Effectiveness of dupilumab versus endoscopic sinus surgery for the treatment of type-2 chronic rhinosinusitis with nasal polyps: a preliminary report.

PURPOSE: Historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS), type-2 Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) treatment was revolutionized by the introduction of dupilumab but universally accepted guidelines are still lacking. METHODS: Patients treated at our University Hospital for type-2 CRSwNP were enrolled. Demographic data were collected, as well as laboratory (eosinophils, total IgE), endoscopic [nasal polyps score (NPS), modified Lund-Kennedy score (mLKS)], radiological [Lund-Mackay score (LMS) at CT scan], SNOT-22, and olfactory [Sniffin' Sticks identification test (SSIT)] features. Patients were treated with dupilumab or ESS and re-evaluated after 3 and 12 months. RESULTS: At 3 and 12 months, patients undergoing ESS achieved a higher reduction of NPS and mLKS, while patients receiving dupilumab experienced a higher improvement at SNOT-22 and SSIT with a greater positive variation in the prevalence of anosmia (- 57.7% vs - 42.9%) and normosmia (+ 37.8 vs + 28.5%). Mean mLKS and LMS were quite similar. Results were independent of clinical features known to contribute to CRSwNP severity, except for patients with ≥ 2 prior ESS who had a significantly lower smell improvement. CONCLUSION: ESS and dupilumab were effective at reducing CRSwNP inflammatory burning. CRSwNP smell impairment cannot be attributed only to olfactory cleft obstruction and other mechanisms may be involved. Dupilumab acts systemically with poor correlation with NPS. As of today, dupilumab appears to be more suitable for elderly patients with anesthesiological contraindications and/or several previous surgeries, while ESS may represent the first-line choice in surgery-naive patients.

Diagnostic therapeutic assistance pathway (PDTA) of type 2 chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a complex and heterogeneous disorder whose etiopathogenetic picture is not yet completely known and is classically divided into CRS with (CRSwNP) and without nasal polyps (CRSsNP). But today the distinction is made with type 2 and nontype 2 variants. A rational and defined pathway for the diagnosis of chronic rhinosinusitis is an indispensable means to be able to arrive at a correct identification of the patient. This typing is essential to be able to arrive at the correct course of treatment, which turns out to be different for different types of patients. For this reason, the realization of a diagnostic therapeutic pathway represents a fundamental way for the otolaryngologist specialist but not only, since today diagnostics has a multidisciplinary framework. In the present work, precise indications have been developed to arrive at a correct diagnosis. The various diagnostic pathways and processes to arrive at a correct therapeutic framing have been highlighted. Therapy ranging from medical therapy to surgical therapy without neglecting the new biological therapies. It does not represent a guideline but a diagnostic method that can be adapted to all the various territorial realities.

Blood CD62Llow inflammatory eosinophils are related to the severity of asthma and reduced by mepolizumab.

BACKGROUND: Eosinophils have been divided into different subpopulations with distinct phenotypes based on CD62L expression. No data are available regarding the correlation between eosinophils subphenotypes and clinical severity of asthma, as well as the effect of anti-IL-5 therapy on these cells. The study investigates the correlation between blood CD62Llow inflammatory eosinophils (iEos) and clinical severity of severe eosinophilic asthma (SEA) and evaluates the impact of mepolizumab on iEos. METHODS: 112 patients were screened and were divided in two groups: biological-naive (n = 51) and biological-treated patients (n = 61). The Biological-naive patients were analyzed before treatment (Group A) and 19 out of 51 patients, were longitudinally analyzed before and after treatment with mepolizumab 100 mg s.c/4 weeks (Group B); 32 patients were excluded because they were being treated with other biological therapies. Blood eosinophils were analyzed by FACS and correlated with clinical scores. In vitro effect of IL-5 and mepolizumab on CD62L expression was assessed. RESULTS: A significant correlation between blood CD62Llow cells and clinical scores of asthma and nasal polyps, as well as the number of asthma exacerbations in the last year was shown in untreated patients. In longitudinally studied patients we observed a marked reduction of CD62Llow cells paralleled by an increase in the proportion of CD62Lbright cells, associated with clinical improvement of asthma control. In vitro, CD62L expression on eosinophils is modulated by IL-5 and anti-IL-5. CONCLUSION: A positive correlation between CD62Llow iEos and the baseline clinical features of SEA with CRSwNP was shown. Furthermore mepolizumab restores the healthy balance among eosinophils sub-phenotypes in SEA patients.

Sinonasal nodular fasciitis: report of a case with USP6 rearrangement.

Nodular fasciitis (NF) is a benign myofibroblastic proliferation characterized by rapid growth, a self-limiting course, and USP6 gene rearrangement. Although it can arise in the head and neck region, very few cases of NF involving the sinonasal tract have been reported to date. Herein we report a case of NF involving the nasal cavity presenting as a polypoid well-defined mass causing obstructive symptoms in a male with a history of multiple local surgeries. Although the mass had an unusual clinical presentation, the histopathologic and immunohistochemical findings were consistent with NF. Fluorescent in situ hybridization performed with break-apart probes flanking the USP6 locus on chromosome 17p13 revealed the presence of USP6 gene rearrangement. The patient remained free of disease 124 months after surgical treatment. Considering its remarkably benign behavior despite its alarming clinical and histologic features, the distinction of NF from sinonasal malignant tumors is essential.

Radiomics-Based Analysis in the Prediction of Occult Lymph Node Metastases in Patients with Oral Cancer: A Systematic Review.

BACKGROUND: Tumor extension and metastatic cervical lymph nodes' (LNs) number and dimensions are major prognostic factors in patients with oral squamous cell carcinoma (OSCC). Radiomics-based models are being integrated into clinical practice in the prediction of LN status prior to surgery in order to optimize the treatment, yet their value is still debated. METHODS: A systematic review of the literature was conducted according to the PRISMA guideline. Baseline study characteristics, and methodological items were extracted and summarized. RESULTS: A total of 10 retrospective studies were included into the present study, each of them exploiting a single imaging modality. Data from a cohort of 1489 patients were analyzed: the highest AUC value was 99.5%, ACC ranges from 68% to 97.5%, and sensibility and specificity were over 0.65 and 0.70, respectively. CONCLUSION: Radiomics may be a noninvasive tool to predict occult LN metastases (LNM) in OSCC patients prior to treatment; further prospective studies are warranted to create a reproducible and reliable method for the detection of LNM in OSCC.

Dental impression silicone putty in transoral laser laryngeal surgery: prevention of oral complications.

Objective: To describe a new method to improve the exposure of the surgical field and to protect the oral cavity during transoral laser micro-surgery (TOLMS) of the larynx. Methods: Dental Impression Silicone Putty (DISP) was employed as an alternative to traditional mouthguards. Results: DISP mouthguards perfectly fit to each patient, reduce encumbrance in the mouth, and reduce pressure on the teeth; disadvantages are minimal. Conclusions: Although clinical studies are necessary to demonstrate the efficacy of the method in reducing the incidence of oral complications, DISP mouthguards represent a significant aid for laryngeal exposure.

Endoscopy-assisted transoral approach for parapharyngeal space tumors: Our experience and a systematic review of the literature.

Background: Several approaches have been described for the excision of parapharyngeal space tumors (PPSTs). Advances in endoscopy gave a further stimulus to the use of the transoral route. Aims: We present our experience with the endoscopy-assisted transoral approach (EATA) in this regard and a review of the most recent literature about EATA for PPSTs excision. Materials and Methods: We retrospectively analyzed our experience and systematically reviewed the literature about the outcomes of this technique. Results: Seven PPSTs were completely excised, with three of them requiring a combined transcervical approach. Only one case of postoperative wound dehiscence was registered, and the mean length of stay was 3.9 days. Final histopathological examination confirmed the results obtained with preoperative fine-needle aspiration biopsy in all cases and no recurrences were apparent after a mean follow-up of 28.1 months. Discussion: Magnetic resonance imaging, the modified Mallampati score and the 8 Ts criteria are useful instruments for the choice of the most appropriate surgical approach. Conclusion: In light of our experience and following other published series in the literature, we believe that EATA may represent a safe and effective approach for the treatment of the majority of PPSTs.

The Same-Up-Down Staging System for Recurrent Early Glottic Cancer.

(1) Background: The treatment of recurrent early glottic cancer (rEGC) remains challenging. We wanted to investigate how the oncological outcomes are affected by the initial and recurrent stages, in order to propose our newly developed Same-Up-Down (SUD) staging system. (2) Methods: In our cohort of 258 rEGC patients, we retrospectively assessed the prognostic performances of the rTNM (the TNM staging system for recurrence), CLRSS, CLRSS-2, and SUD staging systems by univariate and multivariate Cox analysis, comparing their predictive capability using Harrell's C-index. (3) Results: The SUD classification satisfactorily predicted both overall survival (p = 0.022) and second-recurrence-free survival (p = 0.024, as same + down vs. upstage) in our cohort. It also outperformed the other three systems in terms of prediction of survival, with an improvement of 1.52%, 1.18%, and 3.96% in the predictive capacity of overall survival, disease-specific survival, and second-recurrence-free survival, respectively. (4) Conclusions: The SUD staging system can efficiently predict survival in rEGC patients, whose prognosis heavily depends on both the initial and recurrent locoregional extension.

Oncological and functional impact of adjuvant treatments after open partial laryngeal surgery: a systematic review of the literature and a meta-analysis.

BACKGROUND: The oncological and functional role of postoperative radiotherapy (PORT) after open partial laryngeal surgery (OPLS) remains debatable. METHODS: A systematic review and a meta-analysis of the literature were conducted according to the PRISMA guidelines. Outcomes of patients receiving OPLS with and without PORT for laryngeal cancer were summarized. RESULTS: In the 10 studies that were included in the meta-analysis, no significant difference emerged in terms of pooled overall survival between OPLS patients who did and who did not receive PORT (- 0.3%, 95% CI - 5.4 to 4.9%, p = 0.922). Only one study showed a significantly higher incidence of complications in the PORT cohort. CONCLUSIONS: PORT may apparently be performed after OPLS in face of adverse postoperative features without an increased risk of toxicities affecting the neolarynx. Because of the limitations in the available literature, the oncological and functional effects of PORT in this setting needs to be prospectively assessed to strengthen the evidence of this treatment strategy for laryngeal cancer.

Otoendoscopy in the era of narrow-band imaging: a pictorial review.

PURPOSE: Otoendoscopy represents the initial non-invasive diagnostic cornerstone for external and middle ear disorders. Recently, new techniques of enhanced imaging such as narrow-band imaging (NBI) have been introduced but their role as a potential aid in otological practice remains unproven. In this pictorial review, we want to present the potential application of this endoscopic method, highlight its limitations, and give some hints regarding its future implementation. METHODS: Representative cases of external and/or middle ear pathologies were selected to illustrate the role of NBI in this regard. RESULTS: NBI may represent a useful aid in the otological work-up, in the differential diagnosis of ear tumor-like masses, and, possibly, in the prognosis of tympanic perforations. For other ear disorders, instead, this technique does not seem to add anything to the standard clinical practice. CONCLUSIONS: NBI might prove useful in the assessment of selected external and middle ear disorders but its role must be prospectively validated.

A 5-year experience with midline catheters in the management of major head and neck surgery patients.

BACKGROUND: In the perioperative management of major head and neck surgery (HNS) patients, the performance of midline catheters (MCs) has been never tested. We present here our 5-year experience by reporting MC-related complications and by identifying the preoperative risk factors associated with their development. METHODS: Clinical variables were extracted and the dwell time, the number, and the type of postprocedural complications of MCs were retrieved. Complications were classified into major (needing MCs removal and including catheter-related bloodstream infection or deep vein thrombosis or catheter occlusion) and into minor (accidental dislodgement, leaking, etc.). Descriptive statistics and logistic regression models were used in order to identify the predictors of complications. RESULTS: A total of 265 patients were included, with a mean age of 67.4 years. Intraprocedural complications occurred in 1.1% of cases, while postprocedural complications occurred in 13.9% of cases (12.05/1000 days), but they were minor in more than 7.0% (5.4/1000 catheter-days). There were 19 minor complications (7.1% or 5.4/1000 catheter-days) while 18 (7%, 5.1/1000 catheter-days) patients experienced at least one major complication. Female sex (OR = 1.963, 95% CI 1.017-3.792), insertion in the right arm (OR = 2.473, 95% CI 1.150-5.318), and an ACE-27 score >1 (OR = 2.573, 95% CI 1.295-5.110) were independent predictors of major complications. CONCLUSIONS: MCs appear to represent an effective option in the setting of major HNS. The identification of patients most at risk for MC-related complications should prompt a postoperative watchful evaluation.

Rhino-oropharingeal osteoradionecrotic soft-tissue and bony defect reconstruction with submental artery island flap: a case report.

BACKGROUND: The submental artery island flap is widely used in head and neck reconstruction, since it is easy and quick to harvest, and it can be successfully used for the coverage of perioral, intraoral and facial defects. We used this technique for the reconstruction of a complex soft-tissue and bony defect of rhino-oropharinx. CASE REPORT: Osteoradionecrosis of rhino-oropharingeal posterior wall with C2 necrotic body exposure occurred in a 77-year-old woman. After the failure of reconstruction with a Hadad-Bassagasteguy flap, a submental island flap with cervical spine stabilization was planned to be performed in a one-stage operation. The anterior arc of C1 and odontoid process of C2 were removed and, according to the defect size, a submental island flap was designed in an elliptical fashion. The flap was rotated 180° and tunnelized under the left parapharingeal-prevertebral space, then it was positioned in the rhino-oropharinx and fixed with reabsorbable sutures. The donor site was closed primarily. No peri- or post-operative complications occurred, neither in the recipient nor in the donor-site. At the latest follow-up, 15 months postoperatively, the patient was able to speak without any impairment and started swallowing rehabilitation with good results and an aesthetically satisfactory outcome. CONCLUSION: The submental island flap may be a reliable and versatile flap for reconstruction of head and neck defects, even though in the rhino-oropharingeal posterior wall.

High proportion of inflammatory CD62Llow eosinophils in blood and nasal polyps of severe asthma patients.

BACKGROUND: In mice models, eosinophils have been divided into different subpopulations with distinct phenotypes and functions, based on CD62L and CD101 patterns of membrane expression. Limited data are available in humans. OBJECTIVE: To investigate eosinophils subpopulations in peripheral blood (PB) and nasal polyp tissue (NP) from severe eosinophilic asthma (SEA) patients plus concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: We recruited 23 SEA patients (14 with CRSwNP); as controls, we enrolled 15 non-severe asthma patients, 15 allergic rhinitis patients without asthma and 15 healthy donors. Eosinophils were isolated from PB and NP and analysed by FACS. Eotaxin-3 and eotaxin-1 mRNA expression in NP tissue was also evaluated. RESULTS: A significantly higher percentage of circulating CD62Llow cells was observed in SEA, as compared with controls, expressing higher levels of CCR3, CD69 and lower levels of CD125 (IL-5R), CRTH2, CD86 and CD28 in comparison with CD62Lbright cells. In NP, eosinophils showed a high proportion of CD62Llow phenotype, significantly greater than that observed in PB. Surface expression of IL-3R, IL-5R, CD69 and CD86 was significantly higher in CD62Llow eosinophils from NP than in those from blood. Moreover, eotaxin-3 mRNA expression positively correlated with the percentage of CD62Llow cells in NP. CONCLUSION: Two different eosinophil subphenotypes can be identified in blood and NP of SEA patients, with a preferential accumulation of CD62Llow inflammatory cells in NP.

Low levels of miR-34c in nasal washings as a candidate marker of aggressive disease in wood and leather exposed workers with sinonasal intestinal-type adenocarcinomas (ITACs).

INTRODUCTION: Sinonasal intestinal-type adenocarcinomas (ITACs) are rare and aggressive tumors, closely related to professional exposure to wood dusts or leather. Here we explored the role of non-coding RNAs controlling MUC2 in liquid biopsies and tumors from ITAC patients with the aim of identifying biomarkers and molecular mechanisms to improve early diagnosis, prognosis, and therapeutic approaches for this rare cancer. METHODS: MiR-34c-3p, lncRNA AF147447 and MUC2 were measured in tumors and normal mucosa, in nasal washings (NW) from the affected and non-affected nostril and in plasma from 17 ITAC patients. The Apparent Diffusion Coefficient (ADC) was also evaluated by Magnetic Resonance Imaging. RESULTS: MiR-34c was higher in ITACs compared to the corresponding normal mucosa (p = 0.021). Differentiated tumors exhibited higher miR-34c levels (p = 0.025) and lower ADC values (p<0.001) compared to mucinous ones and these parameters were also inversely correlated (r = 0.87; p = 0.001). High MUC2 tumor expression was associated with orbital extension (p = 0.010). Low miR-34c levels in NW were associated with orbital (p = 0.009) and intracranial (p = 0.031) extension and with advanced TNM stage (p = 0.054). Functional analysis identified Wnt, Focal adhesion, MAPK and inflammatory signalings among the pathways most enriched in mir-34c targets. DISCUSSION: Our results suggest measuring miR-34c in NW as a biomarker for early diagnosis and monitoring of ITAC patients and for the surveillance of wood and leather exposed workers. Further research on the involvement of miR-34c regulated pathways in ITAC tumorigenesis may also allow the development of new therapeutic approaches for this rare cancer.

A practical overview of CT and MRI features of developmental, inflammatory, and neoplastic lesions of the sphenoid body and clivus.

The sphenoid bone is an unpaired bone that contributes to the formation of the skull base. Despite the enormous progress in transnasal endoscopic visualisation, imaging techniques remain the cornerstones to characterise any pathological condition arising in this area. In the present review, we offer a bird's-eye view of the developmental, inflammatory, and neoplastic alterations affecting the sphenoid body and clivus, with the aim to propose a practical diagnostic aid for radiologists based on clinico-epidemiological, computed tomography, and magnetic resonance imaging features.

Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature.

X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such as Pneumocystis jirovecii pneumonia, biliary tract disease due to Cryptosporidium parvum, and malignancy. We report a 41-year-old male presenting with recurrent leishmaniasis, hypogammaglobulinemia, and myopathy. Whole-exome sequencing (WES) identified a missense variant in the CD40LG gene (c.107T>A, p.M36K), involving the transmembrane domain of the protein and a missense variant in the carnitine palmitoyl-transferase II (CPT2; c.593C>G; p.S198C) gene, leading to the diagnosis of hypomorphic XHIGM and CPT2 deficiency stress-induced myopathy. A review of all the previously reported cases of XHIGM with variants in the transmembrane domain showcased that these patients could present with atypical clinical features. Variants in the transmembrane domain of CD40LG act as hypomorphic generating a protein with a lower surface expression. Unlike large deletions or extracellular domain variants, they do not abolish the interaction with CD40, therefore preserving some biological activity.

Extracellular vesicles miR-210 as a potential biomarker for diagnosis and survival prediction of oral squamous cell carcinoma patients.

BACKGROUND: The identification of early diagnostic and prognostic biomarkers in oral squamous cell carcinoma (OSCC) is an unmet clinical need. We hypothesized that extracellular vesicles miR-210 expression (EV-miR-210) could be a potential biomarker for OSCC diagnosis and follow-up. METHODS: The expression of EV-miR-210 was measured in the plasma of OSCC patients (n = 30) and compared to that of controls (n = 14). RESULTS: The median EV-miR-210 expression was significantly higher in OSCC patients compared to controls who had often, undetectable levels (p < 0.0001). We performed receiver operating characteristic (ROC) analysis for discriminating OSCC cases from controls. EV-miR-210 yielded an area under the curve (AUC) of 0.9513 with sensitivity 92.3% and specificity 86.6%. Kaplan-Meier curves indicated that high EV-miR-210 expression was associated with worse 3 years' survival (p < 0.05). Cox regression hazard model indicated that high EV-miR-210, G2, and G3 grading and pathological nodal status (pN)>1 were independent predictors of worse survival in OSCC patients. CONCLUSION: These preliminary data suggest that EV-mir-210 may be a novel diagnostic and prognostic biomarker in OSCC.