Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

Elective neck irradiation in the management of esthesioneuroblastoma: a systematic review and meta-analysis.

BACKGROUND: There is no consensus about the optimal management of the neck in clinically node negative esthesioneuroblastoma (ENB). The aim of this study is to assess the impact of elective neck irradiation (ENI) in terms of regional disease control and survival. METHODS: The study was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, and Google Scholar databases. The primary outcome was the regional recurrence rate (RRR), that was reported as odds ratio (OR) and 95% confidence interval (CI). Secondary outcomes were the overall survival (OS), and the distant-metastases free survival (DMFS), that were reported as logarithm of the hazard ratios (logHRs) and 95% confidence intervals (CIs). RESULTS: A total of 489 clinically node negative patients were included from 9 retrospective studies. ENI significantly reduced the risk of regional recurrence compared to no treatment. No difference was measured between ENI and observation, according to both OS and DMFS. No stratified analysis could be performed based on Kadish stage and Hyams grade. CONCLUSIONS: ENI should be recommended to improve the regional disease control. No advantage was measured in terms of survival or distant metastases with a low quality of evidence. Further prospective studies should be designed to understand if ENI could be avoided in early stage and low-grade tumors.

Teaching parotid surgery to ENT residents in the era of new technologies: an ex-vivo ovine model.

Surgical training has recently assumed a central role in the otolaryngology field, and the necessity to train residents and fellows' skills in a progressive manner has led to an incredible widespread of ex-vivo animal models for several surgical procedures. To report our experience with an ex-vivo ovine model for parotid gland dissection in a training context. A junior resident (PGY-1) and a post-graduate student with no experience in parotid surgery were guided by a skilled surgeon in the parotid gland dissection for each step of the procedure. Three different adult lamb heads were used for this feasibility study. A specific preparation of the model was performed before the training session. Similarity between the ovine model and the human were recorded. The resident and the post-graduate student were able to carry out a complete parotid gland dissection under supervision. The correct identification of surgical landmarks has led to a proper surgical simulation. The facial nerve dissection was adequately performed, and all branches were isolated. Parotid surgery training on an ex-vivo ovine model is useful, easy repeatable, and low cost. The ovine model presented in this study has similarities in size, structure, and tissue consistence to the human parotid, making it an ideal model for residents to simulate parotid surgery.

Lateral conservative approach for recurrent/persistent hypopharyngeal carcinoma: a case series.

PURPOSE: Early persistent/recurrent hypopharyngeal tumours represent a challenge for surgeons who have to balance the need for oncological radicality and the desire to maintain a functioning larynx with preservation of the patient's quality of life. The aim of this study was primarily to understand the technical feasibility, functional outcomes, and the possibility of obtaining oncological radicality using lateral hypopharyngectomy with laryngeal preservation in early recurrent post-radio/(chemo)therapy hypopharyngeal tumours. METHODS: Patients with recurrent T1 hypopharyngeal squamous cell carcinoma were retrospectively selected from our institutional database. The external lateral approach according to Spriano and a modified lateral hypopharyngectomy with laryngeal preservation were used to resect tumours of the lateral pyriform sinus wall. Reconstruction was obtained by direct approximation of the posterior border of the sectioned thyroid cartilage to the posterior hypopharyngeal wall, and this was reinforced with a second layer of vascularised and non-irradiated tissue that was provided by a microvascular fascial anterobrachial flap. Swallowing was assessed 3 weeks after surgery using videoendoscopic evaluation. RESULTS: The surgical procedure was technically feasible, and complete resection was obtained in all patients. None of the patients experienced major post-operative complications (salivary fistula, bleeding, aspiration pneumonia). Mild dysphagia was observed in one patient who underwent swallowing rehabilitation. Tracheostomy was closed in all patients. No recurrence was recorded after a median follow-up of 20 months. CONCLUSION: The reported experience shows that, in selected cases, it is possible to radically remove lateral hypopharyngeal cancer with acceptable functional results.

Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients.

BACKGROUND: TP53 mutation is associated with decreased survival rate in head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify microRNAs (miRNAs) whose expression associates with TP53 mutation and survival in HNSCC. PATIENTS AND METHODS: We analyzed TP53 status by direct sequencing of exons 2 through 11 of a prospective series of 121 HNSCC samples and assessed its association with outcome in 109 followed-up patients. We carried out miRNA expression profiling on 121 HNSCC samples and 66 normal counterparts. miRNA associations with TP53 mutations and outcome were evaluated. RESULTS: A TP53 mutation was present in 58% of the tumors and TP53 mutations were significantly associated with a shorter recurrence-free survival. This association was stronger in the clinical subgroup of patients subjected to adjuvant therapy after surgery. The expression of 49 miRNAs was significantly associated with TP53 status. Among these 49, we identified a group of 12 miRNAs whose expression correlates with recurrence-free survival and a group of 4 miRNAs that correlates with cancer-specific survival. The two groups share three miRNAs. Importantly, miRNAs that correlate with survival are independent prognostic factors either when considered individually or as signatures. CONCLUSIONS: miRNAs expression associates with TP53 status and with reduced survival after surgical treatment of squamous cell carcinoma of the head and neck.

Comparison between the high-definition 3D exoscope and the operating microscope in head and neck reconstruction.

The purpose of this study was to compare the three-dimensional (3D) operating exoscope (OE) with the conventional operating microscope (OM) in head and neck reconstruction. A retrospective cohort study was performed including 50 consecutive patients with no history of previous surgery or irradiation (32 male, 18 female; mean age 59.2 ± 13.3 years), who underwent free flap head and neck reconstruction using a 3D OE (n = 25; OE group) or conventional OM (n = 25; OM group). The mean total operative time was 8.0 ± 1.53 h in the OE group and 7.6 ± 1.52 h in the OM group (P = 0.86). The median (interquartile range) anastomosis time was 78.0 (63.0-91.5) minutes in the OE group and 90.0 (75.5-115.0) minutes in the OM group (P = 0.06). The final free flap survival rate was 100%. Only seven patients experienced a free flap reconstruction-related complication, and they were similarly distributed between the two groups (four in the OE group, three in the OM group; P = 0.68). Secondary outcomes (length of hospital stay, tracheostomy dependence, feeding tube dependence) were comparable in the two groups (P > 0.05). The 3D OE is a viable alternative to the conventional OM for performing standard head and neck free flap reconstructive procedures.

Infrahyoid myocutaneous flap in head and neck reconstruction: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to analyse the literature on the infrahyoid myocutaneous flap (IHMCF) and evaluate its clinical outcomes. The MEDLINE, Embase, Web of Science, Cochrane Library, and Scopus databases were searched (inception to December 31, 2021). Meta-analyses were then conducted to estimate the overall rates of partial flap loss, total flap loss, salivary fistula, and surgical revision. The 21 studies that met the inclusion criteria included 768 patients undergoing head and neck reconstruction with 773 IHMCF. The oral cavity (77.7%) and oropharynx (13.0%) were the most reconstructed sites. The meta-analyses estimated a pooled partial flap loss rate of 10.4% (99% confidence interval (CI) 5.4-16.7%), total loss rate of 1.8% (99% CI 0.8-3.2%), salivary fistula rate of 3.0% (99% CI 1.3-5.3%), and surgical revision rate of 1.9% (99% CI 0.7-3.7%). Fast flap harvesting and low donor site morbidity were other flap features. Previous thyroid surgery or neck dissection and advanced lymph nodal stage were considered contraindications to IHMCF reconstruction by most authors, while prior neck radiotherapy was reported as a relative contraindication. This pedicled cervical flap is a versatile and reliable reconstructive option for medium-sized head and neck defects. Careful preoperative assessment of the neck condition allows for its safe use.

Metastasis-directed stereotactic body radiation therapy in the management of oligometastatic head and neck cancer.

INTRODUCTION: Recently major efforts have been made to define the oligometastatic setting, but for head and neck cancer (HNC) limited data are available. We aimed to evaluate outcome of oligometastatic HNC treated with Stereotactic body radiotherapy (SBRT) as metastasis-directed therapy. MATERIALS AND METHODS: We analyzed patients treated with SBRT on a maximum of five oligometastases from HNC, in up to two organs. Concomitant treatment was allowed. End points were toxicity, local control of treated metastases (LC), progression-free survival (PFS) and overall survival (OS). RESULTS: 48 consecutive patients and 71 lesions were treated. With a follow-up of 20.2 months, most common primary tumors were larynx (29.2%) and salivary glands (29.2%), while common site of metastases was lung (59.1%). Median dose was 48 Gy (21-75) in 3-8 fractions. Treatment was well tolerated, with two patients reporting mild pain and nausea. LC rates at 1 and 2 years were 83.1% and 70.2%. Previous local therapy (HR 4.97; p = 0.002), oligoprogression (HR 4.07; p = 0.031) and untreated metastases (HR 4.19; p = 0.027) were associated with worse LC. PFS at 1 and 2 years were 42.2% and 20.0%. Increasing age (HR 1.03; p = 0.010), non-adenoid cystic carcinoma (HR 2.57; p = 0.034) and non-lung metastases (HR 2.20; p = 0.025) were associated with worse PFS. One- and 2-years OS were 81.0% and 67.1%. Worse performance status (HR 2.91; p = 0.049), non-salivary primary (HR 19.9; p = 0.005), non-lung metastases (HR 2.96; p = 0.040) were correlated with inferior OS. CONCLUSIONS: SBRT can be considered a safe metastasis-directed therapy in oligometastatic HNC. Efficacy of the treatment seems to be higher when administered upfront in the management of metastatic disease; however, selection of patients need to be improved due to the relevant risk of appearance of new metastatic site after SBRT.

Free flap microvascular anastomosis in head and neck reconstruction using a 4K three-dimensional exoscope system (VITOM 3D).

The aim of this study was to evaluate the feasibility of microvascular anastomosis using a 4K three-dimensional exoscope system (VITOM 3D) in 10 consecutive cases of free flap head and neck reconstructive surgery. This was a clinical human study of free flap microvascular anastomosis using a VITOM 3D exoscope in 10 consecutive patients undergoing reconstruction after ablative surgery for head and neck carcinoma. Microvascular anastomoses were performed successfully using the exoscope in all patients, without any need for the conventional microscope. Arterial anastomoses were all end-to-end. Venous anastomoses were end-to-end in eight cases and end-to-side with the internal jugular vein in two cases. This study demonstrates the technical feasibility of microvascular anastomosis using a 4K three-dimensional exoscope system (VITOM 3D) in a series of 10 cases.

Refractory thyrotoxicosis induced by iodinated contrast agents treated with therapeutic plasma exchange. A case report.

Excess free iodide in the blood (ingested or injected) may cause thyrotoxicosis in patients at risk. Iodinated contrast solutions contain small amounts of free iodide and may be of significance for patients affected by Graves' disease, multinodular goiter or living in areas of iodine deficiency. Herein, we report a 57 elderly woman with a clinical history of multinodular goiter presented with a thyrotoxicosis induced by an iodinate contrast agent used during computed tomography scan. Because of the patient's resistance to conventional antithyroid drugs, she was treated with therapeutic plasma exchange (TPE). TPE is used in the treatment of several immunologic and nonimmunologic disorders. Temporary improvement after TPE in cases with thyrotoxicosis has been reported. In our patient's case, we observed an improvement in the thyroid hormone laboratory values as well as clinical findings. TPE can be an addition treatment when standard therapies for thyrotoxicosis fail providing the clinician with an adjuvant tool for rapid preparation of such a patient for thyroidectomy surgery.

Electrochemotherapy: a well-accepted palliative treatment by patients with head and neck tumours.

SUMMARY: Electrochemotherapy (ECT) is a well established treatment strategy for skin tumuors. The aim of this study was to evaluate the feasibility and efficacy of electrochemotherapy in the palliative setting in patients with head and neck malignancies, in terms of improvement of quality of life and in control of pain and bleeding. Twenty-four patients with a loco-regional M0/M1 relapse not suitable for cure with radical intent by surgery or radiotherapy (RT) and not suitable for systemic therapy and/or already treated with it, were admitted to ECT protocol treatment. Clinical features, treatment response, and adverse effects were evaluated. An overall response of 100% was observed. Overall survival probability at 24 months was 46.5% (median OS: 9 months). The multiple application of ECT was associated with improved survival (p = 0.02). Pain, need for medical assistance or dressing and bleeding events was significantly reduced at 1 month after ECT (p #x003C; 0.001). ECT is effective as palliative treatment of non-resectable head and neck malignancies. Its main advantages are improved quality of life, local tumour control and limited side effects.

Oral cavity and base of the tongue tumors. Correlation between clinical, MRI and pathological staging of primary tumor.

The diagnosis of oral cavity and oropharyngeal tumors can be obtained through clinical examination and biopsy. CT and MRI can then be used to define the extension of the disease. The aim of this study was to define the accuracy of clinical and MRI T staging of oral cavity and base of the tongue tumors and correlate the results with pathological data. Mandibular involvement, in a subgroup of patients, was determined and sensitivity, specificity, accuracy and positive and negative predictive values were evaluated. Fifty-nine patients affected by squamous cell carcinoma and 1 case of adenoido-cystic carcinoma were examined by means of a superconductive MR unit, using SE T1, and fat-suppressed T2 weighted sequences before contrast medium infusion. SE T1 and T1 fat-suppressed sequences after gadolinium-DTPA infusion were used. T stage accuracy of both clinical examination and MRI were found to be respectively 62% (k 0.459) and 82% (k 0.775). The sensitivity, specificity and accuracy of MRI in the detection of mandibular involvement were 94.1%, 60% and 81.5%, while the positive and negative predictive values were 80% and 85.7%, respectively. The sensitivity, specificity and accuracy of clinical examination in the detection of mandibular involvement were 100%, 30% and 74.1%, while the positive and negative predictive values were 70.8% and 100%. In the present study, MRI was seen to be an adequate technique for the assessment of oral cavity malignancies, in the evaluation of depth invasion, presence and extension of mandibular involvement.

Tracheotomy-related posterior tracheal wall rupture, trans-tracheal repair.

Laceration of the membranous part of the tracheo-bronchial tree is a rare complication that can occur after single lumen intubation, double-lumen intubation, percutaneous and surgical tracheotomy. The case of a 76-year-old male is presented in whom a posterior tracheal wall laceration, related to tracheotomy, was diagnosed and immediately treated at the end of a head and neck operation. A 6 cm long laceration started 1.5 cm below the tracheotomy level and ended 2 cm above the carina. The tear was closed from distal to proximal area via the tracheotomy opening with PDS 4/0 interrupted sutures using a thoracoscopic needle-holder. This original surgical technique is described in detail. In tracheotomy related tears, the fact that an opening in the trachea already exists and that the lesion rarely extends beyond the carina, should guide the surgeon to make every effort to repair the laceration through this already existing access.

Treatment of advanced neck metastases.

Despite the use of aggressive single or multimodality treatment protocols, patients with advanced cervical metastases, N2 and N3, have a poor prognosis because of their high risk of regional and distal failure. Moreover, N3 class does not allow resectability and curability to be defined. Numerous trials have been carried out in order to improve the oncological outcomes of patients with advanced metastases to the neck using a variety of multimodality therapy. At present, there is a trend toward the use of a definitive radiochemotherapy followed, or not, by neck dissection. In order to offer a panoramic view of the treatment protocols in use, data available in the literature, regarding the management of advanced neck disease using surgery, radiotherapy and chemotherapy, in different associations, have been reviewed and our experience reported. The presence of advanced cervical metastases is a very poor prognostic factor. The combined treatment modality offers better chances of cure than single modality treatment. Surgery followed by radiotherapy or chemo-radiation therapy is an effective and well standardized approach. The use of planned neck dissection following chemoradiation is still debated.

External monitor for buried free flaps in head and neck reconstructions.

Head and neck defects following oncological surgery must often be repaired with soft tissue and/or bone from other areas of the body. Significant loss of soft tissue requires flaps of sufficient bulk to adequately reconstruct the defect. Microvascular free tissue transfer is a good method for reconstructing even large defects following oncological surgery for head and neck cancer. Continuous post-operative monitoring of the perfusion of a free flap is vitally important to achieve not only a favourable outcome but also to decrease morbidity. Microvascular thrombosis occurs in 4% of the flaps and the best chance for flap salvage is offered by the earliest possible revision of the microanastomosis. Use of buried flaps in head and neck reconstruction makes monitoring particularly difficult and exteriorization of a segment of the flap permits a direct visualization. An original technique is presented for harvesting forearm free flaps with a secondary monitor skin paddle to externally check the status of the paddle and, when modified, can also be used for fibula and rectus abdominis flap.

Intraoperative radiation therapy as adjuvant treatment in locally advanced stage tumours involving the middle ear: a hypothesis-generating retrospective study.

The objective of this study was to evaluate the safety, effectiveness and functional outcomes of intraoperative radiotherapy (IORT) followed by intensity-modulated radiation therapy (IMRT) in locally advanced stage tumours involving the middle ear. Data on 13 consecutive patients treated for malignant tumor of external auditory canal involving the middle ear were retrospectively reviewed. Median follow-up was 33 months (range 6-133). Five (38%) patients were stage III and 8 (62%) were Stage IV according to the University of Pittsburgh staging system. Lateral temporal bone resection (LTBR) was performed in all cases. LTBR was associated with parotidectomy in 5 (38%) cases, and with neck dissection and parotidectomy in 6 (46%) cases. No patients had gross residual tumour. Surgical treatment was followed by IORT (12 Gy) and IMRT (50 Gy). Adjuvant chemotherapy was used in 4 (30%) cases. Preoperative and postoperative audiometric tests were performed to assess hearing loss. 5-year local-control (LC), 5-year distant-metastasis (DM), 5-year disease-free-survival (DFS) and 5-year overall-survival (OS) were calculated with Kaplan-Meyer method. Significant changes in bone conduction were reported after treatment. Partial flap necrosis was the only early complication observed in three (23%) cases, while meningeal fistula was seen in one (7.6%) case as a late complication. The 5-year LC-rate was 68%. The 5-year DM-rate was 90%. The 5-year DFS-rate was 61%. The 5-year OS-rate was 69%. IORT followed by IMRT for the treatment of advanced external auditory canal and middle ear tumours seems to be safe. No intraoperative death was reported. IORT may reduce the postoperative irradiation of remnant tissue obtaining the same full dose on the tumour bed. No complications of the residual external ear were observed. Detriment of neurosensory hearing may be expected. Future studies are required to confirm the benefit of this procedure in the ear.

Vastus lateralis myofascial free flap in tongue reconstruction.

In the last decade, the antero-lateral thigh free flap (ALT) has become the most popular free flap for tongue reconstruction because of less donor site morbidity and better cosmetic outcomes. However, fascio-cutaneous ALT may be insufficient to reconstruct major tongue defects, while its muscular-cutaneous variant (using the vastus lateralis muscle) may be too bulky. The present study describes our preliminary experience of tongue reconstruction with vastus lateralis myofascial flap, which could potentially offer unique advantages in head and neck reconstruction including adequate bulk when needed, optimal functional results and obliteration of dead space thus preventing fistulas and infections with minimal morbidity.