Definition of novel electrochemotherapy parameters and validation of their in vitro and in vivo effectiveness.

Electrochemotherapy (ECT) is a cancer therapy that conjugates the administration of a chemotherapy agent to the delivery of permeabilizing pulses released singularly or as bursts. This approach results in higher number of anticancer molecules delivered to their biological targets, but is also associated to undesirable side effects such as pain and muscular contractions. A new electroporator delivering train of eight biphasic pulses at the voltage of 1,300 V/cm lasting 50 + 50 µsec each, with a frequency of 1 Hz, and with 10-µsec interpulse intervals (total treatment time: 870 µsec/cm(2) of treated area) was tested in vitro on the human lung cancer cell line A549 and in vivo, both in mice xenografts and privately owned rabbits with spontaneous tumors. The tumor cell line was treated with electroporation using the new parameters, that showed improved drug efficacy in causing cell death. Mice with chemoresistant xenografts were treated as well with either the new parameters and with a previous protocol, confirming the higher tolerability and efficacy of the novel parameters. Finally, a cohort of six pet rabbits with advanced skin neoplasms were enrolled in a compassionate trial using the new parameters in adjuvant fashion. In terms of efficacy, none of the rabbits experienced tumor recurrence, showing minimal discomfort during the ECT sessions. The data described, demonstrate that the new permeabilizing protocol adopting biphasic electric pulses displays a significant higher efficacy compared to previous ECT treatments and substantial reduction of the associated morbidity.

[Cutaneous and subcutaneous leiomyosarcoma: report of two cases]. / Leiomiosarcoma cutáneo y subcutáneo: reporte de dos casos.

Cutaneous leiomyosarcomas are uncommon malignant tumors of smooth muscle. We report herein two cases of cutaneous leiomyosarcoma, one of dermal and other of subcutaneous vascular origin, confirmed by histology and immunohistochemistry. Both cases were treated with wide surgical excision, one with local recurrence. No metastases were detected at follow-up. Leiomyosarcomas should be considered in lesions with histologic features of spindle cell malignancy. It is necessary in most of the cases a histological differentiation with specific immunohistochemical markers. The treatment of choice is radical excision with wide margins, achieving satisfactory results.

High Frequency Ultrasound of Basal Cell Carcinomas: Ultrasonographic Features and Histological Subtypes, a Retrospective Study of 100 Tumors.

(1) Background: 22 MHz high frequency ultrasound (HFUS) is a non-invasive imaging technique that gives information on depth, length, volume and shape of skin tumors. (2) Methods: We reviewed the clinical, ultrasound, and histological records of 54 patients with 100 histologically confirmed basal cell carcinoma (BCC) tumors with the use of HFUS. (3) Results: Most infiltrative tumors (n = 16/21, 76.2%) were irregular shaped, followed by five (23.8%) being round shaped; most superficial tumors (n = 25/29, 86.2%) were ribbon shaped, followed by four (13.8%) being round shaped; most nodular tumors (n = 26/33, 78.8%) were round shaped, followed by seven (21.2%) that were irregular shaped; and, lastly, all microdular tumors (n = 2/2, 100%) were round shaped. Strong evidence of association (p = 0.000) was observed between the histological subtype and tumor shape as seen using the HFUS. No evidence of association was found between the histological subtype and tumor margin (p > 0.005). Cohen's Kappa statistic to assess the agreement between BCC subtypes evaluated by histological examination and U/S appearance was calculated equal to 0.8251 (almost perfect agreement). (4) Conclusions: HFUS appears to be a reliable technique for the pre-operative evaluation of BCCs, assisting physicians to decide on the optimal therapeutic approach.

Shared decision-making quality and decisional regret in patients with low-risk superficial basal cell carcinoma: A prospective, multicenter cohort study.

Background: Many therapies are available to treat low-risk superficial basal cell carcinoma (lr-sBCC), which may complicate the shared decision-making (SDM) process. Objective: To assess the SDM process of patients and physicians when deciding lr-sBCC therapy as well as the factors that may influence the SDM process. Methods: A prospective, multicenter cohort study was conducted over 18 months, from October 2018 to April 2020, in 3 tertiary university hospitals and 1 private hospital. Results: This study included 107 patients. There was a weak positive correlation between Shared Decision-Making Questionnaire-Patient version (SDM-Q-9) and Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) (Spearman's correlation coefficient [rs] [105] = 0.21; P = .03). Most patients (71%) chose a nonsurgical treatment after the SDM process. Patients with higher satisfaction with the SDM had lower decisional conflict and decisional regret (P < .001). Patients aged >80 years had higher rates of significant decisional conflict. When evaluating treatment decisions, the highest median score for decisional conflict (22, IQR [16]; P = .01) was observed among patients who chose a surgical excision. Limitations: Patients may have self-selected to participate. Conclusion: This study suggests that some patients may prefer less invasive therapies for lr-sBCC. The SDM process may reduce decisional conflict and decisional regret.

Melanoma-specific survival is worse in the elderly: a multicentric cohort study.

We aimed to characterise cutaneous melanoma in the elderly and determine its association with poorer prognosis. We studied a prospective cohort of the melanoma population in Catalonia between 2012 and 2016. We compared young patient group (<75 years old) with elderly patient group (≥75 years old). We included 3009 patients (52.5% women) from 14 centres, with a mean age at diagnosis of 61.1 years. In the ≥75-year-old group there was a predominance of men (53.9% vs. 45.5%, P  < 0.001), melanoma was more frequently located in the head and neck area (37.7% vs. 15.5%, P  < 0.001) and lentigo maligna melanoma subtype was significantly more frequent (31.4% vs. 11.6%, P  < 0.001), as were nodular melanoma and acral lentiginous melanoma ( P  < 0.001). In older people, Breslow index, the presence of ulceration and mitotic rate were higher than in younger people. Kaplan-Meier survival curves showed longer melanoma-specific survival (MSS) and melanoma-free survival (MFS) in <75-year-old group compared to the elderly group. Cox regression models demonstrated reduced MSS in patients ≥75 years regardless of gender, location, IB, ulceration and lymph node status at diagnosis (HR 1.54, P  = 0.013) whereas MFS was not independently associated with elderly when head and neck location was considered. Age appears to be an independent risk factor for MSS but not for MFS. Worse melanoma prognosis in elderly could be explained by factors unrelated to the tumour, such as age-related frailty and comorbidities that limit the access to systemic treatments and, eventually, age-related immune dysfunction.

Clinical Images in Dermatology Manuscripts - A Study of Journal Submission Guidelines.

Background: Images are an important element of any scientific publication, more so for a very visual specialty such as dermatology. Dermatology journals generally include detailed instructions related to images submitted with the manuscripts, including technical aspects such as file format, resolution, and editing. We aimed to review and critically analyze instructions for images in the top 50 dermatology journals [as per the latest Clarivate journal citation report (JCR) ranking]. Methods: The top 50 journals as per the latest Clarivate JCR were included in the study. Instructions for images were reviewed for each of the journals. The main points analyzed included file type, resolution, size limits, editing limits, support for post-processing of images and details regarding patient consent. Results: Only half the journals (25) had clear, detailed, and specific instructions for the images. Only one journal specifically mentioned pixels per inch (PPI) as the descriptive term, and the remaining used dots per inch (DPI), whereas 6 did not mention either. Twenty-three journals did not mention the recommended size of the image. The most common minimum resolution mentioned was 300 DPI (41 journals). Although 24 of the journals mentioned editing limits, none of the journals elaborated on image plagiarism in the instructions. Twenty-one of the fifty did not mention a clear policy on patient consent. Conclusions: Image submission guidelines for dermatology journals need to be made more elaborate yet easier to understand. Developing a consensus, followed by standardization of these submission guidelines, can help both authors and journals.

Overview of germline and somatic genetic alterations in basal and squamous cell carcinoma: a review of the current literature.

Non-melanoma skin cancers (NMSCs), including basal and squamous cell carcinomas, represent the most common malignancies among Caucasians. Over two million cases of NMSC occur each year in the US, with a progressive increase in incidence. There are well-known environmental risk factors, such as iatrogenic or ionizing radiation exposure, but the effect of chronic ultraviolet radiation, especially ultraviolet B radiation, is one of the main predisposing factors. Currently, based on our knowledge of the pathophysiology of most NMSCs, we have a better understanding of the associated genetic risk factors. The aim of this study was to evaluate the factors that contribute to the onset of NMSC through a comprehensive literature research.

In Vivo Reflectance Confocal Microscopy as a Response Monitoring Tool for Actinic Keratoses Undergoing Cryotherapy and Photodynamic Therapy.

Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7-28.1), hyperkeratosis (OR: 13.6, CI: 5.3-34.9), stratum corneum disruption (OR: 7.8, CI: 3.5-17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9-14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

A dermatologist's peek at emigration and professionalism: Looking at the stream from the inside.

Much can be read on migration of health workers, on the impact of immigrations on the receiving countries, and on professional insertion in new labor markets. The terms to search are many: "reinsertion," "professionalism," "migration flow," "readjustment," and "immigrant qualified professionals." When asked to narrow it down to personal experience, one needs to reduce many of this complex and faceless processes to a more intimate view. Other terms come into mind: "self-esteem," "resilience," "nostalgia," "renaissance," "mimesis," and "catharsis." A special focus is placed on the Venezuelan diaspora, as a recent global migration group who has left the country, leaving behind a scarce 60% task force of formally trained physicians, a trend that continues today.

Use of Cytology in the Diagnosis of Basal Cell Carcinoma Subtypes.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the white population. Nonsurgical treatments are first-line alternatives in superficial BCC (sBCC); therefore, differentiating between sBCC and non-sBCC is of major relevance for the clinician. Scraping cytology possesses several advantages, such as an earlier diagnosis and scarring absence, in comparison to a biopsy. Nevertheless, previous studies reported difficulties in differentiating the different BCC subtypes. The objective of this study was to determine the capability and accuracy of scraping cytology to differentiate between sBCC and non-sBCC. METHODS: In this retrospective study, cytological samples of histologically confirmed BCC were examined. Select cytological features were correlated to BCC subtypes (sBCC or non-sBCC). RESULTS: A total of 84 BCC samples were included (29 sBCC; 55 non-sBCC). An inverse correlation between the diagnosis of sBCC and the presence of mucin, dehiscence, and grade of atypia in the basal cells was observed. The presence of medium and large basal cell clusters correlated directly to a sBCC diagnosis. The presence of clear cells is strongly associated with sBCC. Therefore, Conclusion: Scraping cytology is reliable in differentiating sBCC from other BCC subtypes.

Teledermatology and its Current Perspective.

Teledermatology is one of the most important and commonly employed subsets of telemedicine, a special alternative to face-to-face (FTF) doctor--patient consultation that refers to the use of electronic telecommunication tools to facilitate the provision of healthcare between the "seeker" and "provider." It is used for consultation, education, second opinion, and monitoring medical conditions. This article will review basic concepts, the integration of noninvasive imaging technique images, artificial intelligence, and the current ethical and legal issues.

Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study.

The incidence of melanoma has been increasing worldwide during recent decades. The objective of the study was to analyse the trends in incidence for in situ and invasive melanoma in the Spanish region of Catalonia during the period of 2008-2017. We designed a cross-sectional study with an age-period-cohort analysis of melanoma patient data from the Network of Melanoma Centres in Catalonia. Our database covered a population of over seven million and included a total of 8626 patients with incident melanoma. The main outcome measures were crude and age-standardised incidence rates to the European 2013 standard population. Joinpoint regression models were used to evaluate the population trends. We observed an increase in the age-standardised incidence rate (per 100,000 population) of all melanoma subtypes from 11.56 in 2008 to 13.78 in 2017 with an average annual percent change (AAPC) of 3.5%. This incidence increase was seen exclusively in the older population. Moreover, the stratified analysis showed a statistically significant increase in the age-standardised incidence rate for invasive (AAPC 2.1%) and in situ melanoma (AAPC 6.5%). In conclusion, the incidence of melanoma has continued to increase in the elderly population over recent decades, with a rapidly increasing trend of in situ melanomas and the lentigo maligna subtype.

In-vivo assessment of a case of cutaneous sarcoidosis using reflectance confocal microscopy.

Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that allows visualization of the epidermis and papillary dermis with cellular-level resolution. Granulomatous reactions such as sarcoidosis could be assessed using RCM. The identification of bright beaded-like structures that could correspond to reticulin fibers overlying granulomas, in association with dermoscopy, may be a very useful approach in the diagnosis of sarcoidosis and for the differentiation of this granulomatous entity with superficial cutaneous metastasis.