1,721,092 research outputs found
Caratterizzazione dei melanomi mucosi: studio del microambiente immunologico e del profilo molecolare per sviluppare terapie mirate
Full text linkI melanomi mucosi (MM) sono neoplasie rare che originano dai melanociti delle mucose con una patogenesi non correlata alla fotoesposizione solare. Il distretto testa-collo, in particolare il cavo orale e il tratto sinonasale, rappresentano la sede più comune di insorgenza. La prognosi di questa neoplasia è infausta ed i motivi che possano spiegare questa aggressività sono ancora sconosciuti e richiedono studi di biologia molecolare specifici. È stata condotta un’analisi retrospettiva su 48 pazienti affetti da MM sinonasale, trattati in due centri italiani di riferimento dal 2000 al 2017. I dati clinici e i fattori prognostici sono stati analizzati. Materiale tissutale adeguato per ogni singolo caso è stato selezionato negli archivi. È stata condotta un’analisi immunoistochimica per analizzare il microambiente immunologico dei casi tumorali, utilizzando anticorpi specifici (CD45, CD8, CD3, CD163, CD20, CD66b, BDCA2, CD56, CD274/PD-L1, HLA-DP, DQ, DR. The PD-L1, β-catenin, e PTEN). Sono state generate delle linee di coltura cellulare e sono state identificate cellule staminali tumorali specifiche. L’analisi mutazionale genetica è stata condotta utilizzando il sistema Sequenom MassArray ed il sistema il targeted next generation sequencing (NGS). Delezioni/duplicazioni delle regioni cromosomiche 1p, 3, 6 e 8 sono state ricercate utilizzando le sonde SALSA MLPA (Multiplex Ligation-dependent Probe Amplification) P027 Uveal Melanoma. I risultati del presente studio hanno dimostrato che questa neoplasia può essere considerata come un “noninflammed tumor” con un microambiente immunologico caratterizzato da scarso infiltrato di cellule CD45, CD8 e CD3. Inoltre, l’espressione di PDL-1 è risultata sempre assente. Questo ambiente immunologico “freddo” potrebbe spiegare l’efficacia limitata dei protocolli immunoterapici con doppio inibitore di checkpoint immunitario (anti-PD-1/e anti-CTLA4) che sono stati impiegati negli ultimi anni. L’analisi mutazionale ha evidenziato la presenza di mutazioni somatiche nei geni NRAS, KRAS e KIT solo in 14/31 casi. In particolare, non sono state osservate mutazioni di BRAF in nessuno dei casi analizzati, cosa che è completamente in contrasto con il profilo genetico che classicamente caratterizza i melanomi cutanei. Dal punto di vista genomico, è stato possibile descrivere un profilo muticromosomico specifico di alterazioni nel numero di copie, caratterizzato da “loss” del cromosoma 3p-q, 1p e 8p. Questo profilo, quando presente, è in grado di identificare un sottogruppo di pazienti caratterizzato da prognosi infausta ed elevato rischio di metastatizzazione precoce. Sebbene questo profilo di alterazioni genomiche non abbia una ricaduta terapeutica specifica al momento attuale, questo risultato potrebbe essere molto utile per aiutare nell’identificazione dei pazienti a prognosi peggiore ed elevato rischio di metastasi che potrebbero essere candidati a forme di trattamento neoadiuvante e/o adiuvante più intensificate. In conclusione, questo studio dimostra come il MM rappresenti un’entità tumorale completamente diversa dal melanoma cutaneo dal punto di vista della patogenesi, dell’epidemiologia, del decorso clinico e del profilo genetico-molecolare. Per questo motivo è importante inquadrare questi pazienti in modo specifico per proporre loro forme di trattamento mirato. A questo proposito, terapie target molecolare con MEK-inhibitors, PI3K-AKT-mTOR inhibitors, CDK4/6 inhibitors, KRASG12C inhibitors, tyrosine kinase inhibitors (Imatinib, Nilotinib, Avapritinib), e multikinase inhibitors (Regorafenib) potrebbero essere proposte per questi pazienti, in base al loro stato mutazionale. Inoltre, trattamenti immunoterapici combinati con inibitori di doppio check point immunitario (anti-CTLA-4 e anti-PD-1) potrebbero essere usati per questi pazienti sia nel setting neoadiuvante che come forma di trattamento adiuvante.Mucosal melanoma (MM) is a highly aggressive and rare form of melanoma arising from mucosal melanocytes with a pathogenesis unrelated to sun exposure. Head and neck, in particular the oral cavity and the sinonasal tract (SN), represent the most common MM sites. MM outcome is very poor and the reasons behind this aggressive clinical behavior are only partially understood.
A retrospective review of 48 patients treated for sinonasal tract mucosal melanoma in two Italian tertiary care referral centres (University of Insubria, Varese, and University of Brescia) from 2000 to 2017 was performed. Clinical data, survival outcomes and prognostic factors have been fully analyzed. Tissue blocks were retrieved from Institutional archives.
Immunohistochemical evaluation of the immunological tumor microenvironment was performed by testing different antibodies, such as CD45, CD8, CD3, CD163, CD20, CD66b, BDCA2, CD56, CD274/PD-L1, HLA-DP, DQ, DR. The PD-L1, β-catenin, and PTEN immunostaining were also performed. Cell lines were generated and cancer stem cells were identified. Gene mutation analysis was performed both using Sequenom MassArray system and targeted next generation sequencing (NGS) analysis. Deletions/duplications analysis of regions in chromosomes 1p, 3, 6 and 8 was performed using SALSA MLPA (Multiplex Ligation-dependent Probe Amplification) probemix P027 Uveal Melanoma.
We found that MM is a noninflammed tumor with an immune contexture poor of CD45, CD8 and CD3 positive cells. In addition to the scarce immune infiltration, PDL-1 expression is almost absent in MM. This “cold” immune contexture may explain the limited efficacy of immunotherapy, even in the form of double immune checkpoint inhibitor anti-PD-1/anti-CTLA4, which has been observed in MM patients.
When considering the molecular landscape of MM, we found somatic mutations only in 14/31 cases, mainly involving NRAS, KRAS and KIT. No BRAF mutations were found, in contrast with the genetic fingerprint of cutaneous melanoma.
From genomic viewpoint, we described a multichromosome copy number aberration signature characterized by chromosome 3p-q losses together with 1p loss and 8p loss, which is associated with poor prognosis and early systemic metastasization risk. Although this genomic signature at present does not have a direct therapeutic implication, it may be useful in identifying patients at high risk for early dissemination of disease and poor prognosis, who might benefit from intensification of systemic treatments in neoadjuvant or adjuvant setting.
In conclusion, we found that MM should be considered as clinical entity significantly different from cutaneous melanoma with regard to its pathogenesis, epidemiology, clinical characteristics and genetic-molecular fingerprint. As such, it is important to evaluate these patients as a separate subset in order to give patients realistic expectations for their disease course and to propose them specific forms of treatment. In this regards, in well selected cases, target-therapies with MEK-inhibitors, PI3K-AKT-mTOR inhibitors, CDK4/6 inhibitors, KRASG12C inhibitors, tyrosine kinase inhibitors (Imatinib, Nilotinib, Avapritinib), and multikinase inhibitors (Regorafenib) should be considered, based on the molecular profile. In addition, immunotherapy with double immune check points inhibitors (anti-CTLA-4 and anti-PD-1) might be used in selected cases both in neoadjuvant and adjuvant setting
Endoscopic endonasal approaches for treatment of craniovertebral junction tumours
No full textTumours involving the craniovertebral junction (CVJ) are challenging because of their local invasiveness and high recurrence rates, as well as their proximity to critical neurovascular structures and the difficulty of reconstructing the resulting skull base defect at this site. Several surgical techniques are currently available to access these lesions, including the far lateral, extreme lateral, direct lateral, transcervical, transoral and transnasal approaches. In this paper, application of the endoscopic endonasal approach (EEA) in the treatment of CVJ tumours is analysed. The indications, contraindications, preoperative workup, step-by-step surgical technique, skull base reconstruction options and postoperative management are described. The advantages and limitations of the EEA are also discussed. Finally, a systematic review of the literature is provided to elucidate the levels of evidence supporting the use of the EEA in this field. Employment of this approach to the CVJ has contributed to high success rates in achieving gross total resection of tumours and improvement in neurological symptoms. Intraoperative and postoperative complication rates are acceptable, with cerebrospinal fluid leakage being the major concern (with a 17–25% incidence). Moreover, in comparison with traditional approaches to the CVJ, the EEA provides lower rates of postoperative dysphagia and respiratory complications. Use of the EEA for treatment of CVJ tumours appears to be a rational alternative to the conventional transoral, transcranial and transcervical approaches in selected cases. Multidisciplinary teamwork including different specialists—such as medical and radiation oncologists, radiologists, otorhinolaryngologists and neurosurgeons—is strongly recommended for the purpose of offering the best treatment strategy for the patient
Ultrasonic Scalpel-Assisted Endoscopic Endonasal Surgery of Infratemporal Fossa: Our First Impressions
No full textBACKGROUND: The endoscopic endonasal transpterygoid approach is emerging as a valid option for treating selected tumors in the infratemporal fossa. Compared with traditional open approaches, the endoscopic endonasal approach presents more difficulty in controlling bleeding and less choice in surgical instruments for endoscopic tumor dissection, which is often performed with bipolar forceps or steel dissectors.CASE DESCRIPTION: We describe the use of an ultrasonic scalpel device for performing endoscopic endonasal resection of 2 rare infratemporal fossa tumors (mature teratoma and hemangiopericytoma), which has not been reported in the literature so far. We also review the literature on endoscopic ultrasonic scalpel use.CONCLUSIONS: The ultrasonically activated scalpel is a safe, effective and simple to use device, which achieved excellent hemostasis and did not damage adjacent neurovascular structures
Prognostic value of pretreatment peripheral blood markers in paranasal sinus cancer: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio
No full textBackground: Pretreatment hematological markers have emerged as prognostic factors for several cancers. The purpose of this study was to present our investigation of the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting recurrence and mortality for patients with primary sinonasal cancers (SNCs). Methods: We carried out a retrospective review of patients with SNC who had been treated using endoscopic approaches from 2002 to 2014 at a single institute. The endpoints analyzed were overall survival (OS) and disease-free survival (DFS). Results: Of 365 patients treated, 215 fulfilled the inclusion criteria. Analysis of epithelial tumors (adenocarcinoma and carcinoma) and advanced-stage cancers (pT3–T4) showed shorter OS and DFS in those patients with higher NLR and PLR. Furthermore, the NLR and PLR were revealed as independent prognostic factors for DFS, with a reduced risk of recurrence in patients with NLR <2.6 (hazard ratio [HR], 0.39; p =.02) and PLR <156.9 (HR, 0.34; p =.001). Conclusion: High pretreatment NLR and PLR are associated with poor prognosis in patients affected by epithelial advanced-stage SNC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 730–736, 2017
Thyroglossal Duct Cyst at the Base of Tongue: The Emerging Role of Transoral Endoscopic-Assisted Surgery
No full textCystic lesions involving the tongue base are rare, generally presenting in pediatric patients, and they may encompass different pathologies such as ranula, lingual ectopic thyroid, thyroglossal duct cyst (TDC), dysontogenetic cysts, benign, and malignant tumors.This paper describes the case of a 19-year-old girl with phonation impairment and mild dysphagia due to limited tongue protrusion and movements. Radiologic examinations revealed a bulky cystic lesion at the base of tongue with displacement of extrinsic lingual muscles. A minimally invasive transoral removal of the mass was performed under the assistance of the endoscopic system. The histopathologic analysis confirmed the diagnosis of intralingual TDC. After 2 years of clinical and radiologic follow-up, no recurrence of disease was observed and the patient is completely asymptomatic.The present experience suggests that the endoscopic-assisted transoral removal of intralingual TDC can be proposed as a safe and effective procedure, alternative to traditional transcervical surgery as well as to transoral robotic surgery, leading to very appealing cosmetic results and encouraging functional outcomes in terms of phonation and swallowing. Preoperative radiologic examinations should be performed for an accurate diagnosis and appropriate selection of patients
Transnasal endoscopic partial maxillectomy: Operative nuances and proposal for a comprehensive classification system based on 1378 cases
No full textBackground: Despite the development of functional endoscopic endonasal surgery, there are still areas of the maxillary sinus that remain technically difficult to access using a standard middle meatal antrostomy as well as deep-seated skull base lesions requiring expanded transmaxillary approaches. Methods: All patients who underwent transnasal endoscopic partial maxillectomy (TEPM) in a single institution from 2000 to 2014 were retrospectively reviewed. The TEPM was classified into 5 types according to the anatomic structures progressively removed and to the access provided. Results: The TEPM was performed in 1378 patients for the management of: inflammatory diseases in 513 cases (37%), benign sinonasal tumors in 425 cases (31%), skull base malignancies in 285 cases (21%), and as a corridor to address deep-seated skull base lesions in 155 cases (11%). Conclusion: The TEPM is a stepwise approach offering increasing access that can be tailored to different maxillary, sinonasal, and skull base pathologies with minimal morbidity for patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 754–766, 2017
Palatovaginal (pharyngeal) artery: clinical implication and surgical experience
No full textThe palatovaginal or pharyngeal artery is a small branch of the internal maxillary artery supplying the nasopharynx. Bleeding from this artery is exceptional and only one case of traumatic epistaxis from this artery has been reported previously. We report a case of a 66-year-old male presenting with right recurrent posterior epistaxis. Endoscopic dissection of the pterygopalatine fossa and direct visualization of the palatosphenoidal canal permitted to identify the origin of bleeding, and coagulation of the pharyngeal artery solved the epistaxis. Although rare, intractable posterior epistaxis may arise from the pharyngeal artery. The anatomical knowledge of this artery and of the palatosphenoidal canal is of outmost importance in endoscopic transpterygoid and nasopharyngeal procedures, to identify the vidian canal, evaluate nasopharyngeal cancer spread in the pterygopalatine fossa, reduce bleeding during surgery of the nasopharynx, and harvest adequately the pedicle of the nasoseptal flap
Endoscopic Endonasal Management of Orbital Pathologies
No full textBased on the anatomic relationship between sinonasal complex and orbit, endoscopic transnasal procedures could be a smart solution for approaching the medial orbital region. These techniques should be considered a valid option for optic nerve or orbital wall decompression in cases of Graves ophthalmopathy and post-traumatic optic neuropathy as well as for addressing extraconal or intraconal lesions placed medially to the optic nerve course. This article describes the anatomic principles, indications, technical nuances, and limitations of the endoscopic endonasal approaches for the management of selected orbital pathologic abnormalities
Comprehensive access strategies to the frontal sinus
No full textPurpose of review: Despite the impressive evolutions in endoscopic endonasal approaches and instrumentations, the frontal sinus remains a challenging area. Different surgical options have been described over the years, but the main criticism lies in choosing the most suitable approach for a given case, based on the anatomy of each patient and the disease to treat. The purpose of this study is to provide a comprehensive review of surgical access strategies currently available to address the frontal sinus, including both endonasal and traditional external procedures, analysing indications, contraindications, complications and outcomes. Recent findings: Frontal sinus surgery includes minimally invasive endonasal approaches (balloon dilatation, Draf type I); extended endonasal approaches (Draf type IIA-IIB-IIC, Draf type III and their modifications via orbital transposition and contralateral pyriform aperture resection); external procedures (superior eyelid incision, frontal osteoplastic flap, Riedel procedure, Riedel-Mosher operation); and combined approaches. Summary: Recent advances in endoscopic endonasal techniques have deeply reshaped the surgical options to manage frontal sinus diseases, in an attempt to minimize the invasiveness of the procedures and maximize their outcomes. Traditional external procedures should be used in selected cases nonamenable for endonasal surgery. The appropriate selection of cases appears to be of paramount importance to obtain successful outcomes
- …
