Role of imaging in the applicability of irreversible electroporation for the management of pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms, with a one-year survival rate below 20%. Axial methods (computed tomography and magnetic resonance imaging) play a fundamental role in the diagnosis and staging of the disease, because they provide adequate anatomical resolution in the assessment of key structures, mainly vascular structures. Pancreatic ductal adenocarcinoma is most often discovered in advanced stages, when surgical resection is no longer feasible. In that scenario, minimally invasive treatment alternatives have been developed in attempts to change the natural history of the disease. Irreversible electroporation, an interventional procedure that minimizes deleterious effects on adjacent tissues, has proven useful for the treatment of tumors traditionally considered unresectable. Despite the growing acknowledgment of this technique as a tool for the management of pancreatic ductal adenocarcinoma, it is still relatively unknown among radiologists. In this study, we sought to provide an overview of the main characteristics and eligibility criteria that must be considered for the indication of irreversible electroporation in cases of pancreatic ductal adenocarcinoma.

O adenocarcinoma ductal de pâncreas é uma das neoplasias malignas mais agressivas, com taxas de sobrevivência anuais inferiores a 20%. Os métodos axiais (tomografia computadorizada e ressonância magnética) têm papel fundamental no diagnóstico e estadiamento da doença, por fornecerem adequada resolução anatômica na avaliação de estruturas-chave, principalmente vasculares. O adenocarcinoma ductal de pâncreas é frequentemente descoberto em estágios avançados e sem viabilidade de ressecção cirúrgica, e nesse cenário o desenvolvimento de alternativas terapêuticas minimamente invasivas tem sido ainda mais importante para a mudança de sua história natural. A eletroporação irreversível, procedimento intervencionista que minimiza efeitos deletérios nos tecidos adjacentes, vem se destacando no tratamento de lesões tradicionalmente consideradas irressecáveis. Essa técnica, apesar de ganhar cada vez mais espaço no manejo terapêutico do adenocarcinoma ductal de pâncreas, ainda é pouco familiar aos radiologistas. Neste estudo, buscamos expor, de forma sucinta e didática, os fundamentos da técnica, as principais características de imagem e os critérios de elegibilidade que devem ser considerados para indicação da eletroporação irreversível nessa doença.

Communication in radiology: evaluation of terminology and TNM descriptor use at a cancer center.

Objective: The purpose of our study was to evaluate the transmission of information from radiologists to physicians, focusing on the level of certainty and the use of imaging descriptors from the tumor-node-metastasis (TNM) staging system. Materials and Methods: Radiologists (n = 56) and referring physicians (n = 50) participated in this questionnaire-based, singlecenter study, conducted between March 20, 2020, and January 21, 2021. Participants were presented with terms commonly used by the radiologists at the institution and were asked to order them hierarchically in terms of the level of certainty they communicate regarding a diagnosis, using a scale ranging from 1 (most contrary to) to 10 (most favoring). They then assessed TNM system descriptors and their interpretation. Student's t-tests and the kappa statistic were used in order to compare the rankings of the terms of certainty. Items related to T and N staging were analyzed by Fisher's exact test. The confidence level was set to 97% (p < 0.03). Results: Although overall agreement among the radiologists and referring physicians on term ranking was poor (kappa = 0.10- 0.35), the mean and median values for the two groups were similar. Most of the radiologists and referring physicians (67% and 86%, respectively) approved of the proposal to establish a standard lexicon. Such a lexicon, based on the participant responses, was developed and graphically represented. Regarding the TNM system descriptors, there were significant differences between the two groups in the reporting of lymph node numbers, of features indicating capsular rupture, and of vessel wall irregularities, as well as in the preference for clear descriptions of vascular involvement. Conclusion: Our findings indicate that ineffective communication and differences in report interpretation between radiologists and referring physicians are still prevalent in the fields of radiology and oncology. Efforts to gain a better understanding of those impediments might improve the objectivity of reporting and the quality of care.

Objetivo: O propósito do nosso estudo foi analisar a transmissão das informações de radiologistas para médicos assistentes, com foco no nível de certeza e uso de descritores de imagem do sistema de estadiamento tumor­nódulo­metástase (TNM). Materiais e Métodos: Radiologistas (n = 56) e médicos assistentes (n = 50) participaram neste estudo unicêntrico, baseado em questionários respondidos entre 20 de março de 2020 e 21 de janeiro de 2021. Os participantes ordenaram hierarquicamente termos comumente usados por radiologistas da instituição para descrever o nível de certeza utilizando uma escala que variou de 1 (mais contrário) a 10 (mais favorável). Em seguida, foram avaliados os descritores relacionados ao sistema TNM e sua interpretação. O teste t de Student e o coeficiente de correlação kappa foram empregados para comparar a classificação dos termos. Os itens relacionados aos estadiamentos T e N foram analisados pelo teste exato de Fisher. O nível de confiança foi fixado em 97% (p < 0,03). Resultados: A concordância geral entre radiologistas e médicos assistentes na classificação hierárquica dos termos foi baixa (kappa = 0,10­0,35), porém, os valores médios e medianos dos dois grupos foram semelhantes. A maioria dos médicos (86%) e radiologistas (67%) foi receptiva à introdução de um léxico padronizado. Uma proposta de léxico foi elaborada com base nas respostas dos participantes e representada graficamente. Em relação aos descritores do sistema TNM, diferenças estatisticamente significativas foram observadas nos seguintes itens: forma de relatar o número de linfonodos; menção a características indicativas de ruptura capsular nodal; menção de irregularidades nas paredes vasculares; e preferência por descrições sucintas para comprometimento de estruturas vasculares. Conclusão: Falhas de comunicação e diferenças na interpretação de laudos entre radiologistas e médicos assistentes ainda são prevalentes em radiologia e oncologia. Esforços para melhor compreendê-los podem melhorar a objetividade do laudo radiológico e a qualidade do atendimento médico.

Clonostachys rosea: Production by Submerged Culture and Bioactivity Against Sclerotinia sclerotiorum and Bemisia tabaci.

Among the prospective biocontrol agents, the saprophytic filamentous fungus Clonostachys rosea is an excellent necrotrophic mycoparasite of numerous plant pathogenic fungi. However, its commercial development has been hampered by mass production difficulties during solid-state fermentation. Conversely, the submerged liquid fermentation shortens the cultivation time while increasing yields of fungal propagules. However, this method has been overlooked for C. rosea. In this work, we investigated the impact of liquid pre-culture inoculum on the spore production by the two-stage fermentation process using rice grains in comparison to the traditional solid-state fermentation. In parallel, we studied the submerged cultivation of C. rosea by manipulating carbon-to-nitrogen (C:N) ratio and nitrogen source, with the further optimization of spore production in a benchtop bioreactor. Additional bioassays included assessing the bioactivity of water-dispersible microgranules (that contained a submerged conidia) against the whitefly (Bemisia tabaci biotype B) and Sclerotinia sclerotiorum (causal agent of the white mold). Our results showed a maximum concentration of 1.1 × 109 conidia/g-dry-matter after 7 days of cultivation by two-stage fermentation process. The liquid fermentation yielded 1.4 × 109 submerged conidia/ml after 7 days using a medium with a 50:1 C:N ratio, and it also induced the production of microsclerotia (MS) up to 1.35 × 104/ml within 6 days with 10:1 C:N ratio; both media were supplemented with dextrose monohydrate and soybean meal. The fermentation batches carried out in a benchtop bioreactor with medium 50:1 C:N ratio and amended with soybean meal rendered a production peak on the fourth day, corresponding to 1.11 × 109 conidia/ml and 4.35 × 108 colony forming units (CFU)/ml. Following air-drying, the conidia production from air-dried microgranules of C. rosea biomass was estimated at 3.4 × 1010 conidia/g of formulated product upon re-hydration for 7 days. Both submerged conidia and MS of C. rosea inhibited 100% germination of S. sclerotiorum sclerotia by direct parasitism. The air-dried submerged conidia exhibited a suppressive activity on sclerotia (88% mycoparasitism) and early whitefly nymphs (76.2% mortality) that rendered LC50 values of 3.2 × 104 CFU/g soil and 1.5 × 107 CFU/ml, respectively. Therefore, the submerged liquid culture of C. rosea may offer a feasible and cost-effective method for its large-scale production, alleviating critical constraints to their commercial use while providing an additional tool for management of B. tabaci and S. sclerotiorum.

Factors associated with subcentimeter pulmonary nodule outcomes followed with computed tomography imaging in oncology patients.

INTRODUCTION: Technological advancements in computed tomography (CT) have enabled the frequent detection of small pulmonary nodules (PNs), especially in patients with an oncologic history. It is important the malignant versus benign etiology of PNs be determined. The aim of the present study was to evaluate the behavior and clinical/radiological characteristics of subcentimeter PNs detected by CT in oncologic patients. METHODS: An observational, longitudinal, retrospective and single-center study was conducted with a sample of 100 patients with a diagnosis of a primary malignant solid tumor outside of the lungs who developed indeterminate subcentimeter PNs (n = 251) detected on consecutive thoracic CT scans from 2015 to 2017. Follow-up CTs for each patients were examined in each of three periods (0-3 months, 3-6 months, and 6 months to 1 year). RESULTS: In our study sample, 28 patients (28 %) showed one or more signs suspicious of pulmonary metastasis, including ≥50 % PN growth, nodule growth followed by size reduction in patients undergoing chemotherapy, and the appearance of multiple nodules. The majority (56 %) of the PNs were detected during the 3-6-month follow-up CT scan. PNs with irregular, lobuled, or spiculated margins exhibited faster growth than PNs with regular, smooth margins. Malignancy of PNs was found to be significantly associated with being male, a primary colorectal cancer diagnosis, and advanced stage disease. CONCLUSION: Our findings reinforce the necessity of an individualized CT follow-up strategy for patients with an oncologic history, as well as the importance of early nodule screening, with the inter-scan interval being dependent on the primary neoplasm.

Improved anti-Cutibacterium acnes activity of tea tree oil-loaded chitosan-poly(ε-caprolactone) core-shell nanocapsules.

The purpose of this study was to develop tea tree oil (TTO)-loaded chitosan-poly(ε-caprolactone) core-shell nanocapsules (NC-TTO-Ch) aiming the topical acne treatment. TTO was analyzed by gas chromatography-mass spectrometry, and nanocapsules were characterized regarding mean particle size (Z-average), polydispersity index (PdI), zeta potential (ZP), pH, entrapment efficiency (EE), morphology by Atomic Force Microscopy (AFM), and anti-Cutibacterium acnes activity. The main constituents of TTO were terpinen-4-ol (37.11 %), γ-terpinene (16.32 %), α-terpinene (8.19 %), ρ-cimene (6.56 %), and α-terpineol (6.07 %). NC-TTO-Ch presented Z-average of 268.0 ± 3.8 nm and monodisperse size distribution (PdI < 0.3). After coating the nanocapsules with chitosan, we observed an inversion in ZP to a positive value (+31.0 ± 1.8 mV). This finding may indicate the presence of chitosan on the nanocapsules' surface, which was corroborated by the AFM images. In addition, NC-TTO-Ch showed a slightly acidic pH (∼5.0), compatible with topical application. The EE, based on Terpinen-4-ol concentration, was approximately 95 %. This data suggests the nanocapsules' ability to reduce the TTO volatilization. Furthermore, NC-TTO-Ch showed significant anti-C. acnes activity, with a 4× reduction in the minimum inhibitory concentration, compared to TTO and a decrease in C. acnes cell viability, with an increase in the percentage of dead cells (17 %) compared to growth control (6.6 %) and TTO (9.7 %). Therefore, chitosan-poly(ε-caprolactone) core-shell nanocapsules are a promising tool for TTO delivery, aiming at the activity against C. acnes for the topical acne treatment.

Development and in vivo evaluation of chitosan-gel containing Mitracarpus frigidus methanolic extract for vulvovaginal candidiasis treatment.

Vulvovaginal candidiasis (VVC) is characterized by inflammatory changes in the vaginal mucosa caused by abnormal colonization of Candida species. Traditional topical therapies using reference antifungal drugs usually present several issues and limitations for VVC treatment. Thus, the interest in new vaginal formulations, mainly those based on compounds from natural origin, has been growing over the last years. Methanolic extract from the plant species Mitracarpus frigidus (Willd. Ex Reem Schult.) K. Schum (MFM) has presented potential antifungal activity against C. albicans vaginal infection. Here, we aimed to develop and characterize a gynecological gel formulation based on chitosan containing MFM and to evaluate its anti-C. albicans effectiveness in the treatment of VVC. First, MFM was incorporated into a gel formulation based on chitosan in three final concentrations: 2.5 %, 5.0 %, and 10.0 %. Next, these gel formulations were subjected to stationary and oscillatory rheological tests. Finally, the gel was tested in an experimental VVC model. The rheological tests indicated pseudoplastic fluids, becoming more viscous and elastic with the increase of the extract concentration, indicating intermolecular interactions. Our in vivo analyses demonstrated a great reduction of vulvovaginal fungal burden and infection accompanied with the reduction of mucosal inflammation after MFM chitosan-gel treatment. The present findings open perspectives for the further use of the MFM-chitosan-gel formulation as a therapeutic alternative for VVC treatment.