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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Electroporation Enhances Bleomycin Efficacy in Cats with Periocular Carcinoma and Advanced Squamous Cell Carcinoma of the Head.

BACKGROUND: Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival. OBJECTIVES: Evaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head. ANIMALS: Twenty-one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head. METHODS: Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2-8) were performed every other week until complete remission (CR) or tumor progression occurred. RESULTS: Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively. CONCLUSIONS: Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco-regional strategies for cancer therapy in sensitive body regions such as periocular region.

Ectopic lingual goiter treated by transoral robotic surgery.

Multinodular goiter in lingual thyroid is quite rare. Surgical removal is indicated in symptomatic patients and when cancer is suspected. An external approach is most often used, but is associated with morbidity and sequelae. In this study, we present for the first time the technique of transoral robotic surgery (TORS) for removal of a massive lingual goiter. Prospective patient data were collected, including demographics, medical history, symptoms, comorbidities and drugs prescribed. The da Vinci Surgical System was used for a transoral approach to the oropharynx. The technique was validated in a 31-year-old woman with signs and symptoms of multinodular goiter presenting since childhood. The procedure required 115 min, with intervals as follows: tracheotomy, 25 min; robot setting time, 20 min; and console time, 70 min. TOR S is feasible in cases of multinodular goiter in a lingual thyroid. The procedure appears to be safe, with quick recovery of swallowing and speech.

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.

Transoral robotic surgery (TORS) for tongue base tumours.

In recent years, transoral robotic surgery (TORS) has been used for the removal of pharyngeal and laryngeal cancers with the objective to improve functional and aesthetic outcomes without worsening the survival. This prospective single-centre cohort study described TORS in selected tumours of the tongue base in order to assess safety, efficacy and functional outcome of the procedure. From October 2010 to February 2012, TORS was performed in 13 consecutive patients affected by T1-T2 tumours of the base of the tongue. This procedure was applicable in all cases. The clinical stage demonstrated 8 T1 tumours and 5 T2 tumours. Neck node metastases were clinically evident in 6 cases (7 N0, 1 N1, 4 N2b and 1 N2c). The final pathology report confirmed malignancy in all cases (11 squamous cell carcinoma and 2 mucoepidermoid carcinoma). Negative-margin resections were obtained in all cases but one with close margins. Synchronous lymph node neck dissections were performed in 7 cases (6 monolateral, 1 bilateral). Patients underwent temporary tracheostomies for a mean time of 6 days. A naso-gastric feeding tube was positioned in 10/13 (76.9%) patients for a mean time of 7.5 days. The average time to carry out the TORS procedure was 95 min (set-up time 25 min; TORS 70 min). No deaths occurred. Surgical complications were observed in 4 cases (postoperative bleedings in 3 cases and intraoperative anaphylactic shock in 1 case). Median hospital stay was 9 days. All patients had good functional outcomes. Adjuvant treatment was indicated in 5/13 cases (35.4%). TORS represents a good tool for staging and treating neoplasm of the base of the tongue. The transoral removal is safe and can radically remove limited oropharyngeal tumours of the tongue base with good functional outcomes. The operating costs can be relatively high but they are related to the number of procedures per year, although the advantages to patients seem to justify the procedure. TORS can represent the definitive treatment in selected T1-T2 cases of base of the tongue tumours without adverse features and allow the possibility for the deintensification of adjuvant treatments.

Predictive factors for postoperative wound complications after neck dissection.

The objective of this retrospective study was to evaluate risk factors for wound complications after neck dissection. One hundred and nineteen patients were treated with neck dissection for squamous-cell carcinoma of the upper aerodigestive tract at the National Cancer Institute in Rome between 2006 and 2009. Postoperative wound complications were divided into major or minor and were related to different variables to identify risk factors. Postoperative wound complications were found in 20.2% of patients with an individual patient probability for different risk factors ranging from 2% to 34.1%. Preoperative chemoradiation therapy (CRT) and the type of neck dissection were associated with a higher risk of major complications (p ≤ 0.05). Previous CRT and radical neck dissection/modified radical neck dissection are risk factors for major wound complications in patients with head and neck squamous cell carcinoma undergoing neck dissection. Patients requiring neck dissection after CRT should be informed about the increased risk of the procedure, and selective neck dissection, if oncologically appropriate, should be considered to reduce complications.