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.

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.

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.

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.

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.

Italian cross-cultural adaptation and validation of three different scales for the evaluation of shoulder pain and dysfunction after neck dissection: University of California - Los Angeles (UCLA) Shoulder Scale, Shoulder Pain and Disability Index (SPADI) and Simple Shoulder Test (SST).

Shoulder syndrome after neck dissection is a well known entity, but its incidence and prognostic factors influencing recovery have not been clearly assessed due to the heterogeneity of possible evaluations. The University of California - Los Angeles (UCLA) Shoulder Scale, the Shoulder Pain and Disability Index (SPADI) and the Simple Shoulder Test (SST) are three English-language questionnaires commonly used to test shoulder impairment. An Italian version of these scales is not available. The aim of the present study was to translate, culturally adapt and validate an Italian version of UCLA Shoulder Scale, SPADI and SST. Translation and cross-cultural adaptation of the SPADI, the UCLA shoulder scale and the SST was performed according to the international guidelines. Sixty-six patients treated with neck dissection for head and neck cancer were called to draw up these scales. Forty patients completed the same questionnaires a second time one week after the first to test the reproducibility of the Italian versions. All the English-speaking Italian patients (n = 11) were asked to complete both the English and the Italian versions of the three questionnaires to validate the scales. No major problems regarding the content or the language were found during the translation of the 3 questionnaires. For all three scales, Cronbach's α was > 0.89. The Pearson correlation coefficient was r > 0.91. With respect to validity, there was a significant correlation between the Italian and the English versions of all three scales. This study shows that the Italian versions of UCLA Shoulder Scale, SPADI and SST are valid instruments for the evaluation of shoulder dysfunction after neck dissection in Italian patients.

Step-by-step mandibular reconstruction with free fibula flap modelling.

The functional and aesthetic outcomes after segmental mandibular resection are closely related to the technique used during mandibular reconstruction with bone graft. The fibula free flap approach allows the possibility of using bone with/without skin for restoring the defect. Here, we aimed to establish the preplating technique for oromandibular reconstruction in a step-by-step fashion, based on 41 patients. The surgical technique is expounded in 8-10 steps. Preplating, plate removal, resection, replating, template modelling, contouring and fixation of the fibula represent the key points of the procedure. In this report, we show that the preplating and template modelling method is easy, does not incur extra costs and can be successfully used for mandibular reconstruction with bone graft. Functional and aesthetic results confirm the feasibility and reproducibility of the technique.

Salvage surgery after radiation failure in squamous cell carcinoma of the larynx.

AIM AND BACKGROUND: To investigate patients treated with radiotherapy (RT) for laryngeal squamous cell carcinoma (SCC) in order to estimate the recurrence rate and treatment used as salvage surgery. The survival rate in the group of patients treated with salvage surgery was compared to that of patients who had chemotherapy rather than surgery or who refused any treatment. METHODS: From 1989 to 1999, 185 patients came to our institution for laryngeal SCC. All of them underwent RT as primary treatment. Only patients with a minimum of three years follow-up (n = 143) were included in the study group. RESULTS: The 143 cases included 22 loco-regional recurrences (15.3%) during the minimum three years of follow-up. Recurrence was observed in the larynx in eighteen cases (81.8%), in cervical nodes in one case (4.55%) and in both the larynx and cervical nodes in one case (4.55%). There was peristomal recurrence in two cases (9.1%). Recurrence was observed after an average of 16.3 months. Fourteen patients (63.6%) out of the twenty-two cases of recurrence underwent salvage surgery. Surgery was not performed on the remaining eight patients (36.4%). The global survival rate was 92.3% after three years and 66.6% after five years in the group of patients treated with surgery. The actuarial survival rate was 100% after three years and 83.3% after five years. The global and actuarial survival rate was 20% after three years and 0% after five years in the group of patients who received chemotherapy rather than surgery or who refused any kind of treatment. CONCLUSION: The RT seems to play an important role in the loco-regional control of laryngeal SCC (especially in glottic T1). Salvage surgery for recurrence results in a good survival rate.

Effects of gastroesophageal reflux disease in laryngeal carcinoma.

Gastroesophageal reflux disease is associated with various otolaryngological disorders. The aim of this retrospective study was to determine the role of gastroesophageal reflux disease in the development of laryngeal squamous cell carcinoma (SCC) in non-smoking and non-drinking patients. The study population consisted of 36 consecutive non-smoking and non-drinking patients with histologically confirmed SCC of the larynx. As a control, a group of 125 lifetime non-smoking and non-drinking cancer-free subjects were selected. Patients with laryngeal cancer had a higher prevalence of gastroesophageal reflux disease than the control subjects (P < 0.0001). Our results confirm the fact that gastroesophageal reflux disease in itself is associated with an increased risk of laryngeal cancer.

Gastroesophageal reflux as a possible co-promoting factor in the development of the squamous-cell carcinoma of the oral cavity, of the larynx and of the pharynx.

According to recent advances it is assumed that the gastroesophageal reflux (GER) is a possible co-promoting factor of the squamous-cell carcinoma development in the upper parts of the gastro-intestinal and respiratory systems, considering the higher frequency of lesions due to acid in the studied population interested by GER. The aim of this study is to investigate 274 patients with malignant neoplasm of the oral cavity, of the pharynx and of the larynx, by esophago-gastro-duodenoscopy (EGD) and to compare the incidence of GER in this group with a control group of healthy patients from their hospital. Acid exposure in the upper level of the esophagus often remains unknown using traditional pH-monitoring, especially if no pharyngeal probe is used. When necessary a good diagnostic test is EGD with mucosa biopsy; it allows to directly examine the lesion. We retrospectively studied the data of 274 patients suffering from a cancer of the upper aero-digestive tracts by EGD in order to diagnose lesions caused by GER. We compared non-smoking patients affected by GER and tumours a control group of healthy patients. Statistical analysis revealed a significant difference between the two groups using the z-Test (p = 0.0001). In our study, based on endoscopic data, we observed a high percentage of non-smoking patients affected by GER and squamous-cell carcinoma of the upper parts of the airways and the gastrointestinal system. For this reason we consider GER as a possible co-promoting factor of cancer in some patients.

[Recurrent benign tumors of parotid gland: the role of the surgery]. / Ruolo della chirurgia nelle recidive dei tumori benigni della parotide.

Parotid gland tumor recurrences can prove problematic both in terms of facial nerve trauma during surgery and for the possible transformation into malignancy. Between 1981 and 2001 a total of 40 patients (23 women, 17 men; average age 48; age range 20-79 years) underwent surgery for recurrent parotid gland tumors. The average time between the first and the second surgical procedures was approximately 10 years. Five subjects underwent surgery several times for the same pathology. The Authors feel that MRI imaging is an essential tool for the evaluation of infiltrations into the soft tissues. The following surgical procedures were performed: enucleation in 2 cases; exofacial partial parotidectomy (PP) in 1; lower polar PP with functional neck dissection in 1; total parotidectomy (TP) with preservation of the facial nerve in 31 cases; TP with functional neck dissection in 2; TP with sectioning of the facial nerve in 2 and TP with transmandibular buccopharyngectomy and myocutaneous gran dorsal muscle flap in 1 case. Histology proved positive for the following: pleomorphous adenoma in 21 cases, adenocarcinoma in 11, aggressive fibromatosis in 2, cystadenolymphoma in 1, parotiditis in 1, lipoma in 1, cystic lymphoid hyperplasia in 1, histiofibrosarcoma in 1 and neurofibrosarcoma in 1. The surgical technique used was retrograde dissection of the facial nerve starting from one of the peripheral branches. Post-operatively, whenever a facial paralysis was encountered it proved difficult to recover. Paralysis of the nerve was permanent only in the 2 subjects where sectioning proved necessary because of infiltration by carcinoma. In 6 subjects recovery of the paralysis took one year, in 4 it took 6 months and in 2 other cases 3 months. In 22 cases there was only a slight paralysis of some branches which recovered during the post-operative period. We do not have definitive data on 4 subjects either because the period of time since surgery is still too short or because they did not come in for subsequent check-ups. The results of our study show that total parotidectomy should be the treatment of choice in case of benign parotid gland tumors and in particular for pleomorphic adenoma.