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BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

The enzyme topoisomerase II alpha (TOP2A) plays a critical role in DNA replication and cell proliferation, making it a promising target for cancer therapy. In epithelial ovarian cancer (EOC), TOP2A overexpression is associated with poor prognosis and resistance to conventional treatments. This review explores the biological functions of TOP2A in EOC and discusses its potential as a therapeutic target. We highlight studies on the mechanisms through which TOP2A contributes to tumor progression and recurrence. Additionally, we evaluate the clinical implications of targeting TOP2A, including the use of TOP2A inhibitors and their combination with novel drugs. We provide a comprehensive overview of the current understanding and future directions for targeting TOP2A in the management of EOC. [ABSTRACT FROM AUTHOR]

Objectives: In pituitary adenomas, examinations of surgical specimens have shown that dural invasion occurs in 42–85% of cases. No studies about dura mater invasion have been conducted specifically in acromegaly patients. The aim of the present study was to evaluate the relationship between histologically dural invasion and the main features of GH-secreting adenomas. Methods: This retrospective study included all consecutive acromegaly patients who underwent neurosurgery at our university hospital between 2017 and 2020. The following data were collected: (1) clinical, biochemical and morphological data at diagnosis, at three months, one year after neurosurgery, and at last follow-up; (2) pathological features (dura mater invasion, immunohistochemical analyses, proliferation index Ki-67, p53, and granulation pattern); and (3) radiological features on magnetic resonance images. Results: Of 35 acromegaly patients, 11 had dural invasion (INV+ 31%) and 24 did not (INV− 69%). GH levels at diagnosis were greater in INV+ patients (p = 0.02), and a GH value > 27 ng/mL was able to distinguish INV+ patients (Sensitivity 80%, Specificity 73%, AUC 0.760, p = 0.006). Indeed, patients with GH > 27 ng/mL at diagnosis had a tenfold greater risk of dura mater invasion (OR 10.7; 95% CI 1.74–65.27, p = 0.005). No differences were found in the other clinical, biochemical, morphological, radiological and pathological features. Regarding remission likelihood, IGF-1 levels at diagnosis were lower in cured patients (p = 0.03). Conclusions: The GH level at diagnosis is the only parameter significantly associated with dura mater invasion. Lower IGF-1 levels at diagnosis are significantly associated with remission one year after surgery. [ABSTRACT FROM AUTHOR]

Introduction: Ewing Sarcoma (EWS) has been reported in seven children with Down syndrome (DS). To date, a detailed assessment of this solid tumour in DS patients is yet to be made. Methods: Here,we characterise a chemo-resistantmediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches. Results: The tumour showed a neuroectodermal development driven by the EWSR1-FLI1 fusion. The inherited myeloperoxidase deficiency of the patient caused failure of neutrophil-mediated cell death and promoted genomic instability. Discussion: In this context, the tumour underwent genome-wide near haploidisation resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered rapid evolution of this EWS. [ABSTRACT FROM AUTHOR]

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position. [ABSTRACT FROM AUTHOR]

Schwannoma is a slow-growing benign encapsulated tumor that arises from Schwann cells. Ancient schwannoma is a rare histologic variant characterized by degenerative changes, usually in the context of a schwannoma with long evolution. Intraoral ancient schwannoma is extremely rare. A review of the literature revealed only thirty previously reported cases. This article aims to present and discuss the first case of ancient schwannoma of the anterior mandibular vestibule and to review the relevant literature on intraoral ancient schwannoma. [ABSTRACT FROM AUTHOR]

Introduction: Differentiated vulvar intraepithelial neoplasia (dVIN) is a high‐risk preinvasive vulvar lesion and precursor of human papillomavirus‐independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN‐VSCC) at first diagnosis. Material and methods: A historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan–Meier method and log‐rank test were used to estimate cancer risk or recurrent cancer risk differences and uni‐ and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN‐VSCC. Results: Seventy‐six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN‐VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5–128.0 months). VSCC recurrence absolute risk in treated dVIN‐VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5–94.8 months). At uni‐ and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN‐VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN‐VSCC patients on both uni‐ and multivariate regression analyses. Conclusions: Patients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long‐term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended. [ABSTRACT FROM AUTHOR]

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients' and oncologists' need from a pathology report. [ABSTRACT FROM AUTHOR]

Background: Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate subtype (PPTIDs), remains challenging. Methods: A literature review was conducted, navigating through anatomo-pathological, radiotherapy, and neurosurgical dimensions, aiming for a holistic understanding of these tumors. Results: PPTIDs, occupying an intermediate spectrum of malignancy, reveal diverse histological patterns, mitotic activity, and distinct methylation profiles. Surgical treatment is the gold standard, but when limited to partial removal, radiotherapy becomes crucial. While surgical approaches are standardized, due to the low prevalence of the pathology and absence of randomized prospective studies, there are no shared guidelines about radiation treatment modalities. Conclusion: Surgical removal remains pivotal, demanding a personalized approach based on the tumor extension. This review underscores the considerable variability in treatment approaches and reported survival rates within the existing literature, emphasizing the need for ongoing research to better define optimal therapeutic strategies and prognostic factors for PPTIDs, aiming for further and more detailed stratification among them. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high‐grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin‐fixed paraffin‐embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine‐valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Objective: To determine the prognostic role of systemic inflammatory markers for Stage I epithelial ovarian cancer (EOC). Materials and Methods: We performed a retrospective, single‐center, observational study. We included patients with Stage I EOC cancer undergoing primary surgery between 1993 and 2016. Inflammatory markers were assessed by analyzing blood samples collected at initial diagnosis before EOC surgery. We evaluated these markers' association with disease‐free survival (DFS) and cancer‐specific survival (CSS). Results: We included 176 women in our study. The neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were related to both DFS and CSS in the univariate analysis. In the multivariate Cox analysis, adjuvant chemotherapy (hazard ratio [HR] 0.17, 95% confidence interval [CI] 0.04–0.71, P = 0.02) and SII ≥730 (HR 6.84, 95% CI 1.30–35.9, P = 0.023) were independent predictors of DFS, while FIGO Stage IB–IC (HR 7.91, 95% CI 1.04–59.8, P = 0.04), NLR ≥3 (HR 56.8, 95% CI 7.46–433, P < 0.001) and PLR ≥169 (HR 49.1 95% CI 11.1–217.8, P = 0.005) were independent predictors of CSS. Conclusions: Systemic inflammatory markers are easily obtainable from patients' routine blood analyses and may represent inexpensive and reproducible prognostic markers in early‐stage EOC. Synopsis: Systemic inflammatory markers are related to disease‐free survival and cancer‐specific survival for Stage I epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Over the past two years, the scientific community has witnessed an exponential growth in research focused on identifying prognostic biomarkers for melanoma, both in pre-clinical and clinical settings. This surge in studies reflects the need of developing effective prognostic indicators in the field of melanoma. The aim of this work is to review the scientific literature on the most recent findings on the development or validation of prognostic biomarkers in melanoma, in the attempt of providing both clinicians and researchers with an updated broad synopsis of prognostic biomarkers in cutaneous melanoma. While the field of prognostic biomarkers in melanoma appears promising, there are several complexities and limitations to address. The interdependence of clinical, histological, and molecular features requires accurate classification of different biomarker families. Correlation does not imply causation, and adjustments for confounding factors are often overlooked. In this scenario, large-scale studies based on high-quality clinical trial data can provide more reliable evidence. It is essential to avoid oversimplification by focusing on a single biomarker, as the interactions among multiple factors contribute to define the disease course and patient's outcome. Furthermore, implementing well-supported evidence in real-life settings can help advance prognostic biomarker research in melanoma. [ABSTRACT FROM AUTHOR]