Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature.

INTRODUCTION: The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. MATERIALS AND METHODS: A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. RESULTS: 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. CONCLUSION: Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.

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.

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.

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.

The Histological Background of Recurrence in Laryngeal Squamous Cell Carcinoma: An Insight into the Modifications of Tumor Microenvironment.

Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels. Postradiotherapy recurrent/persistent laryngeal squamous cell carcinoma typically presents a discohesive growth pattern within a fibrotic background associated with significant changes of the tumor immune microenvironment, with both important immunosuppressive and immunostimulatory effects. Overall, the increase of immunoregulatory cells and immune checkpoints such as CTLA-4, TIM-3, PD-1, and PD-L1 induced by radiotherapy and chemotherapy strongly supports the use of immune checkpoint inhibitors in recurrent/persistent laryngeal carcinoma. Future studies aiming to identify predictive factors of the response to immune checkpoint inhibitors should consider such treatment-induced modifications.

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.

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.

Post-diagnosis smoking cessation and survival of patients with head and neck cancer: a systematic review and meta-analysis.

Cigarette smoking is the main risk factor for head and neck cancer (HNC) and many HNC patients are active smokers at diagnosis. We conducted a systematic literature review and meta-analysis to quantify the survival impact of smoking cessation at or around the time of HNC diagnosis. We searched studies published until December 31, 2021, and used random-effects meta-analysis to pool study-specific estimates into summary hazard ratio (SHR) and corresponding 95% confidence intervals (CI). Sixteen studies were published between 1983 and 2021, and over 2300 HNC patients were included. Studies were diverse in terms of design, patients, tumours and treatment characteristics, and criteria used to discriminate quitters from continued smokers. HNC patients who quit smoking at or around diagnosis had significantly better overall survival than continued smokers (SHR 0.80, 95% CI 0.70-0.91, n studies = 10). A beneficial effect of post-diagnosis smoking cessation was suggested for other survival endpoints as well, but the results were based on fewer studies (n = 5) and affected by publication bias. Cessation counselling should be offered to all smokers who start a diagnostic workup for HNC and should be considered standard multidisciplinary oncological care for HNC patients. PROSPERO registration number CRD42021245560.

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.

Current outcomes of myringoplasty in a European referral children's hospital.

OBJECTIVES: Myringoplasty is a frequently performed procedure in children, with a heterogeneous failure rate. Our study aimed to evaluate the outcome of myringoplasty in a pediatric hospital and to identify which are risk factors for reperforation or poor hearing improvement after surgery. METHODS: Preoperative and intraoperative variables between pediatric patients who had undergone myringoplasty with an intact tympanic membrane at follow-up and the cases with reperforation were compared. The same factors were investigated as potential predictors of audiological success. Pre and postoperative PTA and ABG were compared in the whole population, in structural success and failure groups and closure of ABG was calculated and used to compare the audiological outcomes between the two groups. RESULTS: Parameters that affected the postoperative integrity of TM were age, the time between diagnosis and surgery, the intraoperative status of the middle ear, and secondhand smoke exposure. Early perforations occurred mostly after surgeries performed by trainees, while late perforations were more frequently in autumn. Myringoplasty, regardless of the structural outcome, can improve the ABG and PTA. No preoperative and intraoperative parameters affected the audiological outcome. CONCLUSION: Pediatric myringoplasty is a safe and successful procedure that can improve hearing, regardless of the structural outcome. In light of our results, parameters to consider before surgery are age, the time between diagnosis and surgery, the intraoperative status of the middle ear, and secondhand smoke exposure.

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.

The Many Faces of Head and Neck Surgery in 2022 and Looking Ahead!

Head and neck (HN) cancer, which mainly presents in the form of squamous cell carcinoma, was the seventh most common cancer worldwide in 2018, with approximately 890,000 new cases and 450,000 deaths [...].

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.