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To retrospectively evaluate oncological outcomes in two groups of patients with pT4aN0 glottic SCC treated with total laryngectomy (TL) and neck dissection (ND) who underwent postoperative radiotherapy or exclusive clinical and radiological follow-up.It includes patients with pT4N0 glottic SCC who underwent TL and unilateral or bilateral ND with or without PORT. Divided in two comparison groups: the first group underwent adjuvant RT (TL-PORT); the second group referred to clinical and radiological follow-up (TL).PORT was associated with a better OS while no differences were found in terms of DSS. A better local control is achieved when PORT is administered while no differences in terms of regional and distant control rates were found. Bilateral ND positively impacts on the regional control while the PNI negatively impact the regional control.A tailored PORT protocol might be considered for pT4N0 glottic SCC treated with TL and ND, both considering the ND's extent and presence of PNI.

The adequacy of the surgical resection is the main controllable variable that is in the hands of the surgical team. There exists an unmet need to increase the rate of negative margins, particularly in cancers invading the craniofacial area. The study aimed 1) at developing a gross tumor model to be utilized for research, educational, and training purposes and 2) establishing the 3-dimensional relationship between the outer surface of the surgical specimen and tumor surface and test the effect of guiding ablations on cadavers with surgical navigation (SN).Seven cadaver heads were employed to create 24 craniofacial tumor models. Simulation of tumor resections was performed by 8 surgeons. Fourteen and 10 resections were performed with and without SN-guidance, respectively. Gross specimens underwent computed tomography and 3-dimensional analysis through dedicated software. Task load was assessed through a validated questionnaire. Tumor model reliability was studied based on visual analogue scale rate by surgeons and radiologists.SN reduced the rate of margin involvement, particularly by decreasing the percentage of the gross specimen outer surface involvement in areas uncovered by normal bony structures. The workload of SN-aided ablations was found to be medium-to-somewhat-high. Tumor model reliability was deemed satisfactory except for the extension to bony structures.A gross tumor model for head and neck cancers involving the craniofacial area was developed and resulted satisfactorily reliable from both a surgical and radiologic standpoint. SN reduced the rate of margin involvement, particularly by improving delineation of bone-uncovered areas.

Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosa of the oral cavity, pharynx, and larynx. The methylation levels of Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in ccfDNA are considered pan-cancer biomarkers and have shown prognostic value in preliminary reports in HNSCC. Liquid biopsy is a non-invasive procedure that collects tumor-derived molecules including circulating cell-free DNA (ccfDNA). Here, we developed a ddPCR-based assay to detect the DNA methylation levels of plasma circulating SEPT9 and SHOX2 in patients with HNSCC. We first set up the assay on commercial methylated and un-methylated DNA. Then, the dynamic changes of the methylation levels of SEPT9 and SHOX2 were quantified in 20 patients during the follow-up. The results highlighted: i) the capability of the ddPCR-based assay in detecting very low copies of methylated molecules; ii) the significant decrease in methylation levels of SEPT9 and SHOX2 in plasma of HNSCC patients at the first time points of follow-up respect to T0; iii) a different trend of longitudinally DNA methylation variations associable to the clinicopathological features of the patients. The absolute quantification of the methylation levels of SEPT9 and SHOX2 in HNSCC may be used for risk stratification and disease monitoring.

Background Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.Methods In this preclinical study, the performance of two bioengineered scaffolds, an hydrogel made of polyethylene glycol-chitosan (HyCh) and an hybrid core-shell combination of poly(L-lactic acid)/poly(\(\epsilon\)-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stem cells (hMSCs) (i.e. 1000, 2000, and 3000 cells/mm3), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.Results The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs (2000 and 3000 cells/mm3). The immunohistochemical profile showed significantly higher expression of both VEGF-A, in defects reconstructed with a PLA-PCL-HyCh, and osteopontin, in defects reconstructed with both scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.Conclusions Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes and molecular alterations, including TBXT duplication and SMARCB1 homozygous deletion. Partial or complete PTEN deficiency has also been observed. PTEN is a negative regulator of the Akt/mTOR pathway and hyperactivation of Akt/mTOR in cells lacking PTEN expression contributes to cell proliferation and invasiveness. This pathway is targeted by mTOR inhibitors and the availability of in vitro models of chordoma cells will aid in further investigating this issue. However, isolation and maintenance of chordoma cell lines are challenging and PTEN-deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human PTEN-deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including PTEN loss and expression of Brachyury and EMA. Moreover, we investigated the activation of the mTOR pathway and cell response to mTOR inhibitors. CH3 cells were sensitive to Rapamycin treatment suggesting that mTOR inhibitors may represent a valuable option for patients suffering from PTEN-deleted chordomas.

BACKGROUND AND PURPOSE: Prognosis in locally advanced head and neck cancer (HNC) is currently based on TNM staging system and tumor subsite. However, quantitative imaging features (i.e., radiomic features) from magnetic resonance imaging (MRI) may provide additional prognostic info. The aim of this work is to develop and validate an MRI-based prognostic radiomic signature for locally advanced HNC.MATERIALS AND METHODS: Radiomic features were extracted from T1- and T2-weighted MRI (T1w and T2w) using the segmentation of the primary tumor as mask. In total 1072 features (536 per image type) were extracted for each tumor. A retrospective multi-centric dataset (n = 285) was used for features selection and model training. The selected features were used to fit a Cox proportional hazard regression model for overall survival (OS) that outputs the radiomic signature. The signature was then validated on a prospective multi-centric dataset (n = 234). Prognostic performance for OS and disease-free survival (DFS) was evaluated using C-index. Additional prognostic value of the radiomic signature was explored.RESULTS: The radiomic signature had C-index = 0.64 for OS and C-index = 0.60 for DFS in the validation set. The addition of the radiomic signature to other clinical features (TNM staging and tumor subsite) increased prognostic ability for both OS (HPV- C-index 0.63 to 0.65; HPV+ C-index 0.75 to 0.80) and DFS (HPV- C-index 0.58 to 0.61; HPV+ C-index 0.64 to 0.65).CONCLUSION: An MRI-based prognostic radiomic signature was developed and prospectively validated. Such signature can successfully integrate clinical factors in both HPV+ and HPV- tumors.

Background Endoscopic transnasal transclival intradural surgery is limited by a high postoperative cerebrospinal fluid leak rate. The aim of this study was to investigate the role of three-dimensional printing to create a personalized, rigid scaffold for clival reconstruction. Methods Two different types of clivectomy were performed in 5 specimens with the aid of neuronavigation, and 11 clival reconstructions were simulated. They were repaired with polylactide, three-dimensional–printed scaffolds that were manually designed in a computer-aided environment based either on the real or on the predicted defect. Scaffolds were printed with a fused filament fabrication technique and different offsets. They were positioned and fixed either following the gasket seal technique or with screws. Postdissection radiological evaluation of scaffold position was performed in all cases. In 3 specimens, the cerebrospinal fluid leak pressure point was measured immediately after reconstruction. Results The production process took approximately 30 hours. The designed scaffolds were satisfactory when no offset was added. Wings were added during the design to allow for screw positioning, but broke in 30% of cases. Radiological assessment documented maximal accuracy of scaffold positioning when the scaffold was created on the real defect; accuracy was satisfactory when the predicted clivectomy was performed under neuronavigation guidance. The cerebrospinal fluid leak pressure point was significantly higher when the scaffold was fixed with screws compared with the gasket technique. Conclusions In this preclinical setting, additive manufacturing allows the creation of customized scaffolds that are effective in reconstructing even large and geometrically complex clival defects.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Background Nomograms applying the 8th edition of the TNM staging system aimed at predicting overall (OS), disease-specific (DSS), locoregional recurrence-free (LRRFS) and distant recurrence-free survivals (DRFS) for oral tongue squamous cell carcinoma (OTSCC) are still lacking. Methods A training cohort of 438 patients with OTSCC was retrospectively enrolled from a single institution. An external validation set of 287 patients was retrieved from two independent institutions. Results Internal validation of the multivariable models for OS, DSS, DRFS and LRRFS showed a good calibration and discrimination results with optimism-corrected c-indices of 0.74, 0.75, 0.77 and 0.70, respectively. The external validation confirmed the good performance of OS, DSS and DRFS models (c-index 0.73 and 0.77, and 0.73, respectively) and a fair performance of the LRRFS model (c-index 0.58). Conclusions The nomograms herein presented can be implemented as useful tools for prediction of OS, DSS, DRFS and LRRFS in OTSCC.

Objective: To date, no cases have been reported on the effects of COVID-19 in laryngectomees. Case Presentation: We herein presented two clinical cases of laryngectomized patients affected by COVID-19, detailing their clinical course and complications. Discussion: In our experience, permanent tracheostomy did not significantly affect the choice of treatment. However, dedicated devices and repeated tracheal toilettes may be needed to deal with oxygen-therapy-related tracheal crusting. Conclusion: In conclusion, laryngectomees should be considered a vulnerable population that may be at risk for worse outcomes of COVID-19 due to anatomical changes in their airways. The role of the ENT specialist is to guide airway management and inform the support-staff regarding specific needs of these patients.

Evidence on survival and major prognosticators after salvage surgery in recurrent sinonasal cancers (SNC) is limited.A retrospective, single-center study of recurrent SNC treated with salvage surgery between 1997 and 2019 was conducted. Univariate and multivariable analyses were performed to define a prognostic score for overall survival (OS).One hundred and eighteen patients were included. Recurrent SNC originated mostly in the naso-ethmoidal box (67.8%) and were mainly epithelial (76.2%), high-grade (49.2%), and locally advanced (rpT4, 60.1%) malignancies. Negative margins were achieved in 56.6% of cases. Two- and 5-year OS were 71.7% and 56%, respectively. The prognostic model included treatment modality for primary tumor, histology, rpT class, margin status, perineural invasion, and adjuvant radiotherapy and stratified patients into three prognostic groups (5-year OS: 84.4%, 44.9%, and 0%, respectively).Treatment of recurrent SNC can result in good long-term survival estimates with limited morbidity. Our score can provide excellent prognostic stratification.

Introduction: olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.Methods: we conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).Results: dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).Conclusions: this study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Oral tongue carcinomas represent more than half of the tumors arising in the oral cavity, a site with a high cancer specific mortality and impact on quality of life. Current guidelines are lacking for a standardized surgical approach of these tumors. The aim of this study is to compare two currently adopted surgical strategies, compartmental surgery (CTS) and wide local excision (WLE), with loco-regional control as the main oncological endpoint.An observational retrospective multicentric study was carried out enrolling a cohort of patients affected by oral tongue or floor of the mouth squamous cell carcinoma and surgically treated in 4 international tertiary referral centers. Survival analysis was performed by propensity-score matching approach and multivariable Cox regression analysis.A cohort of 933 patients was enrolled. CTS was applied in 113 patients (12.1%) and WLE in 820 (87.9%). Analyzing a propensity-score matched cohort (98 CTS vs. 172 WLE) and applying a survival multivariable modeling strategy on the whole cohort, both confirmed that CTS and WLE are comparable and oncologically safe. Parameters such as number of positive lymph nodes, depth of invasion, and lymphovascular invasion still represent the key prognosticators.The main goals for surgical resection of oral cancer remain its three-dimensional circumferential clearance with adequate margins and en-bloc removal of the tumor-lymph node tract, independently of the technique adopted (CTS or WLE). Further prospective studies including quality of life evaluation are needed to better understand if one of these approaches can provide superior functional outcomes.

© 2021 Wiley Periodicals LLC.Invasion of the internal carotid artery (ICA) has been historically considered a criterion of non-resectability of skull base cancer (SBC). Patients affected by SBC who underwent surgery including resection of ICA at two tertiary institutions were included. Demographics, oncologic, and surgical information, complications, and survival outcomes were retrospectively reviewed. Survival outcomes were calculated. Ten patients were included. Three surgical approaches (transnasal endoscopic, transorbital, and transpetrosal) were employed to resect the invaded/abutted tract(s) of the ICA. All patients underwent ICA temporary balloon occlusion test. In two patients, an extracranial-to-intracranial arterial bypass was harvested. Major neuromorbidity was observed in two patients. Perioperative mortality of the series was 10.0%. Mean overall survival was 27.2 months, with 2-year overall and progression-free survival rate of 88.9%. ICA resection is feasible as part of the ablation performed for very advanced SBCs. Survival outcomes are acceptable in adequately selected patients.

The clivus was defined as “no man’s land” in the early 1990s, but since then, multiple approaches have been described to access it. This study is aimed at quantitatively comparing endoscopic transnasal and microsurgical transcranial approaches to the clivus in a preclinical setting, using a recently developed research method. Multiple approaches were performed in 5 head and neck specimens that underwent high-resolution computed tomography (CT): endoscopic transnasal (transclival, with hypophysiopexy and with far-medial extension), microsurgical anterolateral (supraorbital, mini-pterional, pterional, pterional transzygomatic, fronto-temporal-orbito-zygomatic), lateral (subtemporal and subtemporal transzygomatic), and posterolateral (retrosigmoid, far-lateral, retrolabyrinthine, translabyrinthine, and transcochlear). An optic neuronavigation system and dedicated software were used to quantify the working volume of each approach and calculate the exposure of different clival regions. Mixed linear models with random intersections were used for statistical analyses. Endoscopic transnasal approaches showed higher working volume and larger exposure compared with microsurgical transcranial approaches. Increased exposure of the upper clivus was achieved by the transnasal endoscopic transclival approach with intradural hypophysiopexy. Anterolateral microsurgical transcranial approaches provided a direct route to the anterior surface of the posterior clinoid process. The transnasal endoscopic approach with far-medial extension ensured a statistically larger exposure of jugular tubercles as compared with other approaches. Presigmoid approaches provided a relatively limited exposure of the ipsilateral clivus, which increased in proportion to their invasiveness. This is the first anatomical study that quantitatively compares in a holistic way exposure and working volumes offered by the most used modern approaches to the clivus.

Adenoid cystic carcinoma (AdCC) is a rare disease, with indolent behavior and poor long-term survival. Many studies have evaluated the role of clinical and pathological factors at presentation on the risk of recurrence. In this study we investigated whether baseline demographic, clinical, and pathological characteristics at the time of primary curative treatment could influence the prognosis of patients once local and/or distant recurrence occurred.All patients affected by primary salivary gland AdCC and treated with curative surgery from January 1997 to June 2016 were reviewed, evaluating those who later developed loco-regional recurrence and/or distant metastasis. Time from the first relapse to death (recurrent/metastatic overall survival, RMOS) was considered the outcome of interest.Out of 87 surgically treated AdCC patients, 36 relapsing lesions were included. Median ages at first presentation and recurrence were 55 and 60-year-old, respectively; 58% were females. Median disease-free-interval (DFI) was 22.0 months. Five-year RMOS was 47%. At univariate analysis, age ≥ 60-year-old (HR:2.67, p = 0.030), primary tumor lympho-vascular invasion (LVI) (HR:5.38, p = 0.003), adjuvant radiotherapy (RT) in the primary setting (HR:0.37, p = 0.043), and DFI 30 months (HR:3.94, p = 0.008) significantly affected RMOS. Multivariable analysis confirmed the presence of LVI and shorter DFI as independent risk factors.Knowledge of baseline clinicopathological features is helpful in the prognostic stratification of patients with recurrent AdCC, with LVI as the most relevant baseline factor. Adjuvant RT demonstrated its protective role on survival even once recurrence occurred, further supporting its adoption in the primary setting.

Skull base and sinonasal tumors (SBSNTs) represent a considerable challenge for clinicians in view of their rarity, anatomical complexity of the site of origin, and great histological variety [...]

Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8+ T-cells. To this end, CD8+ T-cells counts were combined with well-established clinical variables and peripheral blood immune cell parameters. Through variable clustering, five metavariables (MV) were obtained and included descriptors of nodal (NODALMV) and primary tumor (TUMORMV) involvement, the frequency of myeloid (MYELOIDMV) or lymphoid (LYMPHOIDMV) peripheral blood immune cell populations, and the density of tumor-infiltrating CD8+ T-cells (TI-CD8MV). The clinical relevance of the MV was evaluated in the multivariable survival models. The NODALMV was significantly associated with all tested outcomes (p &lt, 0.001), the LYMPHOIDMV showed a significant association with the overall, disease-specific and distant recurrence-free survival (p &lt, 0.05) and the MYELOIDMV with the locoregional control only (p &lt, 0.001). Finally, TI-CD8MV was associated with distant recurrence-free survival (p = 0.029). Notably, the performance in terms of survival prediction of the combined effect of NODALMV and immune metavariables (LYMPHOIDMV, MYELOIDMV and TI-CD8MV) was superior to the TNM stage for most of the outcomes analyzed. These findings indicate that the analysis of the baseline host immune features are promising tools to complement clinical features, in stratifying the risk of recurrences.

Background Management of persistent juvenile angiofibroma (pJA) after transnasal endoscopic resection is controversial. To better understand its behavior, optimize treatment, and minimize morbidity, we report our experience in pJA focusing on follow-up strategies and disease progression. Methods A retrospective review of clinical records of all JA cases treated with endoscopic surgery at the Unit of Otorhinolaryngology of the University of Brescia between January 1994 and October 2015 was performed. Results Seventy-four cases were included. Mean follow-up was 113 months (6-266 months). Evolution of pJA was analyzed in 6 cases. Residual lesion size significantly decreased in 3 cases and 2 lesions did not show size variations; significant growth was detected in 1 case of intentional pJA, with diameter increasing by 2.2 mm/yr. Conclusions pJAs may have the tendency to regress spontaneously or remain stable. In selected cases, avoiding treatment of nongrowing pJA in critical areas is a prudent option.

Skull base cephaloceles (SBCs) are defined as herniation of intracranial content through the skull base and are classified based on composition, etiology, and topographic location. Anterior SBCs frequently protrude in the sinonasal cavity, and consequently are at potential risk of infection. Therefore, the current recommendation is to treat SBCs with the primary intent of preventing meningitis, and surgery represents the mainstay of treatment. Anterior SBCs may display a wide spectrum of severity and complexity, and in each case the risks and benefits of surgical approaches are to be carefully weighted based on thorough assessment of symptoms, age, general conditions, location and size of the lesion, as well as expertise of the surgeon. In the last 30 years, the evolution and diffusion of transnasal endoscopic surgery have substantially changed the surgical management of the majority of SBC. In the past, they were treated exclusively with open transcranial approaches that may be burdened by relevant morbidity and risk for severe complications. The transnasal endoscopic corridor now provides easy access to the lesion and different reconstructive strategies using endonasal pedicled flaps, without any external incision, cranioplasty or brain manipulation. However, there are still scenarios in which an exclusive transnasal endoscopic route is contraindicated. The aim of the present review was to provide an overview on the comprehensive management of anterior SBC, with a particular focus on lesions suitable for endoscopic surgery. Furthermore, special aspects of SBC management in children and adults will be highlighted.

Background We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. Methods Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan–Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. Results All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. Conclusions The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.

Objective Different surgical set-ups for endoscopic transsphenoidal surgery (ETS) have been described, but studies on their ergonomics are limited. The aim of this article is to describe present trends in the ergonomics of ETS. Design and Participants A 33-question, web-based survey was sent to North American Skull Base Society members in 2018 and 116 responded to it (16% of all members). Most respondents were from North America (76%), in academic practice (87%), and neurosurgeons (65%); they had more than 5 years of experience in ETS (73%), had received specific training (66%), and performed at least 5 procedures/mo (55%). Results Mean reported time for standard and complex procedures were 3.7 and 6.3 hours, respectively. The patient's body is usually positioned in a straight, supine position (84%); the head is in a neutral position (46%) or rotated to the side (38%). Most surgeons perform a binostril technique, work with a partner (95%), and operate standing (94%), holding suction (89%) and dissector (83%); sometimes the endoscope is held by the primary surgeon (22–24%). The second surgeon usually holds the endoscope (72%) and irrigation (42%). During tumor removal most surgeons stand on the same side (65–66%). Many respondents report strain at the dorsolumbar (50%) or cervical (26%) level. Almost one-third of surgeons incorporate a pause during surgery to stretch, and approximately half exercise to be fit for surgery; 16% had sought medical attention for ergonomic-related symptoms. Conclusion Most respondents value ergonomics in ETS. The variability in surgical set-ups and the relatively high report of complaints underline the need for further studies to optimize ergonomics in ETS.

Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma.A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-RIntra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-RAll the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.

Objectives The role of tumor‐associated neutrophils (TANs) in the nodal spread of cancer cells remains unexplored. The present study evaluates the occurrence and clinical significance of human nodal TANs. Methods The relevance, derivation, phenotype and interactions of nodal TANs were explored via a large immunohistochemical analysis of carcinoma‐draining lymph nodes, and their clinical significance was evaluated on a retrospective cohort of oral squamous cell carcinomas (OSCC). The tumor‐promoting function of nodal TAN was probed in the OSCC TCGA dataset combining TAN and epithelial‐to‐mesenchymal transition (EMT) signatures. Results The pan‐carcinoma screening identified a consistent infiltration (59%) of CD66b+ TANs in tumor‐draining lymph nodes (TDLNs). Microscopic findings, including the occurrence of intra‐lymphatic conjugates of TANs and cancer cells, indicate that TANs migrate through lymphatic vessels. In vitro experiments revealed that OSCC cell lines sustain neutrophil viability and activation via release of GM‐CSF. Moreover, by retrospective analysis, a high CD66b+ TAN density in M‐TDLNs of OSCC (n = 182 patients) predicted a worse prognosis. The analysis of the OSCC‐TCGA dataset unveiled that the expression of a set of neutrophil‐specific genes in the primary tumor (PT) is highly associated with an EMT signature, which predicts nodal spread. Accordingly, in the PT of OSCC cases, CD66b+TANs co‐localised with PDPN+S100A9− EMT‐switched tumor cells in areas of lymphangiogenesis. The pro‐EMT signature is lacking in peripheral blood neutrophils from OSCC patients, suggesting tissue skewing of TANs. Conclusion Our findings are consistent with a novel pro‐tumoral TAN compartment that may promote nodal spread via EMT, through the lymphatics., Our findings propose a novel pro‐tumoral TAN (tumor‐associated neutrophil) compartment with a role in promoting the nodal metastatic colonisation via EMT (epithelial‐to‐mesenchymal transition), through the lymphatic route.