1,720,973 research outputs found
Profilo molecolare e genetico negli adenocarcinomi nasosinusali di tipo intestinale (ITAC)
INTRODUZIONE. Il valore dei parametri istopatologici convenzionali nel predire la prognosi è dibattuto per quanto riguarda gli adenocarcinomi nasali di tipo intestinale (ITAC), richiedendo la scoperta di nuovi fattori prognostici. Il lavoro ha studiato il valore prognostico delle caratteristiche del microambiente tumorale (TME) e il panorama genetico in questo istotipo tumorale.
METODI. È stata effettuata un’analisi retrospettiva di 178 pazienti affetti da ITAC trattati presso l’Università dell’Insubria di Varese, tra il 2002 e il 2020. Le densità di linfociti intraepiteliali (EIL) e intratumorali (TIL) CD3+, CD4+, CD8+, l'espressione di MHC di classe I e II e gli score di espressione di PD-L1 sono stati valutati e correlati con la prognosi. Lo studio genetico ha incluso l'analisi NGS in 21 casi e l'analisi SALSA MLPA per delezioni/duplicazioni in 19 casi.
RISULTATI. L'analisi del TME è stata eseguita in 42 su 178 pazienti totali. PD-L1 è risultato espresso principalmente dalle cellule infiammatorie, con PD-L1 TPS>0 nel 2,4% e PD-L1 CPS>1 nel 31% degli ITAC. Gli ITAC mucinosi hanno mostrato valori di PD-L1 CPS e infiltrati intratumorali CD4+ inferiori rispetto agli altri sottotipi. Una relazione non lineare è emersa per TIL CD4+ e CD3+ nei confronti di OS e DFS, rispettivamente. Associazioni significative con OS e DFS sono state osservate per TIL CD3+, CD4+, CD8+ e PD-L1 CPS nell'analisi univariata. Tutti gli infiltrati intratumorali e l’espressione di MHC-I sulle cellule tumorali sono risultati associati ad OS in modelli multivariati. I TIL CD4+ e l'infiltrazione dei margini sono risultati associati a peggiore OS nell'analisi multivariata. I geni frequentemente mutati nella serie sono risultati essere ERBB2, KRAS, PIK3CA, HRAS e NRAS. La duplicazione/amplificazione di EGFR è stata osservata nel 73,7% dei casi.
CONCLUSIONE. La densità dei TIL, soprattutto considerando i TIL CD4+, sembra essere un fattore prognostico indipendente in questo istotipo tumorale. Il panorama genetico degli ITAC si dimostra essere eterogeneo, con l'amplificazione dell'EGFR come alterazione di più frequente riscontro. Per convalidare i risultati di questa analisi preliminare saranno necessari studi multicentrici su casistiche più ampie.INTRODUCTION. The prognostic value of conventional histopathological parameters in sinonasal Intestinal Type Adenocarcinoma (ITAC) is debated, demanding for exploration of new factors. This study assessed Tumor Microenvironment (TME) features and their prognostic impact in ITAC, along with a description of the genetic landscape.
METHODS. A retrospective analysis of 178 ITAC patients treated at the University of Insubria, Varese, between 2002 and 2020 was performed. CD3+, CD4+, CD8+ EILs/TILs densities, MHC-I, MHC-II, and PD-L1 expression were evaluated and correlated with prognosis. The genetic study included NGS analysis in 21 ITACs and SALSA MLPA analysis for deletions/duplications in 19 ITACs.
RESULTS. TME analysis was performed in 42 of the 178 patients. PD-L1 was mainly expressed by inflammatory cells, with PD-L1 TPS>0 in 2.4% and PD-L1 CPS1 in 31% of ITACs. Mucinous ITACs showed lower PD-L1 CPS and CD4+ TILs. Non-linear associations were observed between CD4+ and CD3+ TILs with OS and DFS, respectively. Significant associations with OS and DFS were noted for CD3+, CD4+, CD8+ TILs, and PD-L1 CPS in univariate analysis. All TILs and MHC-I tumor expression were associated with OS in multivariate models. CD4+ TILs and positive margins were associated with worse OS in a comprehensive multivariate model. Frequently mutated genes included ERBB2, KRAS, PIK3CA, HRAS, and NRAS. EGFR duplication/amplification occurred in 73.7% of cases.
CONCLUSION. TIL density, especially considering CD4+ TILs, appears to be an independent prognostic factor for ITACs. The genetic landscape of ITACs was heterogeneous, with EGFR amplification being the most common alteration. Larger multicentric studies are needed to validate these findings
Skull base osteoradionecrosis: from pathogenesis to treatment
Purpose of review This review aims to provide a comprehensive analysis of skull base osteoradionecrosis (ORN), a severe and rare complication of radiotherapy for head and neck malignancies. It explores pathogenesis, clinical presentation, diagnostic strategies, and management approaches, emphasizing the importance of multidisciplinary care in addressing this challenging condition. Recent findings Skull base ORN results from radiotherapy-induced tissue damage, characterized by hypovascularity, hypoxia, and necrosis, often compounded by secondary infections. Advances in radiotherapy techniques, such as intensity-modulated radiotherapy and heavy particles, have reduced ORN incidence, though cases persist, particularly in high-dose radiotherapy fields. Emerging treatments, including hyperbaric oxygen therapy and the pentoxifylline-tocopherol protocol, show promise but lack robust evidence for standardized use. Surgical interventions, especially those incorporating vascularized tissue reconstruction, have demonstrated favorable outcomes in refractory cases. Recent studies underscore the utility of multimodal imaging techniques, including MRI and PET/CT, for distinguishing ORN from tumor recurrence. Summary Skull base ORN represents a complex and potentially life-threatening condition requiring tailored, multidisciplinary management. Although advancements in diagnostics and therapeutics have improved outcomes, significant challenges remain, particularly in developing standardized protocols. Further research is needed to refine treatment strategies and improve evidence-based practices for this entity
A Surgical Variant of the Pre-Lacrimal Approach to the Maxillary Sinus
When dealing with maxillary sinus pathology, some areas of the sinus remain difficult to examine. In this regard, the pre-lacrimal approach is a minimally invasive technique to reach anterolateral areas of the maxillary sinus while preserving the physiological nasal function
Symptomatic ecchordosis physaliphora of the upper clivus: an exceedingly rare entity
Objective This paper highlights the management of 5 patients affected by symptomatic ecchordosis physaliphora (EP), treated via endoscopic endonasal transsphenoidal-transclival approach and contextual multilayer skull base reconstruction. A detailed analysis of each case is provided, along with the review of the current body of literature. Methods A retrospective review of patients treated by means of endoscopic endonasal approach for EP from 2010 to 2020 in the Otolaryngology and Neurosurgery Departments of a tertiary-care referral center for endoscopic skull base surgery was analyzed. Only adult patients with a definitive histopathological and immunohistochemical diagnosis of EP were included in the study. A systematic literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed for EP. Results Five cases of EP were retrieved and included in the study. Four patients presented with CSF leakage: in two cases after minor head trauma, in one case with associated bacterial meningitis, and in one case as only referred symptom. One patient complained diplopia due to VI cranial nerve palsy. No complications or recurrences of the disease were observed after a median follow-up of 37.2 months (range, 18-72 months). A total of 27 studies were identified with the systematic literature review, encompassing 30 patients affected by symptomatic EP who were addressed to surgical treatment. Twenty-five patients underwent complete surgical removal of the EP, while in 5 cases, only subtotal resection was performed. Conclusions EP might result in a "locus minoris resistentiae" of the skull base, predisposing, in rare cases, to CSF leakage and meningitis, spontaneously or after minor trauma. In cases of symptomatic EP, endoscopic endonasal transsphenoidal-transclival approach represents a safe and effective technique for both EP resection and contextual skull base reconstruction
Transoral robotic surgery in the management of a tongue base schwannoma
Schwannomas are the most common benign tumors arising from the peripheral nerve sheath, and the intraoral location is very atypical, representing less than 1% of all cases. Surgical excision is the treatment of choice, and a variety of surgical approaches have been described. The authors report the first described case of tongue base schwannoma treated with transoral robotic surgery (TORS). A 47-years-old female patient complaining mild dysphagia and snoring, presented a submucosal swelling at the right side of the tongue base. MRI showed a large well-circumscribed solid mass, homogeneously isointense in T1WI and hyperintense on T2WI, with no lymph node metastasis. According to size, location and radiological characteristic of the mass a TORS approach was chosen. An extracapsular dissection was performed, and the lesion was completely removed with no intraoperative complications. The final diagnosis based on histopathological examination and IHC analysis (S-100 positive) was a schwannoma of the tongue base. The post-operative course was uneventful, and no recurrence was observed after 6 months of follow-up. This study demonstrates the feasibility of TORS in the treatment of a tongue base schwannoma. This is a valid alternative to the common transoral approach in order to avoid more invasive external approaches, and further studies are recommended in order to clarify if this approach could be proposed as the first line treatment in selected cases
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Surgical margin assessment and prognostic impact in sinonasal cancers: a systematic review and meta-analysis
Objective. Surgery remains a cornerstone in treatment of sinonasal malignancies, but the prognostic role of margin status is controversial. This systematic review and meta-analysis evaluated the prognostic significance of surgical margins in sinonasal cancer and their impact on survival, alongside key challenges in its evaluation. Methods. A systematic search in PubMed, Scopus, and Web of Science identified 64 studies (34,120 patients). Results. The overall margin infiltration rate was 33.2%, varying widely across studies (4.5-88.2%) and histotypes, and was the highest in adenoid cystic carcinoma (ACC, 61.5%). Meta-analysis of 31 studies showed positive margins were associated with worse survival (overall survival, odds ratio [OR] 2.61; disease-specific survival, OR 5.89; disease-free survival, OR 4.40). Squamous cell carcinoma, olfactory neuroblastoma, and mucosal melanoma had the strongest correlation with margin status, while for ACC and adenocarcinomas statistical significance was not reached. High heterogeneity was noted across studies, alongside inconsistent margin classification, distance thresholds, and use of frozen sections, limiting cross-study comparability. Conclusions. This study confirms the prognostic value of surgical margins, but underscores the urgent need for standardised definitions to improve prediction of oncologic outcomes and clinical decision-making
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