The role of electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinoma: long-term results.

BACKGROUND: While electrochemotherapy (ECT) is increasingly utilized as a highly effective method in the treatment of tumors in the head and neck region, there is significantly less data available for eyelid-periocular skin tumors. Our group reported the first extensive case series of eyelid-periocular basal cell carcinoma (BCC) patients with short-term follow-up treatment with ECT. The present study aims to report our long-term results of eyelid-periocular BCC cases treated with ECT. METHODS: The treatments were performed according to the ESOPE (European Standard Operating Procedures on Electrochemotherapy) guidelines using the Cliniporator™ device. All patients received bleomycin-based ECT, administered intratumorally or intravenously. Tumor response was evaluated using the RECIST 1.1 criteria. RESULTS: The results of 19 patients treated with ECT are presented. Four patients had locally advanced primary tumors, while 15 patients had recurrent tumors. Bleomycin was administered intratumorally in four patients and intravenously in 15 patients. The overall response was 100%, while the complete response rate proved to be 95%. In three cases (15.8%), recurrence was observed during the mean follow-up period of 78.9 months. CONCLUSIONS: ECT can effectively treat locally advanced or recurrent BCC in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with long interval follow-up.

Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study.

We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P  = 0.0018, HR = 0.352) and OS ( P  = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P  = 0.0001, HR = 2.629; OS: P  = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.

[Electrochemotherapy for multiple cutaneous tumors in immunosuppressed patients]. / Immunszupprimált betegek multiplex bordaganatainak elektrokemoterápiás kezelése.

INTRODUCTION: The risk of cutaneous malignancies is significantly higher in immunosuppressed patients compared to the general population. These high-risk skin tumors tend to be aggressive, multiplex, rapidly growing lesions. It is common to see local recurrence after surgical excision. Multiplex tumors are difficult to treat, especially in the head/neck region. OBJECTIVE: Amongst the standard treatment options, electrochemotherapy can be a suitable option. Our aim was to evaluate the efficacy of electrochemotherapy in immunocompromised patients. METHOD: In 9 immunosuppressed patients, 118 (average: 13, n = 5-27) non-melanoma skin tumors were treated with electrochemotherapy with intravenous administration of bleomycin, according to the ESOPE criteria. RESULTS: The median follow-up was 15 months. 6 months after the treatment, the objective response rate was 96%. We observed complete response in 88%, partial response in 8% and progressive disease in 2% of the treated lesions. In 2%, the response was not evaluable. CONCLUSION: In immunocompromised patients, electrochemotherapy is an effective and safe therapeutic option for non-melanoma skin tumors. In order to provide more ideal management for this special sub-group, prevention, multidisciplinary approach and optimized immunosuppressive therapy is essential. Orv Hetil. 2023; 164(37): 1462-1468.

Innovation in the treatment of non-melanoma skin cancer: daylight photodynamic therapy / Új eljárás a nem melanoma típusú bordaganatok kezelésében: "daylight" fotodinámiás terápia

Introduction: Photodynamic therapy is indicated for the treatment of superficial basal cell carcinoma, Bowen's disease and actinic keratosis. Reactive oxygen radicals are released from the metabolite of the topically applied photosensitizer that is excited by light, which selectively leads to the destruction of tumor cells. The procedure can be performed with an artificial light source or with the use of sunlight. The latter is called daylight photodynamic therapy, which is an effective and painless procedure. Objective: Our aim was to introduce daylight photodynamic therapy in actinic keratoses at our department and to optimize the treatment protocol for the local climatic conditions. Method: Three clinical trials were performed. The difference between the treatment protocols was between the incubation time of the photosensitizer on the skin and in the time patients spent under the sunlight. Results: When using the international treatment protocol, 73% of the actinic keratoses showed complete, while 27% partial remission. By reducing the proportion of time patients spent outdoor, complete remission was achieved in

Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial.

Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of Szeged, Hungary. During this once only treatment up to ten measurable cutaneous metastases per patient were separately block randomized for intratumoral delivery of either calcium or bleomycin, which was followed by reversible electroporation. Tumour response was evaluated clinically and histologically six months after treatment. (ClinicalTrials.gov: NCT03628417, closed). Seven patients with 44 metastases (34 from malignant melanoma, 10 from breast cancer) were included in the study. Eleven metastases were taken for biopsies, and 33 metastases were randomised and treated once. The objective response rates were 33% (6/18) for Ca-EP and 53% (8/15) for bleomycin-based ECT, with 22% (4/18) and 40% (6/15) complete response rates, respectively. The CR was confirmed histologically in both arms. Serious adverse events were not registered. Ulceration and hyperpigmentation, both CTCA criteria grade I side effects, were observed more frequently after bleomycin-based ECT than for Ca-EP. Ca-EP was non-inferior to ECT, therefore, it should be considered as a feasible, effective and safe treatment option.

Electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinomas.

There is increasing evidence about the effectiveness of electrochemotherapy (ECT) in the treatment of basal cell carcinomas in the head and neck region, although its role in the management of eyelid-periocular skin tumors has to be clarified. The aim of the present study is to evaluate the results of ECT in the treatment of locally advanced primary and recurrent eyelid-periocular skin basal cell carcinomas. Twelve patients with basal cell carcinoma involving the eyelid-periocular skin region were treated with ECT. Three patients had locally advanced primary tumors, while 9 patients had recurrent tumors. All treatments were performed according to the ESOPE guidelines, using Cliniporator TM device. All patients received bleomycin based ECT. The route of administration was intratumoral in 3 patients and intravenous in 9 patients. Tumor response was evaluated using the RECIST 1.1. criteria. ECT resulted in complete response of the periocular skin tumors in all patients. Lower eyelid ectropion was developed in 3 patients which had to be corrected surgically. ECT can be used effectively in the treatment of locally advanced or recurrent basal cell carcinomas in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with short interval follow-up.

[Factors influencing early detection of malignant melanoma]. / A melanoma malignum korai felismerését befolyásoló tényezok.

INTRODUCTION AND AIM: Melanoma is a highly aggressive tumour with often unpredictable outcome. Our aim with this study was to determine factors influencing early detection of melanoma. METHOD: We analyzed 139 questionnaires completed by patients diagnosed with melanoma. RESULTS: We found that our patients are health-conscious regarding cardiovascular diseases and attend cancer screenings on recall. However, their knowledge about melanoma is insufficient. Most of them perform skin self-examination, but they do not know what to check. Melanoma is detected mostly by the patients themselves, but it takes more than one year to consult a doctor. Our study confirmed that patients' attitude toward melanoma is an important factor influencing early detection. We found that physical examination and communication about skin cancer prevention is not part of the routine medical care. CONCLUSIONS: It is important to improve knowledge about melanoma among the general population and health care providers and to emphasize that early detection can save lives. Orv. Hetil., 2016, 157(51), 2028-2033.

A randomised trial to demonstrate the effectiveness of electronic messages on sun protection behaviours.

Message exposure is effective at changing a variety of health behaviours. Our aim was to improve sun protection habits of a volunteer sample. We conducted a randomised, non-blinded, investigator-initiated trial (from 1st June to 31st August in 2011) on the effect of an electronic text-message system on sun protection behaviours. The assessments of 149 healthy volunteer participants took place at the Clinical Department of Dermatology and Allergology at the University of Szeged in Hungary. Psychological and medical assessments were also made. Total motivation scores for adherence to sunscreen use improved at a nearly significant level (t=-1.954, p=0.054). The intervention group used sunscreens more often than the other groups according to their sun exposure diaries (F=8.173, p<0.05) and their interview results (F=3.44, p<0.05). Using electronic messages offers an effective method to improve sun protection behaviours. Our intervention is a cost-effective method and it can easily be implemented at worksites.

Neonatal blue light phototherapy and melanocytic nevi: a twin study.

BACKGROUND: Neonatal blue light phototherapy (NBLP) has been widely and successfully used for the treatment of neonatal jaundice to reduce the plasma concentration of bilirubin and, hence, to prevent kernicterus. Only a few and controversial data are available in the literature as to how NBLP influences melanocytic nevus development. OBJECTIVE: Our goal was to conduct a twin study with the aim of better understanding the role of NBLP in melanocytic nevus development. We also investigated the roles of other environmental and constitutional factors in nevus formation. METHODS: Fifty-nine monozygotic and dizygotic twins were included in this cross-sectional study. One of the twin members received NBLP, and the other did not. A whole-body skin examination was performed to determine the density of melanocytic skin lesions. The prevalence of benign pigmented uveal lesions was evaluated during a detailed ophthalmologic examination. A standardized questionnaire was used to assess data relating to constitutional, sun-exposure, and other variables. To search for possible gene-environmental interactions involved in the appearance of pigmented lesions, the melanocortin 1 receptor variants and the I439V polymorphism of histidine ammonia-lyase genes were also determined in the enrolled twins. RESULTS: NBLP was associated with a significantly higher prevalence of both cutaneous and uveal melanocytic lesions. No association was found between the examined gene polymorphisms and the number of pigmented alterations in the examined study group. CONCLUSIONS: Our data suggest that NBLP could well be a risk factor for melanocytic nevus development. Phototherapy with blue-light lamps is a standard and essential therapeutic modality in neonatal care; therefore, additional in vivo and in vitro studies are necessary to establish its potential long-term adverse effects.

[Extravasation of cytostatic drugs]. / Citosztatikumok paravazációja.

Paravasation of cytostatic drugs during peripheral intravenous administration is a well known complication. In the United States of America it occurs in seven percent of cases with different severity and consequences. Although methods to completely avoid this complication are still unavailable, we are able to decrease the risks by identifying the patient- and procedure-related factors. The educated patient is a good indicator of paravasation in case he or she can cooperate and call the nurse. When the patient is unable to cooperate, the risks of extravasation is higher and closer nursing surveillance is indicated. The extent of injury depends mainly on the chemical structure of the extravasant substance (vesicant, irritant or non-vesicant) which may be modified by other factors. There is no strong evidence-based guidance for the management of complication. Abrupt cessation of the infusion and drawing back on the inserted venous catheter as well as elevating and resting the affected limb are necessary measures. In the available literature cooling or warming of the affected area is controversial. Similarly there are still open questions regarding the value of using antidotes as dexrazoxane, dimethylsulfoxide, thiosulfate and hyaluronidase (which is not registered as medicament in Hungary). In the event of extravasation early multidisciplinary dermatological and surgical assessment is essential for definitive diagnosis and setting the optimal management.

Electrochemotherapy of cutaneous metastases of melanoma--a case series study and systematic review of the evidence.

OBJECTIVES: Electrochemotherapy (ECT) is a novel therapeutic option for the treatment of cutaneous and subcutaneous metastases of malignant melanoma. During the treatment, electric pulses are applied to tumor nodules to deliver nonpermeant or poorly permeant chemotherapeutic agents into the cells, increasing local cytotoxicity of anticancer drugs. We compared the clinical effectiveness of ECT as an alternative palliative treatment option for unresectable metastatic lesions of malignant melanoma with a systematic review of reported outcomes. METHODS: One hundred fifty-eight cutaneous and subcutaneous metastases of nine patients were treated with ECT. All treatments were performed under general anesthesia using intravenous bleomycin injection. Median follow-up was 195 days. RESULTS: In our case series, complete response rate was 23%, and partial response rate was 39%. We observed no change in 30% and progressive disease in 8% of cases. CONCLUSIONS: ECT is a simple and effective treatment of single or multiple cutaneous and subcutaneous metastases of melanoma with minimal side effects. Our results provide further data for the growing body of evidence in recently published studies that ECT used for palliation has clinical benefit. The authors have indicated no significant interest with commercial supporters.

[Electrochemotherapy of melanoma cutaneous metastases]. / Melanoma-bôráttétek elektrokemoterápiája.

UNLABELLED: Electrochemotherapy is an effective treatment of cutaneous and subcutaneous metastases in patients with malignant melanoma. During the treatment, electric pulses are applied to tumor nodules to deliver non-permeating or poorly permeating chemotherapeutic agents into the cells thereby increasing local cytotoxicity of anticancer drugs. METHODS: In 7 patients 81 cutaneous and subcutaneous melanoma metastases were treated with electrochemotherapy. All treatments were performed under general anesthesia using intravenous bleomycin injection. Median follow-up was 218 days. RESULTS: Complete response rate was 25%, partial response rate was 43%. We observed no change in 26%, and progressive disease in 6%. CONCLUSIONS: Electrochemotherapy is a simple and effective treatment of single or multiple cutaneous and subcutaneous metastases of melanoma, with minimal side effects. Our results confirm the results of recently published studies that the treatment used for palliation has clinical benefit and impact on the quality of life.

Hematoma-like metastasis in melanoma.

Three years after removal of a primary tumor, spontaneous hematoma developed on the anterior aspect of the chest of a 33-year-old woman. Ultrasound examination verified by histologic findings indicated subcutaneous metastasis. This new type of metastasis with characteristic clinical features has not been mentioned in the literature, and we named it "hematoma-like metastasis." Special care should be taken in examining patients with melanoma and spontaneous hematoma.

Pemphigus vegetans presenting as acrodermatitis continua suppurativa.

The authors present a 51-year-old patient with clinical signs of acrodermatitis continua suppurativa of the toes. Since histological findings failed to unambiguously support the diagnosis of acrodermatitis continua suppurativa, immunohistology was performed. The results showed intercellular epidermal fluorescence. The subsequent clinical picture (vegetating formation), the repeated histological examination (suprabasal cleft and eosinophilia), as well as the data of immunohistological findings supported the diagnosis of pemphigus vegetans Hallopeau. The patient was treated successfully with a combination of cyclosporine-A and low-dose steroid therapy. The case is of special interest, because there is only a single publication about phalangeal and nail involvement in Hallopeau's type pemphigus vegetans in the dermatological literature according to our knowledge.

[The role of PET scan in the diagnosis of malignant melanoma]. / A PET jelentósége a melanoma malignum diagnosztikájában.

Comprehensive, accurate staging has a critical role in planning rational treatment strategies for patients with malignant melanoma (MM). In the present study the authors investigate the value of FDG PET in staging and restaging based on the investigation of 37 high-risk MM patients and compare the results with the one obtained by conventional imaging techniques (X-ray, US, CT, MR and bone scan). Thirty-nine whole body PET scans were carried out. The authors concluded that FDG PET had the highest sensitivity among the imaging methods in detecting distant metastases of MM.