Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area.

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

Test-retest reliability of the VOR as measured via Vorteq in healthy subjects.

To determine the reliability of the vestibolo-ocular reflex test measured via Vorteq, 16 subjects underwent head-autorotation test at the frequencies 1-5 Hz. All patients underwent the re-test. No linear correlation was observed between the measurements, i.e., no repeatability of the same measurements at the various frequencies. The Head Auto-Rotation Test by Vorteq has demonstrated advantages: patients are not disturbed by the active head movements; the full test protocol, lasts only a few minutes; the method enables the vestibolo-ocular reflex to be evaluated at high head-rotation frequencies. However, the test has disadvantages: poor test-retest inter-individual repeatability, wide standard deviations of results with heterogeneous inter-individual spread with regard to phase and asymmetry values especially at high rotation frequencies. In the light of the above findings, it can be seen that the test-retest of the Vorteq system is not sufficiently reliable and hence cannot be used in clinical practice.

Usefulness of virtual endoscopic three-dimensional reconstructions of the middle ear.

This work uses a new programme for producing 3D radiological images acquired by means of CT which enables the internal surfaces of the examined structures to be visualized. This new method, which is able to navigate inside organs in a similar way to fibreoptic endoscopy, is known as virtual endoscopy. CT examinations of the temporal bone were carried out using spiral equipment and endoscopic 3D processing was carried out on a separate workstation equipped with a volume-rendering programme. Once the technical parameters necessary for obtaining a representation of the internal surfaces had been defined, a simulation of a virtual otoscopy was conducted by moving the virtual endoscope from the external auditory canal through the annulus to the tympanic cavity. The simulation can be obtained either by moving the endoscope by hand, using the mouse, or by defining a path along which the software automatically creates an endoscopic 3D reconstruction. The images thus obtained are projected sequentially to give a "movie" effect, i.e. a continuous progression of the endoscope. The average time required to conduct the procedure ranges from 20 to 30 min. A virtual endoscopic visualization of the middle ear was obtained which, in particular, generated images of the tympanic cavity with the ossicular chain. In our experience, virtual otoscopy shows the anatomy of the structures of the tympanic cavity in excellent detail and may be considered complementary to CT, providing useful images enabling better visual representation and understanding of this complex structure. Although clinical applications of the technique remain to be defined it may have a role to play in presurgical diagnostic evaluation of the ossicular chain, epitympanum and retrotympanum.

[Descending necrotizing mediastinitis. Clinical experience and review of the literature]. / La mediastiniti discendenti. Esperienza clinica e revisione della lettertaura.

The occurrence of a Descending Necrotizing Mediastinistis (DNM) usually is a consequence of oropharyngeal infections, which ultimately invade the mediastinum via the cervical fasciae. The clinical course is rapid and often fatal, and is associated with severe systemic symptoms, including fever and hypotension. In these cases, an aggressive surgical approach associated with an appropriate antibiotic treatment is mandatory. Personal experience in the treatment of DNM is presented and a review of the current literature is made; moreover an operative algorhythm is presented.

Surgical treatment of tracheostomal stenosis.

HYPOTHESIS: Stenosis of the tracheostome is a frequent complication following total laryngectomy; the problems created by tracheostomal stenosis are the result of reduced airflow and consequent turbulence. Many authors have studied etiological factors for the onset of stomal stenosis, and a number of procedures have been recommended for the surgical correction of such stenosis. STUDY DESIGN: A prospective analysis of 12 patients who underwent surgical correction of stomal stenosis is presented. METHODS: At the Institute of Clinical Otolaryngology we have recently defined a surgical technique for the correction of stomal stenosis that combines radial incisions, V-shaped flaps, and interposing flaps. This technique enables us to correct all the types of stenosis, and we have treated 12 patients to date. RESULTS: To date, the average follow-up has been 17 months (range, 3-36 mo), and the results are encouraging. Early stenosis of the tracheostoma reappeared in one patient, who had successful repeat surgery with the same technique. CONCLUSIONS: Early results suggest the routine use of this surgical technique in the treatment of stomal stenosis.

Benign positional vertigo without detectable nystagmus.

OBJECTIVES: To demonstrate that for treatment of benign positional vertigo it is not necessary to identify a positional nystagmus. STUDY DESIGN: Prospective trial of 43 patients with positional vertigo without clinical evidence of positional nystagmus who were treated with a modified canal-repositioning maneuver. METHODS: Results were compared with the results obtained in the treatment of posterior semicircular cupolo-canalithiasis with typical positional nystagmus with the same repositioning maneuver. RESULTS: Treatment of 43 patients with positional vertigo without positional nystagmus resulted in a 60.46% (26/43) complete recovery rate and a 6% (3/43) persistence of disorder rate compared with a 90% complete recovery rate obtained in 90 patients with typical benign positional paroxysmal vertigo (with positional nystagmus). CONCLUSIONS: What is attempted by this work is to confirm that through clinical evaluation based on history and positioning tests alone, one can obtain acceptable results in treatment of supposed canalithiasis without having detected the pathognomonic nystagmus.

External osteotomy in rhinoplasty.

OBJECTIVES: To compare external and internal lateral osteotomy in rhinoplasty. STUDY DESIGN: Retrospective review and study on cadavers. METHODS: One hundred forty-two patients who underwent aesthetic rhinoplasty were examined. The following criteria were taken into consideration: edema and ecchymosis around the eyes, the degree of closure of the roof, symmetry and level of fractures, solidity of the bone pyramid, and any scarring at the access point of the osteotome. In the last 25 patients who had surgery, a nasal endoscopy with optical fibers was carried out to evaluate any damage to the mucosa caused by the 2-mm osteotome. Furthermore, to compare the two routes in vivo, for five of these patients a lateral osteotomy was carried out externally for one side and internally for the other. Lateral osteotomy were performed on five cadavers by an external route on one side and by an internal one on the other. A midface degloving procedure was performed to expose the osteotomy sites. RESULTS: Edema and ecchymosis were always much less severe in patients who were treated with external osteotomy. The control of the fracture line was always excellent. Endoscopic evaluation and study on cadavers revealed damages to the mucosa caused from the internal osteotomy and a better control of fracture line in external osteotomy. CONCLUSIONS: External osteotomy is an easy and precise approach. Because the fracture is of a greenstick type, the bone stumps are stable. The reduced bleeding reduces the formation of edemas and ecchymosis around the eyes. The damage to the nasal mucosa is minimal, and the cutaneous scars are virtually invisible a month after surgery.

[Bilobed flap in the reconstruction of cheek defects]. / Il lembo bilobato nella ricostruzione dei difetti della guancia.

The bilobed flap is a reliable means for the reconstruction of facial defects in one stage. This reconstruction technique has been applied on a 69-years-old man affected by carcinoma of the cheek, involving overhanging skin and underlying oral mucosa. Stensen's duct reconstruction was also performed with a vein graft and, 8 months later, deviation of the rima oris was corrected by inserting a goretex strip at the level of the upper lip elevator muscle. The present work considers the bilobed flap as a means for cheek defects reconstruction compared with other reconstruction techniques.

Modified particle repositioning procedure.

OBJECTIVES: To evaluate the efficacy of modifications to traditional particle repositioning maneuvers in the treatment of benign paroxysmal positional vertigo. STUDY DESIGN: Prospective trial of 118 patients with cupolocanalithiasis of the posterior canal treated with three different canal-repositioning techniques. METHODS: Results were compared with the maneuvers employed and the statistical importance of rotating patients by 360 degrees along their longitudinal axis and head shaking on reaching each single position were evaluated. RESULTS: Treatment of patients with our maneuver, which, in comparison with traditional repositioning maneuvers, was modified by breaking the procedure up into seven positions and rotating patients by 360 degrees along their longitudinal axis, gives a higher, but not statistically significant, number of treatment successes (84.5%) than the traditional Parnes maneuver (60%) (P = .154); treatment of a third group of patients with our modified particle repositioning maneuver with the addition of head-shaking on reaching each single position gives a higher (95.6%), statistically significant number of treatment successes than traditional Parnes maneuver (P = .00011). CONCLUSIONS: The success rates achieved from modified particle repositioning maneuvers are statistically significant. Onset or persistence of dizziness, which patients frequently complain of after liberatory maneuvers, affects only 5.6% of the patients treated. This low incidence is statistically correlated to head-shaking.

Predictive factors of nodal metastases in oral cavity and oropharynx carcinomas.

OBJECTIVE: To estimate the value of tumor (T)-related parameters (singly or in association) in predicting the presence of occult metastases in oral cavity and oropharynx carcinomas. STUDY DESIGN: We considered tumor size (T size), Broders' grading of histologic differentiation (G), invasive cell grading (ICG), and thickness. For every single factor, we evaluated the correlation between the parameter and occult metastases in N0 neck disease, the correlation between the parameter and metastases independently from node (N) class, and the relation between the parameter and extracapsular spread. On the basis of previous results, we gave a score to each parameter that showed higher significativity the sum of which we called global score (GS). We compared the predictivity of metastasis of the GS to that of the single parameters to obtain a more efficacious index. METHODS: Sixty-one patients with carcinomas of the oral cavity and oropharynx who underwent surgery on T and N were examined. RESULTS: Our preliminary results have highlighted a significant correlation between G, ICG, and the presence of occult metastases. No correlation between T size and metastases was highlighted. The GS obtained from G and ICG turned out to be highly significant. A strong correlation was found between the ICG score and extracapsular spread: a high risk of extracapsular spread was found in patients with an ICG score > or =13. CONCLUSION: We perform elective neck dissection in T1-T2 N0 neck disease with ICG > or =13 and GS1 > or =9.

Oncological and functional results by horizontal glottectomy in laryngeal carcinomas.

BACKGROUND: The aim of this study is to describe the indications, surgical technique and results of horizontal glottectomy in laryngeal carcinomas. MATERIALS AND METHODS: Twenty patients suffering from differentiated glottal carcinoma (15 T1b and 5 T1a) were treated between 1985 and 1994. A classic horizontal glottectomy, with some modifications, not extended to the ventricular fold or to the arytenoid, was performed in every patient. All patients followed a postoperative rehabilitative program. Time of feeding tube removal, decannulation and voice production were considered. RESULTS: No local recurrence was recorded in any of the patients, however follow up on 4 cases was only three years. No postoperative radiotherapy was used. Two patients died from cardiovascular causes. Post-operative average times were: discharge from hospital after 10.5 days; feeding tube removal after 7 days; decannulation after 9.5 days. No major pulmonary complications nor laryngeal stenosis following surgery was recorded. In all patients adequate voice production was achieved. CONCLUSIONS: Our results show that horizontal glottectomy is a safe procedure in the treatment of laryngeal cancer. Local control of disease, provided case selection is very accurate, can reach 100%. Rapid and excellent laryngeal function may thus be obtained and the voice production is adequate in every patient.

Pre-operative evaluation of cervical adenopathies in tumours of the upper aerodigestive tract.

BACKGROUND: Carcinomas of the upper aerodigestive tract are characterized by a high incidence of local metastasis in the neck. The presence of lymph node metastasis represents the most unfavorable prognostic factor for these tumors. A diagnostic routine is needed in order to identify the highest number of neck metastasis, thereby optimizing the selection of patients eligible for surgical neck treatment and reduce costs and length of hospital stay. MATERIALS AND METHODS: Our study analyzes the sensibility, specificity, and diagnostic accuracy of clinical examination, echography (US), computed tomography (CT) in cervical metastasis detection by comparing them with the histopathological examination of the neck dissection specimens (pN) in 53 patients suffering from carcinoma of the upper aerodigestive tract. RESULTS: Clinical examination: sensibility 82.1%; specificity 80%; diagnostic accuracy 81.1%; US with a cut off point for minimal adenopathy diameter of 0.5 cm 92.8% sensibility, 60% specificity, 77.3% diagnostic accuracy; US with cut off point 1 cm 82.1% sensibility, 80% specificity, 81.1% diagnostic accuracy; US with cut off point 1 cm, also considering round shape or multiplicity of the adenopathy: 82.1 sensibility, 80% specificity, 81.1% diagnostic accuracy; CT with cut off point 0.5 cm: 92.8% sensibility, 32% specificity, 64.1% diagnostic accuracy; CT with cut off point 1 cm: 85.7% sensibility, 64% specificity, 75.4% diagnostic accuracy; CT with cut off point 1 cm, also considering central necrosis, extracapsular spread, multiplicity of the adenopathy 89.2 sensibility, 60% specificity, 75.5% diagnostic accuracy. CONCLUSIONS: By relating the results obtained from preoperative methods to the anatomopathological analysis of the surgical specimens we can draw the following conclusions: a) a neck positive to palpation in a subject with carcinoma of the upper aero digestive tract must be submitted to neck dissection. Such patients have an 81.1% likelihood of having a metastasis. In these patients the use of radiologic studies of the neck must be restricted to cases with uncertain involvement of retropharingeal, mediastinic, paratracheal lymph nodes or in the follow-up after treatment; b) a neck negative to palpation in a subject with carcinoma of the upper aero digestive tract, must be further investigated. The US and the CT must use a cut-off point of 1 cm to consider a neck positive. Radiologic criteria for malignancy, i.e., multiplicity, roundish shape, central necrosis and capsular invasion do not significantly increase the diagnostic accuracy of the radiographic methods; c) the combined use of US and CT does not offer significant advantages in the detection of metastasis, in any case CT is preferable when primary tumor has to be evaluated; d) the assessment of patients that are negative to palpation and to US and to CT must consider the parameters linked with primary tumor, such as site and size, Broder's grading, Invasive Cell Grading, and thickness.