Massimiliano Garzaro

Cell cycle and viral and immunologic profiles of head and neck squamous cell carcinoma as predictable variables of tumor progression

The aim of this study was to determine whether the aberrant expression of cell‐cycle or immune‐response markers together with human papillomavirus (HPV) positivity impacts patient survival in different head and neck squamous cell carcinoma (HNSCC) subsets.

Radiofrequency Inferior Turbinate Reduction Long-Term Olfactory and Functional Outcomes

Objective. The aim of this study was to assess the long-term effects of radiofrequency inferior turbinate reduction (RITR) on nasal function in patients affected by nasal obstruction secondary to turbinate hypertrophy, focusing attention on increased sense of smell and its persistence after a 2-year follow-up. Study Design. Case series with planned data collection. Setting. ENT division, university hospital. Subjects and Methods. A total of 40 consecutive patients undergoing RITR for allergic or nonallergic chronic rhinitis with inferior turbinate hypertrophy were included. We planned a series of tests, including the “Sniffin’ Sticks” test battery, anterior rhinomanometry, and the nasal Obstruction Symptom Evaluation (NOSE) scale, on the day of the procedure and at the 2-month and 2-year follow-up visits. Results. Of the 40 patients, 35 completed all the objective and subjective examinations on the day of the procedure and at the 2-month and 2-year follow-up visits. The authors found a significant decrease in nasal resistances from a mean of 1.13 Pa/cm3s−1 preoperatively to a mean of 0.29 Pa/cm3s−1 2 years postoperatively and improvement in odor threshold, discrimination, and identification scores 2 years postoperatively. The NOSE score diminished significantly 2 years after surgery from a mean of 23.14 to a mean of 4.14 (all P < .01 with the t test for repeated measures). Conclusion. This long-term evaluation showed that radiofrequency treatment for allergic or nonallergic inferior turbinate hypertrophy appeared to provide improvement in olfaction, decrease nasal resistances, and have subjective benefits, maintained 2 years after the procedure.

Clinical and Biological Prognostic Factors in 179 Cases with Sinonasal Carcinoma Treated in the Italian Piedmont Region

Objectives: In spite of aggressive surgery and high-dose radiotherapy, the long-term survival of patients with sinonasal cancer remains disappointing. In this paper, we report data from 179 consecutive cases treated in the Italian Piedmont region between 1996 and 2000 according to a fixed protocol. Methods: Clinical and pathological data and the following biological parameters were analyzed: microvessel density and growth fraction by CD31 and Ki-67 positivity, respectively, and immunohistochemical expression of vascular endothelial growth factor (VEGF). Results: The median follow-up period was 75 months (range 45–108 months). Median overall survival was 26 months; 2- and 5-year overall survival rates were 52 and 36%, respectively. Patients with T1-T2 adenocarcinoma and squamous cell cancers (SCC) had better median survival than those with other lesions (p < 0.05). Patients treated with surgery with or without radiotherapy had better survival (p < 0.01), while chemotherapy had a marginally favorable effect (p = 0.09). The type of surgery and radiotherapy dose had no impact on survival; in contrast, there was a strong association between Ki-67 expression and microvessel density and overall survival (p < 0.05 and p = 0.039, respectively), while VEGF-C was a prognostic factor in SCC patients only (p < 0.05). Conclusions: In sinonasal cancer, tumor stage and histology have a clear impact on survival; surgery with or without radiotherapy represents the main choice of treatment for such tumors. The efficacy of neoadjuvant and concomitant chemoradiotherapy needs to be further investigated. The proliferative index and angiogenesis show a major role in the natural history of this cancer.

Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population

BACKGROUND AND PURPOSE Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC. MATERIALS AND METHODS Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m(2)) plus epirubicin (90 mg/m(2)), followed by cisplatin (100 mg/m(2)) and concomitant radiotherapy (70 Gy). RESULTS In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%. Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%. CONCLUSIONS NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.

Radiofrequency volume turbinate reduction versus partial turbinectomy: clinical and histological features.

Background Nasal obstruction is a common symptom related to turbinate hypertrophy in 20% of cases. When medical treatment failed different surgical options were available. Actually, nasal physiology impairment after surgical treatment is not fully clear. This study evaluates microscopic mucosal changes and physiological function, by means of mucociliary transport time (MCT), after radiofrequency volume turbinate reduction and partial inferior turbinectomy. Methods Forty-eight nonallergic patients were treated for chronic nasal obstruction. Twenty-six patients (group A) underwent radiofrequency turbinate reduction and 22 patients (group B) underwent partial turbinectomy associated with septoplasty. Mucosal specimen obtained before T0 and 6 months (T1) after surgery were compared by means of optical microscope and transmission electron microscope. All patients were evaluated using MCT at T0 and T1. Results Optical analysis showed circumscribed squamous metaplasia and fibrosis in specimens obtained from group A. Same changes were more evident in group B. Ultrastructural analysis evidenced loss of ciliated epithelium in group B, whereas in group A a normal number of cilia was found. In all patients at T1, MCT time was prolonged in comparison with the preoperative values. After surgery, group B showed significantly prolonged MCT in comparison with group A (p < 0.05). Conclusion In our study both surgical techniques achieved good clinical outcomes with improved nasal function, although the ciliated epithelium appeared partially impaired. These findings resulted in a prolonged MCT in all patients, especially those treated with partial turbinectomy. Compared to partial resection, intraturbinal turbinate reduction seems to be the method of choice to better preserve nasal physiology.

Functional and psychological evaluation after flap reconstruction plus radiotherapy in oral cancer.

Head and neck tumors and their treatments negatively affect speech, swallowing, body image, and quality of life (QOL). The purpose of this study was to allow us to evaluate the impact of flap reconstructive surgery with adjuvant radiotherapy (RT) on QOL and psychological functioning.

Radiofrequency inferior turbinate reduction: An evaluation of olfactory and respiratory function

OBJECTIVE: The aim of this study was to assess the outcomes after radiofrequency inferior turbinate reduction (RITR) on objective and subjective nasal function in patients with nasal obstruction caused by turbinate hypertrophy and to evaluate the possible effect on olfactory function. STUDY DESIGN: Case series with planned data collection. SETTING: ENT division, university hospital. SUBJECTS AND METHODS: Forty consecutive patients who underwent RITR for allergic or nonallergic chronic rhinitis with inferior turbinate hypertrophy were tested before and two months after the surgical procedure, using the Sniffin’ Sticks test battery, anterior rhinomanometry, and the nasal obstruction symptom evaluation (NOSE) scale. RESULTS: The total basal nasal resistance at 150 Pa diminished significantly two months after surgery. Preoperative olfactory tests showed anosmia in five percent (n = 2) of the patients, hyposmia in 82 percent (n = 33), and normosmia in 12 percent (n = 5). At two months from the intervention, two percent (n = 1) were diagnosed as anosmic, 12 percent (n = 5) as hyposmic, and 85 percent (n = 34) as normosmic. The means of preoperative odor threshold (T), discrimination (D), identification (I), and the overall TDI score improved significantly postoperatively (P > 0.001). The NOSE score in the two-month follow-up improved in 97.5 percent (n = 39) of patients, with a mean difference in pre- vs. postintervention score of 40.12 (95% confidence interval 35.75-44.25; P < 0.001). CONCLUSION: RITR may provide excellent outcomes in terms of improvement in olfactory function and nasal flow in patients affected by turbinate hypertrophy refractory to medical therapy.

The Expression of TSLP Receptor in Chronic Rhinosinusitis with and without Nasal Polyps

Chronic Rhinosinusitis with or without Nasal Polyps (CRSwNP and CRSsNP) may be characterized by different cytokine profiles. Generally, Th2 cytokines and eosinophilic infiltration have been reported to be more specific of CRSwNP compared to CRSsNP, where neutrophils seem to play a major role. The epithelial cell-derived thymic stromal lymphopoietin (TSLP) has been recently identified as a key factor in Th2-inflammatory response. The aim of this study is to investigate the expression of TSLP Receptor (TSLP R) in surgical specimens obtained from patients affected by CRSwNP (n=10) and CRSsNP (n = 5) by immunohistochemical techniques (immunostaining score, IS). TSLP R expression was significantly higher in the inflammatory infiltrate and in the epithelial cells of CRSwNP, CRSsNP patients compared to the control group (IS 4.5±0.68, 4.4+1.44 and 0.4310.3 respectively, p=0.0024 for inflammatory infiltrate and IS 5.8±0.92, 7.8±2.06 and 0.86±0.55 respectively, p=0.0018 for epithelial cells). No significant difference was observed in IS of inflammatory infiltrate and epithelial cells in CRSwNP compared to CRSsNP. Very low IS for TSLP R was found in connective tissue of all the samples, with no difference among the groups. TSLP receptor is highly expressed in CRS compared to controls and independently from the polyps suggesting an early common inflammatory pathway in the two CRS phenotypes.

Stage III-IV sinonasal and nasal cavity carcinoma treated with three-dimensional conformal radiotherapy

AIMS AND BACKGROUND To report the dosimetric data and clinical outcomes of patients with advanced neoplasm of the paranasal sinuses and nasal cavity, treated by three-dimensional conformal radiotherapy. METHODS Between 2000 and 2005, 31 consecutive patients were treated for locally advanced tumors of paranasal sinuses and nasal cavity. The primary tumor was located as follows: maxillary sinus 15 (48.4%); ethmoid sinus 10 (32.3%); nasal cavity 6 (19.3%). The patients were separated in two groups according to the modality of treatment: group A included 21 patients treated with postoperative three-dimensional conformal radiotherapy with or without chemotherapy; group B included 10 patients treated with radical three-dimensional conformal radiotherapy with or without chemotherapy. The median radiation dose to the planning target volume was 60 Gy (range, 56-63) for patients who underwent complete surgical resection and 68 Gy (range, 64-70) for those who did not have tumor resection or patients with residual disease. RESULTS The median follow-up was 42 months. Five-year local tumor control and overall survival actuarial rates were 74% and 72%, respectively, in the postoperative setting, 20% and 25%, respectively, with the primary radiotherapy. Local recurrence was the most common site of failure. No patient developed radio-induced blindness; 4 patients underwent enucleation as part of radical surgery. Dosimetric data are reported. CONCLUSIONS The local control rate for these tumors remains low. The prognosis depends on localization, tumor stage and treatment modality. Three-dimensional conformal radiotherapy reduces the risk on optical pathways but does not modify outcome.

Eosinophilic inflammation of chronic rhinosinusitis with nasal polyps is related to OX40 ligand expression

The aims of this study were to investigate OX40 ligand expression in sinus tissue from patients with nasal polyposis compared with patients with chronic rhinosinusitis without nasal polyps (NPs), and to determine if OX40 ligand expression is related to eosinophilic sinus infiltration. Twenty patients with chronic rhinosinusitis (11 with and nine without NPs) and seven controls were enrolled in the study. The mRNA expression of OX40 ligand and thymic stromal lymphopoietin and its receptor were analyzed. The immunoreactivity score for OX40 ligand and the eosinophil count were obtained. The mRNA expression and immunoreactivity score of OX40 ligand were higher in patients with nasal polyposis than in patients without NPs, as well as healthy controls. The mRNA expression of thymic stromal lymphopoietin and its receptor was significantly higher in nasal polyposis than in the control, but not significantly higher than in chronic rhinosinusitis without NPs. A correlation between the number of OX40 ligand-positive cells and the number of eosinophils in sinus biopsies was found only in patients with nasal polyposis. In conclusion, the thymic stromal lymphopoietin/OX40 ligand axis is up-regulated in nasal polyposis and is related to the intensity of eosinophilic inflammation.