Innovative Use of an Injectable, Self-Healing Drug-Loaded Pectin-Based Hydrogel for Micro- and Supermicro-Vascular Anastomoses.

Microvascular surgery plays a crucial role in reconnecting micrometer-scale vessel ends. Suturing remains the gold standard technique for small vessels; however, suturing the collapsed lumen of microvessels is challenging and time-consuming, with the risk of misplaced sutures leading to failure. Although multiple solutions have been reported, the emphasis has predominantly been on resolving challenges related to arteries rather than veins, and none has proven superior. In this study, we introduce an innovative solution to address these challenges through the development of an injectable lidocaine-loaded pectin hydrogel by using computational and experimental methods. To understand the extent of interactions between the drug and the pectin chain, molecular dynamics (MD) simulations and quantum mechanics (QM) calculations were conducted in the first step of the research. Then, a series of experimental studies were designed to prepare lidocaine-loaded injectable pectin-based hydrogels, and their characterization was performed by using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and rheological analysis. After all the results were evaluated, the drug-loaded pectin-based hydrogel exhibiting self-healing properties was selected as a potential candidate for in vivo studies to determine its performance during operation. In this context, the hydrogel was injected into the divided vessel ends and perivascular area, allowing for direct suturing through the gel matrix. While our hydrogel effectively prevented vasospasm and facilitated micro- and supermicro-vascular anastomoses, it was noted that it did not cause significant changes in late-stage imaging and histopathological analysis up to 6 months. We strongly believe that pectin-based hydrogel potentially enhanced microlevel arterial, lymphatic, and particularly venous anastomoses.

Relationship between PD-L1 expression and prognostic factors in high-risk cutaneous squamous and basal cell carcinoma.

This study aimed to investigate the programmed cell death-ligand 1 (PD-L1) expression in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) and its relationship with prognostic factors in tumors that are not in the head and neck region and are therefore relatively less exposed to the sun. This retrospective cross-sectional study included 25 invasive cSCC and 42 BCC cases with a diameter ≥ 2 cm located outside the head and neck region from 2010 to 2018. The biopsy samples were examined based on the membranous PD-L1 (22C3 clone) staining. Staining results were scored as follows: 0, no staining (negative); 1, < 10% PD-L1 positivity of tumor cells; and 2, ≥ 10% PD-L1 positivity of tumor cells. PD-L1 positivity was not seen in any BCC cases, whereas 11 (44%) of cSCC cases were PD-L1 positive. No significant relationship was observed between PD-L1 expression and prognostic parameters, including tumor diameter, tumor depth, and lymphovascular or perineural invasion in the cSCC group. PD-L1 expression was not associated with prognostic factors in the early stages of BCC and SCC located outside the head and neck region. Therefore, investigating the PD-L1 expression seems to be more relevant in patients with advanced-stage disease.

Analysis of interobserver reproducibility in grading dysplastic nevi: Results of the application of the 2018 World Health Organization grading criteria.

BACKGROUND: We aimed to determine whether the histopathological grading of dysplastic nevi is an objective endeavor, considering interobserver variability, according to 2018 World Health Organization (WHO) criteria. METHODS: In total, 179 cases of dysplastic nevi, with high and moderate degree of atypia, diagnosed and graded according to the previous criteria were reviewed by three pathologists. Then, the observers graded the dysplastic nevi as low or high according to 2018 WHO criteria. RESULTS: Grading of dysplastic nevi was in complete agreement in 99 out of 179 cases across three observers with a fair level of overall interobserver agreement (multirater κfree : 0.40). The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. CONCLUSIONS: The 2018 WHO criteria for dysplastic nevus will ensure a common approach to the diagnosis and grading of dysplastic nevi. However, histopathological criteria, such as cytological features and focal continuous basal proliferation of melanocytes, should be improved so as to ensure a more accurate surgical approach and risk assessment.

Proliferating Pilar Tumors: Can Immunohistochemistry Differentiate Benign and Malignant Forms?

BACKGROUND: Proliferating pilar tumor (PPT) is an adnexal tumor of purported differentiation toward the follicular outer root sheath. Immunohistochemistry has been suggested to differentiate between benign and malignant forms. METHODS: Eleven benign (PPT) and 9 malignant PPT lesions were reviewed; Ki67, p27, and p53 were applied. The staining intensity (strong, moderate, weak, and negative), positive cell numbers, and marker indexes (%) were scored using image-analysis software (ViraSoft). RESULTS: Overall, there was no significant correlation between Ki67 and p53 and histopathological features. However, malignant PPTs had significantly lower numbers of p27-positive cells (P = 0.030). CONCLUSIONS: Our study includes the largest group of patients in whom image analysis of p53, Ki67, and p27 has been used to try to separate benign from malignant lesions. Although there were no significant differences regarding Ki67 and p53, malignant lesions have a statistically lower expression of p27. Further studies may be needed to determine the clinical usefulness of image analysis in this differential diagnosis.