportant. And it turns out to be quite real and sobering to say the least. The second step, which concerns the successful treatment of skin cancer, is its early surgical treatment. This is the most promising approach, regardless of whether patients are exposed to permanent intake of carcinogens/nitrosamines/NDSRIs in the drugs. We report an 86-year-old patient, who, as part of his polymedication and polymorbidity, takes 3 drugs that, according to the official FDA list of 2023, have strictly defined reference limits for potentially available "hypothetical carcinogens": bisoprolol/carcinogenic potency class 4, olanzapine/ carcinogenic potency class 5 and venlafaxine/ carcinogenic potency class 1. The described patient developed "real carcinoma" after combined long-term intake of the "hypothetical carcinogens" announced in the official FDA lists from April 2023. Proceeding from common sense, regulators in the face of the FDA should have already long observed the development of a heterogeneous type of tumors to be able to determine 1) the potency of the 5 subclasses of carcinogens in the drugs and 2) their reference values. Moreover- they should also have the exact information why which carcinogen in which drug causes which type of tumor. Otherwise, the FDA should not announce its detailed recommendations to drug manufacturers. The present patient was successfully treated surgically by a transposition adjacent flap. The optimal dermatosurgical and reconstructive methodologies for the treatment of tumors in the ala nasi area are discussed.

CONGENITAL LYMPHANGIOMA OF THE FOOT MIMICKING MULTIPLE VIRAL WARTS: DERMATOSURGICAL APPROACH WITH SECONDARY WOUND HEALING AND FAVOURABLE FINAL OUTCOME.

The problems with lymphangiomas in general stem from the fact that on the one hand they most often show an atypical clinical picture, and on the other hand their localization does not always allow the desired complete surgical removal. Lymphangiomas are rare and benign tumors of the lymphatic vessels. In the higher percentage of cases, they are defined as congenital malformations. The acquired type can manifest due to a variety of external factors, resulting in a benign distinct lesion, which can often be mistaken for another benign or malignant one. Although benign and even surgically treated , the recurrence rate is high. The pathogenesis of these tumours is unclear and is presumed to be due to an error in the fetal/embryonal development. Nosologically, these lesions belong to the group of so-called low flow lesions. Within the framework of their differentiation, it is important to distinguish them from hemangiomas and venous malformations, as although overlapping to some extent, at times- therapeutic options differ. This differentiation is most adequately accomplished by the application of MRI and Doppler, necessarily accompanied by histopathologic verification of the lesion. Spontaneous regression, although rare, occurs in up to 6% of cases. Surgical removal remains the safest method of treatment to date, and according to the literature this is possible in only 18 to 50% of cases. Often, however, the atypical clinical presentation of some of the lesions could be confusing for clinicians and could be the reason for prolonged and unsuccessful conservative or semi-invasive therapy. We present a 23-year-old patient with a history of complaints of more than 15 years in the form of itching, burning, and discomfort in the left foot area. The finding was treated under the diagnosis of viral warts with variable results and subsequent achievement of short-term remissions for no more than 5 -6 months. Due to an increase in pain symptomatology and an increase in the size of the lesion after the last cryotherapy, a skin biopsy was taken to confirm the diagnosis of lymphangioma. During hospitalization, the patient underwent MRI/Doppler of the vessels to determine the depth of infiltration and the presence/exclusion of communication to larger vascular formations for preoperative planning. Surgery was performed with secondary wound healing resulting in a favourable outcome.

SUBUNGUAL HEMATOMA OVERLAPPING WITH SUBUNGUAL LOCATED FOCAL MELANOCYTIC HYPERPLASIA: DERMATOSURGICAL APPROACH AS OPTIMAL TREATMENT CHOICE.

Subungual lesions present a serious challenge for clinicians. The following factors can cause certain problems in interpreting the data: 1) Changes in lesion morphology over time: It may indicate the presence of a malignant lesion (increased pigmentation over time and lack of distal growth) but may actually be a benign lesion (chronic persistent subungual hematoma). 2) Patient's medical history can be misleading or difficult to verify, especially in problematic patients, or those with mental health problems or communication disorders (e.g., Asperger's syndrome, autism, schizoid psychosis, etc.). 3) The morphology of the lesion itself can be difficult to determine in the presence of simultaneously overlapping lesions. These patient dilemmas primarily concern the differentiation between subungual hematomas from subungual melanomas. The clinicians's concerns are based on the potential for metastasis and the risk of significantly worse prognosis for patients affected by nail biopsy. We present a 19-year-old patient with a subungual pigmented lesion with a clinical/dermatoscopic suspicion for subungual melanoma. Primary complaints for about 3-4 months. Intensified pigmentation and increase in size within two months led to a partial surgical resection of the nail plate and nail bed, followed by adaptation of the wound edges with single interrupted sutures. The histopathological finding was indicative of a subungual hematoma located above a focal melanocytic hyperplasia of the nail bed, clear resection lines. After a literature review, we believe that this is the first case of a patient with simultaneously present subungual benign focal melanocytic hyperplasia overlapping with a chronic persistent subungual hematoma.

METATYPICAL BCCS OF THE NOSE TREATED SUCCESSFULLY VIA BILOBED TRANSPOSITION FLAP: NITROSAMINES IN ACES (ENALAPRIL), ARBS (LOSARTAN) AS POSSIBLE SKIN CANCER KEY TRIGGERING FACTOR.

The pathogenesis of keratinocytic skin cancer has been well-studied over the years, with a main focus on the influence of UV radiation and the subsequent changes in the genome regulator p53, which affects the cell cycle and the programmed cell death, apoptosis. Alarming and relatively new trend is the link between nitrosamines in blood pressure medications (but not only) and the development of both melanocytic and keratinocytic skin tumors. In the recent past, high concentrations (above the so-called daily acceptable intake dose) of nitrosamines in ACE inhibitors and sartans became the reason for some of these medications to be officially withdrawn from the drug market. As of now, and according to the lawsuits filed, contamination with even or just one nitrosamine could be the cause of lawsuits for between 5 to 10 forms of cancer overall. Single case reports, but also large-scale retrospective international studies, find a connection between the intake of possibly nitrosamine contaminated ACE inhibitors/sartans with the subsequent development of basal cell carcinomas. The same studies also found a serious risk of developing melanomas and squamous cell carcinomas after taking ACE inhibitors, thiazide diuretics and sartans. This, in turn, leads clinicians to ponder the following dilemma: Is it possible that the key pathogenetic link concerning the development of skin cancer is due to their radically different mechanism of action (ACEs/ARBs/Thiazides)? Or, more likely, in all three antihypertensive drug classes, such as sartans, ACE inhibitors, and thiazide diuretics, there is another cancer-causing contaminant, the so-called nitrosamines? Systemic intake of potentially nitrosamine-contaminated sartans and ACE inhibitors would logically lead to the generation of relatively uniform skin tumors. Proceeding precisely from this thesis, we present two non-related cases of metatypical basal cell carcinomas in the nasal area, which occurred during the administration of ACE inhibitors/angiotensin receptor blockers and were successfully treated by transpositional reconstructive flap - bilobed flap. Possible contamination with nitrosamines as a pathogenetically significant factor is discussed.

KARAPANDZIC FLAP FOR SQUAMOUS CELL CARCINOMA OF THE LOWER LIPP: POTENTIAL ROLE OF NITROSAMINES IN EPROSARTAN AS CANCER TRIGGERING FACTORS.

Chronic alcohol use, smoking, poor dental hygiene, absorbed sun radiation over the years, fair skin (Fitzpatrick type 1), light eyes, painful sunburns, congenital or acquired immunosuppression, certain rare syndromes, as well as infections with human papillomaviruses are perceived as risk factors for the development of squamous cell carcinoma of the lips. The new and at the same time modern aspects involving the pathogenesis of keratinocyte tumors in practice prove to be quite problematic for both patients and clinicians. These aspects are involved in the contamination or increased availability of certain nitrosamines in the antihypertensive medications. A serious international study in the last year has linked the intake of potentially contaminated (established availability without data on whether it exceeds the so-called ADI/acceptable daily intake dose) with nitrosamines valsartan with a relatively low, but still present risk of melanoma development. On the other hand, data from 2017 associate individual monotherapy of arterial hypertension with sartans with a significantly increased/statistically significant risk of squamous cell carcinomas development: more than a two-fold increased risk. It should be noted that at that time the problems with nitrosamines were completely unknown to the medical community. At the moment, there are numerous case studies that connect the use of sartans with the development of keratinocyte tumors - either single or multiple. We describe the first case of a patient who took eprosartan at a dose of 600 mg once a day for a total period of about 15 years with intake interruptions of no more than 6 years. Primary complaints in the lower lip area are from about 6 months. The preoperative biopsy showed evidence of squamous cell carcinoma. A multidisciplinary team performed a successful surgical treatment using the Karapandzic method, achieving an optimal aesthetic result. Based on the available literature data, the possible role of nitrosamines as a potential trigger for the development of squamous cell carcinoma is discussed.

[Mini-invasive approach in the treatment of acute necrotizing pancreatitis].

OBJECTIVES: The study aims to evaluate the efficacy of percutaneous necrosectomy performed under ultrasound control and endoscopic necrosectomy trough secondary sinus track (ENTSST) using nephroscope and cystoscope. MATERIAL AND METHOD: Puncture of fluid collections in the pancreas was performed under ultrasonographic control to 23 patients with acute necrotizing pancreatitis (ANP). ENTSST using nephroscope and cystoscope was performed to 47 patients after open or percutaneous necrosectomy and persistent sepsis (without satellite collection of CT). RESULTS: Seventeen (74%) patients treated with percutaneous necrosectomy recovered without open surgery. Two of this group died. The average hospital stay was 42 days. Twenty-three patients required an average of two (from 1 to 4) ENTSST. CONCLUSIONS: Based on our initial results we believe that the percutaneous necrosectomy and ENTSST in well selected patients might be the better choice than the open necrosectomy and postoperative lavage. Common solution of these methods has not been reached yet.

[Gunshot injuries of the ureters--retrospective study of 12 patients over 27 years period].

AIM: To retrospectively study the gunshot injuries of the ureters, operated in the surgical departments of Military Medical Academy, Sofia and Medical Institute Ministry of Interior, Sofia for a period of 27 years. MATERIAL AND METHOD: The gunshot injuries of the ureters of twelve patients are retrospectively studied in the period 1980 to 2007. For all patients the localization of the injuries, urinanalysis, imaging examination results, the associated injuries, the operative procedures and complications were reviewed. RESULTS: All patients are males aged 19-28 years. Seven patients have right ureteral injuries and five have left ureteral inuries. In three patients the urinanalysis is normal, five have microscopic and four have gross hematuria. The injury is located in the proximal third of the urether for six patients, in four it is in the mid and in another two in the the distal ureter. Complications are registered in 40% of the cases. CONCLUSIONS: Due to the high ratio of false negative results from the urinanalysis and the imaging studies, careful and precise exploration of the retroperitoneum in order no to omit a possible injury of the ureters.

[Intrathyroidal parathyroid adenoma and ectopic parathyroid gland in thyroid nodule - report of two cases].

Ectopic locations of parathyroid adenomas are a rare condition and can cause difficulty in their diagnosis and surgical treatment. We report two cases of intrathyroid parathyroid lesions. In the first patient, preoperative localization studies suggested the possibility of a parathyroid adenoma outside the thyroid gland. When a pathological gland is not found during surgery for primary hyperparathyroidism, an ectopic parathyroid gland was found in the thyroid tissue. In the second patient, in an existing thyroid nodule was found an ectopic normal parathyroid gland postoperatively.