Erika Kis

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.

Neglected Basal cell carcinomas in the 21st century.

Although tumors on the surface of the skin are considered to be easily recognizable, neglected advanced skin neoplasms are encountered even in the 21st century. There can be numerous causes of the delay in the diagnosis: fear of the diagnosis and the treatment, becoming accustomed to a slowly growing tumor, old age, a low social milieu, and an inadequate hygienic culture are among the factors leading some people not to seek medical advice. The treatment of such advanced neoplasms is usually challenging. The therapy of neglected cases demands an individual multidisciplinary approach and teamwork. Basal cell carcinoma (BCC), the most common cutaneous tumor, usually develops in the elderly, grows slowly, and has an extremely low metastatic potential; these factors are suggesting that BCCs might well be the “ideal candidates” for neglected tumors. Five neglected advanced cases of BCC were diagnosed in our dermatological institute between 2000 and 2009. The clinical characteristics and treatment modalities of these neoplasms are discussed, together with the possible causes of the neglect.

Guidelines for the use of biomarkers: Principles, processes and practical considerations

Abstract With the growing availability of new health care technologies and rapidly emerging biomarker discoveries, clinicians need advice on the clinical validity and utility of new tests and whether they improve clinical, patient-centred, organizational or economic outcomes. High quality clinical practice guidelines (CPGs), based on well-designed and conducted test evaluation studies, are tools for translating research into practice and in promoting a value- and evidence-based approach for clinical utilization and reimbursement of new biomarkers. Such study protocols should be appropriate for the questions addressed at each stage of biomarker development: 1/ Basic research into the association of disease with the new biomarker; 2/ Modelling the potential use of the new biomarker in clinical practice; Studies on the 3/ analytic validity; 4/ clinical validity (efficacy); 5/ clinical utility (effectiveness); and 6/ clinical impact (efficiency) of testing. Irrespective of the facts that CPGs potentially influence important clinical decisions and thus patient outcomes, current approaches to CPG development often do not follow the rigorous processes of scientific publications. Guidelines should be outcome oriented; reliable and free from any forms of bias; based on high quality research or on formal consensus when evidence is conflicting or lacking; multidisciplinary; flexible and applicable to various clinical circumstances and patient preferences; clear; cost-effective; appropriately disseminated and implemented; amenable to measurement of their impact in practice; and regularly reviewed and updated. Therefore until guideline-making and reporting standards are improved, all CPGs should be carefully scrutinized for methodological and content validity before being adopted, adapted and used in clinical practice.

Quality assessment of clinical practice guidelines for adaptation in burn injury

OBJECTIVES A number of clinical practice guidelines (CPGs) are available for managing burn injury patients but clinical practice is highly variable. We report the first steps to trans-contextual adaptation of international burn CPGs to local settings. METHODS Key clinical topics and questions to be covered in the final guideline were defined and prioritized. Systematic search between 1990 and 2008 retrieved 546 citations, of which 24 were CPGs on the general and intensive care of burn patients. Assessment of the clinical content of CPGs was carried out. Methodological quality of CPGs was evaluated using the AGREE instrument. RESULTS Of the 24 CPGs evaluated, 10 (42%) were evidence-based. All major burn topics were covered by at least one CPG, but no single CPG addressed all areas important in terms of outcomes. According to the AGREE criteria, 2 CPGs (8%) were strongly recommended, 14 with provisos or alterations (58%) and the rest were not recommended for adaptation. CONCLUSIONS Although existing CPGs for the management of burn may accurately reflect agreed clinical practice, most performed poorly when evaluated for methodological quality. Future CPG efforts addressing these methodological shortcomings would add substantially to the improved management of burned patients.

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

A novel missense mutation of the CYLD gene identified in a Hungarian family with Brooke–Spiegler syndrome

Brooke–Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant disease characterized by skin appendage tumors due to mutations in the cylindromatosis gene (CYLD). We investigated a Hungarian BSS pedigree with two affected members, father and daughter. Direct sequencing demonstrated a novel missense mutation (c.2613C>G; p.His871Gln) in exon 19 within the ubiquitin‐specific protease domain of the encoded protein. We performed preliminary analysis to reveal the functional role of this novel mutation. Our data suggest that this novel CYLD mutation leads to increased ubiquitination of NEMO through influencing deubiquitinating activity of the CYLD protein and thus may result in enhanced NF‐κB signalling.

Description of five dirofilariasis cases in South Hungary and review epidemiology of this disease for the country

SummaryBackgroundDirofilariasis is an emerging zoonosis (supported by climate change) in Central Europe. Human infections are usually caused by Dirofilaria repens and Dirofilaria immitis with mediation of mosquito vectors. Aims of this publication were to report our dirofilariasis cases, and to summarize Hungarian epidemiological data by reviewing literature.Methods and resultsWe present five (four ophthalomological, one subcutaneous) cases observed within a 2-year period in Southern Hungary. Ages of infected patients were between 31 and 74 years. First case during pregnancy is also reported. There was no travel history in the anamnesis of patients which could explain acquisition of the infection. Moving, intact worms eliminated by surgical interventions were identified on the basis of morphological features as D. repens. Since the first report of human case, 115 further episodes (in addition to ours) were diagnosed in Hungary. Mean age of the patients was 47 years. Reviewing national reports, the ratio of subcutaneous infections was higher than that of the ocular ones (66 and 45, respectively). Evaluation of the territorial distribution of human episodes revealed that most infections occurred in patients living in the Danube–Tisza interfluvial region and eastern part of the country. However, sporadic cases were also found in western counties during 2014.ConclusionMost of the Hungarian dirofilariasis cases were autochthonous infections. Occurrence in the western counties may suggest the spreading of this emerging zoonosis to these areas. Comprehensive monitoring and data analysis are desirable, therefore reporting the epidemiologic data in the case of human infections should be made mandatory.

Electrochemotherapy of melanoma cutaneous metastases

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.