Preoperative Direct Puncture Embolization Using a Nonadhesive Ethylene Vinyl Alcohol (EVOH) Liquid Embolic Agent for Head and Neck Paragangliomas.

PURPOSE: This retrospective study aimed to assess the safety and technical efficacy of preoperative direct puncture embolization using a nonadhesive ethylene vinyl alcohol (EVOH) copolymer-based liquid embolic agent (LEA) combined with balloon occlusion at the origin of the external carotid artery for head and neck paragangliomas (HNP). METHODS: We conducted a review of all consecutive cases of HNPs treated with direct puncture embolization using EVOH-based LEAs between 2017 and 2022 in 2 tertiary high-volume hospitals. RESULTS: A total of 25 cases of HNPs in 24 patients underwent direct puncture embolization (12 males, 12 females, mean age 50.9 ± 15.6 years). The average lesion volume was 299.95 mm3. The mean procedure time was 139.11 min, and the mean volume of EVOHs used per case was 19.38 mL. Successful complete devascularization was achieved in all cases, with a homogeneous and deep penetration of the embolic agent into the tumor vessel bed regardless of the LEA type. CONCLUSION: Preoperative embolization of HNPs using a direct puncture technique and EVOHs is a safe, efficient, and feasible treatment option with a low risk of complications. This procedure facilitates surgery by transforming tumors into avascular masses that are well-delineated against the surrounding normal tissue.

Real-Life Experience in the Management of Sinonasal Complications of Dental Disease or Treatments.

Diagnosis and management of sinonasal complications of dental diseases or treatment (SCDDT) may be challenging. We aimed to report our real-life experience in patients treated with endoscopic endonasal approach describing data about symptoms, etiology, extension of the disease and success rate. We evaluated retrospectively data about 262 patients diagnosed as SCDDT and managed from August 2015 to May 2022. In 44.65% cases, maxillary sinus complications were determined by a dental disorder; the remaining 55.34% of cases were iatrogenic. Patients were managed according to our multidisciplinary protocol including ENT, dental, and radiological evaluation. Treatments were planned with a personalized approach, based on the patient's clinical characteristics; all patients were treated with an endonasal endoscopic mini-invasive conservative approach. Combined dental treatment was performed simultaneously in 152/262 (58%) of patients; in the remaining cases, it was postponed after surgery. The overall treatment success rate (symptom resolution and endoscopically observed maxillary sinus healing) was 96.5%. At 15 days after surgery, we observed a significant improvement in the quality of life. The mean post-operative Sinonasal outcome test-22 (SNOT-22) score was significantly lower compared to baseline (6 versus 43.4; p < 0.05). Our study showed that endoscopic sinus surgery can be a successful procedure for treatment of SCDDT, leading to fast resolution of sinonasal symptoms and improving the quality of life. Furthermore, the technique allows removal of migrated dental material or dental implants even in challenging cases.

Bioradiotherapy with Cetuximab May Reduce the Risk of Neck Node Relapse in Locoregionally Advanced Laryngeal Glottic Carcinoma: May HER1-Profile Be Useful in the Bioselection of Patients?

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed. The two groups were balanced by propensity score method on their baseline characteristics. No significant differences in RFS and OS were found, while MFS results were significantly higher in group A (p = 0.04). Group A showed a 22% reduction in the probability of nodal metastasis (p = 0.0023), mostly in tumors with higher HER1 expression. The salvageability with TL at 3 years was 54% after prior BioRT and 18% after prior upfront NTL (p < 0.05). BioRT with cetuximab showed a reduction in the risk of lymph node relapse, particularly in the case of HER1 positive tumors, and it allowed to achieve a higher rate of functional larynx preservation and a higher salvageability compared with upfront surgery. HER1 analysis could be clinically useful in the bioselection of tumors that may benefit from BioRT with cetuximab, particularly in those with neck node metastatic propensity.

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. METHODS: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. RESULTS: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029). CONCLUSIONS: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

Update of endoscopic classification system of adenoid hypertrophy based on clinical experience on 7621 children.

Introduction: Nasal endoscopy is likely to be the method of choice to evaluate nasal obstruction and adenoid hypertrophy (AH) in children given its excellent diagnostic accuracy and low risk for the patient. The aim of this study was to update the previous classification of AH to guide physicians in choosing the best therapeutic option. Materials and methods: This is a retrospective observational study including 7621 children (3565 females; mean age 5.92; range: 3-14 years) who were managed for adenoid hypertrophy at our institution between 2003 and 2018. All patients were initially treated with medical therapy and then with surgery if not adequately controlled. We performed a specific analysis based on the presence or absence of comorbidities. Results: In 1845 (24.21%) patients, adenoid obstruction was classified as Grade I when the fiberoptic endoscopy showed adenoid tissue occupying < 25% of choanal space. In 2829 of 7621 (37.12%) patients, the adenoid tissue was scored as Grade II since it was confined to the upper half of nasopharynx, with sufficiently pervious choana and visualisation of tube ostium. In 1611 of 7621 (21.14%) cases, adenoid vegetation occupied about 75% of the nasopharynx with partial involvement of tube ostium and considerable obstruction of choanal openings, and was classified as Grade III. Finally, 1336 of 7621 (17.53%) patients were scored as Grade IV due to complete obstruction with adenoid tissue reaching the lower choanal border without allowing the visualisation of the tube ostium. Based on resolution of symptoms in Grade III obstruction after medical therapy (that was mostly seen in patients without comorbidities), we divided patients in two subclasses: Grade IIIA was not associated with comorbidities, while Grade IIIB was correlated with important comorbidities. Conclusions: These results can be useful to guide medical or surgical therapeutic intervention. In patients with class IIIB AH, surgical treatment offered adequate control not only of nasal symptoms but also of associated comorbidities.

Efficacy of Biologics on Refractory Eosinophilic Otitis Media Associated with Bronchial Asthma or Severe Uncontrolled CRSwNP.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: n = 5; Omalizumab: n = 1; Mepolizumab: n = 1; Benralizumab: n = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline (p < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP.

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.

BACKGROUND: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear. METHODS: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination. RESULTS: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively. CONCLUSIONS: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.

Role of Narrow Band Imaging Technology in the Diagnosis and Follow up of Laryngeal Lesions: Assessment of Diagnostic Accuracy and Reliability in a Large Patient Cohort.

BACKGROUND: The aim of this study was to assess diagnostic accuracy and reliability of narrow band imaging (NBI) in the differential diagnosis of laryngeal premalignant lesion, early cancers and recurrences. MATERIAL AND METHODS: We enrolled 231 patients who underwent endoscopic examination with white light endoscopy (WLE) + NBI and divided them into two groups, group A, without previous radiochemotherapy and group B, with previous radiochemotherapy. When indicated, we performed surgical biopsies to evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and likelihood of endoscopic examination comparing WLE alone and WLE + NBI. RESULTS: A positive NBI lesion, compared with a negative NBI lesion, had a 29.68 (group A) and 13.96 (group B) times higher probability to be histologically positive (i.e., confirmed) compared with WLE alone improving the diagnostic accuracy. In group A, the NBI mode showed excellent sensitivity (95.0%), which was higher than WLE 2 mode (77.5%). However, the greatest differences were recorded regarding specificity (96.8% vs. 40.6%). In group B, both NBI alone and WLE + NBI mode showed a 94.1% specificity compared with WLE alone, which had a maximum specificity of 85.3%. The mode comparison between NBI and WLE in both groups showed a statistically significant difference, with p-values <0.0001. CONCLUSIONS: NBI represents a reliable technology in challenging situations, especially in the context of post-radiotherapy or post-surgical mucosal changes showing a high NPV. NBI could reduce the number of unnecessary biopsies related to increased microvascular anomaly revelation, which could help to identify early-stage lesions suitable for minimally invasive surgery and, consequently, decrease hospital admissions.

Predictors of Disease Control After Endoscopic Sinus Surgery Plus Long-Term Local Corticosteroids in CRSwNP.

BACKGROUND: in the era of new biological agents it is important to identify patients who may benefit from conventional therapies such as endoscopic sinus surgery (ESS) plus long-term local corticosteroids from those with patterns of inflammation that are more difficult to control post-operatively and who may benefit from other therapies. OBJECTIVE: determine if preoperative assessment of type and grade of inflammation and clinical factors can predict disease control with ESS plus long-term local corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Eighty patients treated with ESS plus mometasone-furoate 200 µg BID for CRSwNP and followed for at least 1 year were enrolled (November 2017-December 2018) in this prospective observational study. Type and grade of inflammation were evaluated preoperatively by nasal cytology. Based on cellular pattern, patients were grouped as neutrophilic (n = 20), eosinophilic (n = 38), or mixed eosinophil-neutrophilic (n = 22). SNOT-22 and Lund-Kennedy Endoscopic Score were evaluated at baseline and at 3, 6, 9, and 12 months after surgery and used to define disease control. RESULTS: The cumulative probability of remaining free of significant modification of endoscopic score (Lund-Kennedy Endoscopic Score >2) at 3, 6, 9, and 12 months was 0.84, 0.76, 0.71, and 0.68, respectively. At 12-month postoperative evaluation good disease control was observed in 54 of 80 patients (67.5%). Compared to those with good post-operative disease control, those with poor control had a significantly higher pre-operative mean count of eosinophils and neutrophils (p < 0.05). The preoperative inflammatory pattern was associated with relative risk of poor control: neutrophilia (RR: 3.10; CI:1.24-7.71), eosinophilia (RR:8.42; CI:2.72-15.12), and mixed eosinophilic and neutrophilic (RR:25.11; CI:19.41-30.01). We also confirmed that asthma, allergy, blood eosinophilia, and ASA triad could predict poor control. CONCLUSIONS: The type and load of inflammation evaluated preoperatively and selected clinical factors can predict poor control of CRSwNP treated with ESS and local corticosteroids.

The usefulness of the IMAP propeller flap for trachea and tracheostome reconstruction after resection of parastomal recurrence of squamous cell carcinoma following salvage total laryngectomy.

PURPOSE: Parastomal recurrence of squamous cell carcinoma (SCC) with tracheal involvement following salvage total laryngectomy after prior concurrent chemoradiotherapy is one of the most insidious challenges in head and neck surgery because a complex reconstruction is often required for covering a large area of skin loss, filling the dead space beneath, tracheal reconstruction and suspension, and tracheostome resurfacing. The aim is to describe our experience with the internal mammary artery perforator (IMAP) propeller flap for tracheal and tracheostome reconstruction and neck resurfacing after parastomal and cervical trachea resection, especially for suspension and anchoring the stump of the residual distal trachea to the island flap itself. METHODS: We describe IMAP flap reconstruction after resection of parastomal recurrence of SCC requiring cervical trachea resection in five patients between January 1, 2005 and August 30, 2019. RESULTS: IMAP propeller flap was successfully used for reconstruction after complex resection of parastomal recurrence of SCC with cervical trachea involvement in all cases. The mean length and width were, respectively, 16.8 cm (range 13-23) and 6.9 cm (range 5.5-8). We did not report complications of both the donor and the recipient site. Pharyngo-cutaneous or tracheoesophageal fistulas and wound dehiscence were not observed. CONCLUSIONS: to the best of our knowledge, this is the first report about the use of the IMAP propeller flap in this more complex clinical setting and we provide the message that this surgical procedure is worthy of consideration.

Efficacy and long-term follow-up of positional therapy by vibrotactile neck-based device in the management of positional OSA.

STUDY OBJECTIVES: Different therapeutic strategies have been investigated for the treatment of positional obstructive sleep apnea, but more evidence is needed about efficacy and compliance. The objective of this study was to describe the efficacy of vibrotactile neck-based treatment in patients with positional obstructive sleep apnea with different degrees of obstructive sleep apnea severity who were followed for 6 months. METHODS: This is a retrospective study including 162 patients with positional obstructive sleep apnea undergoing vibrotactile neck-based positional therapy. We compared polysomnographic data obtained at baseline and during positional therapy after 1 month. We performed a subgroup analysis based on obstructive sleep apnea severity. Furthermore, we analyzed follow-up data in 84/162 (51.8%) patients with particular focus on discontinuation and complications related to the device. RESULTS: We observed a significant difference between mean baseline obstructive apnea-hypopnea index (OAHI; 21.9 ± 9.9 events/h) and during positional therapy (12 ± 9.2 events/h; P < .01). Moreover, 87/162 (54.9%) patients showed a reduced baseline OAHI of at least 50% and 38/162 (23.4%) achieved complete disease control (OAHI < 5 events/h). At subgroup analysis, at least 50% reduction from baseline OAHI was observed in 56.8% of patients with mild, 55% with moderate, and 47.4% with severe OAHI, whereas complete control of disease was achieved in 50% of patients with mild, 22.5% with moderate, and 7.9% with severe OAHI. At a 6-month follow-up, only 35/84 patients (41.6%) were regularly using the device, with a mean of 5.9 ± 1.2 days per week. CONCLUSIONS: Our results on the efficacy and long-term adherence to vibrotactile neck-based positional therapy showed that positional therapy can be an efficient first-line treatment option for mild positional obstructive sleep apnea and in selected cases of moderate disease. Long-term compliance is limited because of complications and low satisfaction in some patients.

Narrow Band Imaging for lingual tonsil hypertrophy and inflammation, in laryngo-pharyngeal reflux disease.

PURPOSE: The objective of this study is to analyse the relationship between the endoscopic signs of laryngo-pharyngeal reflux, the lingual tonsil hypertrophy (LTH) and its inflammation, adopting Narrow Band Imaging (NBI) technology. METHODS: We enrolled, as cases, patients with clinical diagnosis of laryngopharyngeal reflux disease (LPRD), a Reflux Symptom Index (RSI) ≥ 13, and a Reflux Finding Score (RFS) ≥ 7. Controls were enrolled among patients who underwent the same transnasal endoscopy, equipped with NBI, with a RSI < 13 and a RFS < 7. Nasopharynx, Lingual Tonsils (LT), Hypopharynx and Larynx were evaluated by two experienced otolaryngologists, who calculated the Reflux Finding Scale (RFS) score and focused their attention on the base of the tongue, observing its surface with NBI technology. RESULTS: 82 patients with diagnosis of laryngopharyngeal reflux were enrolled as cases. Mean RFS was 11.7 (SD = 2.9). As controls, we enrolled 80 patients. Mean RFS was 2.7 (SD = 1.63). We found that RFS positivity was associated with a significant increase in LT dimension (2.5 vs 1.1, p < 0.001), with a higher LT crypt inflammation grading (1.8 vs 0.09, p < 0.001) and with a higher Roman Cobblestone pattern grading (1.48 vs 0.11, p < 0.001). A significant correlation between the crypt inflammation and the hyperemia subscore of RFS was present (r = 0.696, p < 0.0001), while it was not possible to find a correlation between crypt inflammation and either diffuse laryngeal edema (r = 0.166, p = 0.135) and posterior commissure hypertrophy (r = 0.089, p = 0.427). CONCLUSIONS: NBI allowed us to identify endoscopically the presence of enlarged lingual tonsil, crypt inflammation and superficial mucosal changes, in patients affected by LPRD. LEVEL OF EVIDENCE: 2 (prospective, case-control study).