Melanin-Based Nanoparticles for Lymph Node Tattooing: Experimental, Histopathological and Ultrastructural Study.

In breast cancer, Targeted Axillary Dissection (TAD) allows for the selective excision of the sentinel lymph node (SLN) during primary tumor surgery. TAD consists of the resection of labelled SLNs prior to neoadjuvant chemotherapy (NACT). Numerous clinical and preclinical studies have explored the use of carbon-based colloids for SLN tattooing prior to NACT. However, carbon vectors show varying degrees of inflammatory reactions and, in about one fifth of cases, carbon particles migrate via the lymphatic pathway to other nodes, causing the SLN to mismatch the tattooed node. To overcome these limitations, in this study, we explored the use of melanin as a staining endogenous pigment. We synthesized and characterized melanin-loaded polymeric nanoparticles (Mel-NPs) and used them to tattoo lymph nodes in pig animal models given the similarity in the size of the human and pig nodes. Mel-NPs tattooed lymph nodes showed high identification rates, reaching 83.3% positive identification 16 weeks after tattooing. We did not observe any reduction in the identification as time increased, implying that the colloid is stable in the lymph node tissue. In addition, we performed histological and ultrastructural studies to characterize the biological behavior of the tag. We observed foreign-body-like granulomatous inflammatory responses associated with Mel-NPs, characterized by the formation of multinucleated giant cells. In addition, electron microscopy studies showed that uptake is mainly performed by macrophages, and that macrophages undergo cellular damage associated with particle uptake.

Association between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis.

Inherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS.

Liver tissue remodeling following ablation with irreversible electroporation in a porcine model.

Irreversible electroporation (IRE) is a method of non-thermal focal tissue ablation characterized by irreversibly permeabilizing the cell membranes while preserving the extracellular matrix. This study aimed to investigate tissue remodeling after IRE in a porcine model, especially focusing on the extracellular matrix and hepatic stellate cells. IRE ablation was performed on 11 female pigs at 2,000 V/cm electric field strength using a versatile high-voltage generator and 3 cm diameter parallel-plate electrodes. The treated lobes were removed during surgery at 1, 3, 7, 14, and 21 days after IRE. Tissue remodeling and regeneration were assessed by histopathology and immunohistochemistry. Throughout the treated area, IRE led to extensive necrosis with intact collagenous structures evident until day 1. From then on, the necrosis progressively diminished while reparative tissue gradually increased. During this process, the reticulin framework and the septal fibrillar collagen remained in the necrotic foci until they were invaded by the reparative tissue. The reparative tissue was characterized by a massive proliferation of myofibroblast-like cells accompanied by a complete disorganization of the extracellular matrix with the disappearance of hepatic architecture. Hepatic stellate cell markers were associated with the proliferation of myofibroblast-like cells and the reorganization of the extracellular matrix. Between 2 and 3 weeks after IRE, the lobular architecture was almost completely regenerated. The events described in the present study show that IRE may be a valid model to study the mechanisms underlying liver regeneration after extensive acute injury.

Retroperitoneal mucinous cystadenoma.

INTRODUCTION: Retroperitoneal mucinous cystadenomas are rare tumors. Only 25 cases have been reported in the English literature until 2002. The histogenesis is unclear, diagnosis is never made preoperatively and surgery is the only treatment. CASE REPORT: We report an additional case.