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.

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.

Endoscopic endonasal management of non-functioning pituitary adenomas with cavernous sinus invasion: a 10- year experience.

BACKGROUND: The management of Non-Functioning Pituitary Adenoma (NFPA) invading the cavernous sinus (CS) is currently a balancing act between the surgical decompression of neural structures, radiotherapy and a wait-and-see policy. METHODS: We undertook a retrospective review of 56 cases of NFPA with CS invasion treated through an endoscopic endonasal approach (EEA) between 2000 and 2010. The Knosp classification was adopted to describe CS involvement using information from preoperative MRI and intraoperative findings. Extent of resection and surgical outcomes were evaluated on the basis of postoperative contrast-enhanced MRI. Endocrinological improvement and visual outcomes were assessed according to the most recent consensus criteria. RESULTS: EEA was performed using direct para-septal, trans-ethmoidal-sphenoidal or trans-ethmoidal-pterygoidal-sphenoidal approach. Visual outcomes improved in 30 (81%) patients. Normalization or at least improvement of previous hypopituitarism was obtained in 55% of cases. A gross total resection was achieved in 30.3% of cases. The recurrence-free survival was 87.5%, with a mean follow-up of 61 months (range, 36-166 months). No major intraoperative or postoperative complications occurred. DISCUSSION: EEA is a minimally-invasive, safe and effective procedure for the management of NFPA invading the CS. The extent of CS involvement was the main factor limiting the degree of tumor resection. The EEA was able to resolve the mass effect, preserving or restoring visual function, and obtaining adequate long-term tumor control.

Endoscopic transnasal resection of anterior skull base malignancy with a novel 3D endoscope and neuronavigation.

The surgical treatment of sinonasal malignancies is in continuous evolution. In selected patients, endoscopic resection has become a sound alternative to traditional external approaches. Further improvements are necessary to enhance the possibilities of endoscopic transnasal resection of sinonasal malignancies. We present a case of intestinal-type adenocarcinoma of the left nasal fossa eroding the skull base that affected a 56-year-old male. The patient was surgically-treated by means of a four-hand binarial endoscopic transnasal resection using a 3D endoscopic system and neuronavigation. Surgery was completed in 5 hours without significant complications. Surgeons were able to recognize and manage anatomical structures, and to control bleeding easily thanks to the bimanual technique and 3D visualization. The new 3D scopes and the bimanual technique under the guidance of a navigation system represent an interesting solution that can overcome the traditional limits of the traditional set up currently used.

Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma.

BACKGROUND: The importance of angiogenesis in melanoma has been controversial and is not homogeneous. Mast cell density (MCD) is highly correlated with the extent of both normal and pathological angiogenesis, such as that in chronic inflammatory diseases and tumours. METHODS: We evaluated the prognostic significance of tumour microvascular density (MVD) and MCD in 25 advanced melanoma patients after resection and a 4-5-year follow up: 48% of the patients were alive and free of metastases (good prognostic subgroup); 16% had developed regional nodal metastases (intermediate prognostic subgroup); and 36% had died (poor prognostic subgroup). Tissues samples were investigated immunohistochemically to count microvessels and mast cells with an antifactor VIII and an antitryptase antibody, respectively. RESULTS: Immunohistological staining showed a higher number of microvessels and mast cells in melanoma lesions of poor prognosis as compared with intermediate prognosis and with good prognosis, respectively. CONCLUSIONS: These data agree with those showing a close relationship between MCD and angiogenesis during tumour progression and demonstrate, for the first time, a prognostic significance of MCD in human melanoma.

Bronchioloalveolar lung carcinomas: K-ras mutations are constant events in the mucinous subtype.

Bronchioloalveolar carcinoma (BAC) is a form of peripheral lung adenocarcinoma growing as a single layer of malignant cells along the walls of terminal airways. The existence of BAC as a separate clinico-pathological entity has been a matter of controversy, mainly because its histogenesis is uncertain and it is not easily distinguishable from conventional lung adenocarcinoma (CLA). Three subtypes of BAC have been described using histological and cytological criteria: mucinous, non-mucinous, and sclerosing. The clinical behaviour of BAC appears to be dependent on the histological subtype. The different morphological patterns and clinical outcome of the subtypes of BAC suggest that their biological behaviour may be different from one another and from CLA. This study has investigated 58 BACs (10 mucinous, 40 non-mucinous, and 8 sclerosing) and 50 control CLAs for mutations at codon 12 of the K-ras oncogene. Twenty-one (36 per cent) BACs and 13 (26 per cent) CLAs showed K-ras mutations. A clear association (P < 0.0001) between K-ras mutations and the mucinous type of BAC was observed: all 10 mucinous tumours examined were scored positive for mutations in the K-ras gene, while only 9 (23 per cent) of the 40 non-mucinous and 2 (25 per cent) of the 8 sclerosing BACs were found to be positive. The frequency of ras mutations in non-mucinous BAC, sclerosing BAC, and CLA was not statistically different. Our data indicate that BACs are a heterogeneous group of lung tumours and that the mucinous form might represent a biological entity separate from both the other two BAC types and CLA.

[Olfactory neuroblastoma. Presentation of a case]. / Il neuroblastoma olfattorio. Presentazione di un caso.

Olfactory neuroblastoma is an uncommon and hardly diagnosable neoplasm. The conventional histologic analysis allows generally a diagnosis of undifferentiated carcinoma. The immunohistochemical procedures, particularly the S-100 Protein and the Enolase Neuron-Specific, may contribute to define the diagnosis as well as in a patient recently observed by the authors.

Histopathological study of a case of systemic angiofollicular hyperplasia (Castleman's disease).

This report describes the nodal and hepatic lesions observed in a patient with generalized disorders that had been histologically diagnosed as a systemic angiofollicular hyperplasia. The diagnostic morphological findings were observed in the nodes of the axilla and were represented by diffuse marked plasmacytosis, prominence of the germinal centres, preservation of the architecture with a reactive proliferation of blood vessels and fibrous tissue in interfollicular areas.