Cholesteatoma vs granulation tissue: a differential diagnosis by DWI-MRI apparent diffusion coefficient.

PURPOSE: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. METHODS: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. RESULTS: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10- 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10- 3 mm2/s) group (p < 2.2 × 10- 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10- 3 mm2/s. CONCLUSIONS: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.

Facial pain: sinus or not?

Facial pain remains a diagnostic and therapeutic challenge for both clinicians and patients. In clinical practice, patients suffering from facial pain generally undergo multiple repeated consultations with different specialists and receive various treatments, including surgery. Many patients, as well as their primary care physicians, mistakenly attribute their pain as being due to rhinosinusitis when this is not the case. It is important to exclude non-sinus-related causes of facial pain before considering sinus surgery to avoid inappropriate treatment. Unfortunately, a significant proportion of patients have persistent facial pain after endoscopic sinus surgery (ESS) due to erroneous considerations on aetiology of facial pain by physicians. It should be taken into account that neurological and sinus diseases may share overlapping symptoms, but they frequently co-exist as comorbidities. The aim of this review was to clarify the diagnostic criteria of facial pain in order to improve discrimination between sinogenic and non-sinogenic facial pain and provide some clinical and diagnostic criteria that may help clinicians in addressing differential diagnosis.

Septoplasty: is it possible to identify potential "predictors" of surgical success?

Septoplasty is one of the most frequent surgical procedures performed by otolaryngologists. Despite successful surgical correction, many patients are not satisfied with their outcomes. So far, in clinical practice there is no consensus of opinion about the reliability of objective measurements of nasal patency and the correlation between objective measurements and subjective nasal patency symptoms. This study aims to assess the reasons for patient dissatisfaction after septoplasty and optimise pre-operative diagnostic management to predict surgical outcomes. We analysed 494 patients undergoing septoplasties with turbinoplasty by subjective Nasal Obstruction Symptom Evaluation questionnaire (NOSE) and objective active anterior rhinomanometric measurements before surgery and after 6 months. In our series, 17% had postoperative septal re-displacement; all patients had an anterior deviations at baseline. We found that the type of septal deviation, anterior vs posterior, was a significant predictor of postoperative functional improvement, whereas demographic characteristics as age, gender and smoke habit were not. Our data suggest that the anterior segment of the nasal septum was the most critical area for nasal airway resistance and more difficult to manage because it is likely to re-displace vs the posterior one and for this reason it represents a negative predictor of postoperative satisfaction.

Cyberknife® system: a new therapeutic strategy for sinonasal solitary extramedullary plasmacytomae.

Sino-nasal solitary extramedullary plasmacytoma (EMP) is a rare neoplasm with unpredictable progression to multiple myeloma. To improve the precision of irradiation delivery, preserving the healthy surrounding tissue and critical structures we used a CyberKnife® for the treatment of sinonasal solitary extramedullary plasmacytoma. We present the first case of sinonasal-EMP treated with CyberKnife®-stereotactic radiotherapy (SRT) with a complete remission without adverse events. Based on the post-therapeutic results and healthy tissue preservation, we believe that CyberKnife®-SRT represents a good therapeutic option for the treatment of sinonasal-EMP.

Mathematical model for preoperative identification of obstructed nasal subsites.

The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up.

An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicentre studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity < 10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%.

Ancillary therapy of intranasal T-LysYal® for patients with allergic, non-allergic, and mixed rhinitis.

Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction. Non-allergic rhinitis (NAR) is characterized by a non-IgE-mediated pathogenesis. Frequently, patients have the two disorders associated: such as mixed rhinitis (MR). Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert anti-inflammatory and immune-modulating activities. Recently, an intranasal HA formulation was proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (rinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 89 patients (48 males and 41 females, mean age 36.3±7.1 years) with AR, NAR, and MR. Patients were treated with intranasal T-LysYal® or isotonic saline solution as adjunctive therapy to nasal corticosteroid and oral antihistamine for 4 weeks. Patients were visited at baseline, after treatment and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells. In conclusion, the present study demonstrates that intranasal T-LysYal® is able, as ancillary therapy, to significantly improve patients with AR, NAR, and MR, and its effect is long lasting.

Intranasal T-LysYal® as adjunctive therapy for patients after functional endoscopic sinus surgery.

Functional Endoscopic Sinus Surgery (FESS) is a common day surgery technique for upper airway disorders. Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert reparative, anti-inflammatory and immune-modulating activities. Recently, a new intranasal HA formulation has been proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (RinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 83 patients (49 males and 34 females mean age 45.4±6.2 years) treated with FESS. All patients were treated with isotonic saline solution for 4 weeks, and a sub-group (active group) was also treated with intranasal T-LysYal®. Patients were visited at baseline, after treatment, and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells in comparison to isotonic solution. In conclusion, the present study demonstrates that intranasal T-LysYal® is able to significantly improve patients after FESS and its effect is long lasting.

Sodium hyaluronate improves quality of life and nasal endoscopy features in preschool children with upper respiratory tract infections.

The aim of this prospective, randomised study was to evaluate the effects of nasal douches with sodium hyaluronate on clinical and endoscopic variables, on parental perception of their child’s health-related quality of life (HR-QoL), and on parental workdays lost in preschool recurrent upper respiratory tract infections (URTIs). Children aged 2-6 years with recurrent or persistent URTIs underwent at baseline the evaluation of upper respiratory tract symptoms in the previous two weeks, and nasal endoscopy. Parents of enrolled children were assessed for self-perception of their children’s HR-QoL using a standardised questionnaire. The same variables were reassessed after a 2-week treatment with either 9 mg sodium hyaluronate plus saline solution or saline alone by nasal douches. Forty of the 48 children enrolled completed the study (22 assigned to the combined treatment). Compared to baseline, the combined treatment resulted in a significant reduction of the prevalence of children with missed daycare days (45% vs 14%, p=0.04) and of parents with workdays lost (36% vs 5%, p=0.02), and in a significant improvement of HR-QoL score (3.7 vs 2.8, p=0.004). At endoscopy, the secretion and mucosal oedema score significantly improved after the combined treatment (6 vs 2, p < 0.001), and there was a trend towards a reduction of the adenoid hypertrophy score (p=0.06). No clinical, HR-QOL or endoscopy changes were found in the saline group. In preschool children with recurrent or persistent URTIs, sodium hyaluronate by nasal douche significantly improves endoscopic features. Additional benefits include the children’s HR-QoL and daycare attendance, and parental work.

Concha bullosa related headache disability.

OBJECTIVE: Rhinogenic headache (RH) is a headache or facial pain syndrome secondary to mucosal contact points in the sino-nasal cavities, in the absence of inflammatory signs, hyperplastic mucosa, purulent discharge, sino-nasal polyps or masses. It may result from pressure on the nasal mucosa due to anatomical variations among which the pneumatization of the middle turbinate, concha bullosa, a variant of the development of ethmoidal cells, is the most commonly observed. Clinical practice suggests a close correlation between concha bullosa, mucosal contacts and rhinogenic headache, with high impact on the QoL. However diagnostic and therapeutic difficulties still remain. Aim of the present study is to evaluate the impact of medical or surgical care on the QoL of patients suffering from concha bullosa related headache from the patients' perspective. PATIENTS AND METHODS: One-hundred-two subjects with concha bullosa and headache anamnesis were randomized into two groups and given medical or surgical treatment. To assess the Quality of life (QoL) we used visual analogue scale and for the first time, the migraine disability score before and after treatment. RESULTS: After treatment the severity of the headache decreased as well as the discomfort in the surgical group compared with medical group. CONCLUSIONS: The improvement of symptoms and QoL suggests that the endoscopic surgical plastic may promote the rapid resolution of concha bullosa related headache improving the and reducing health care costs.

Cranial Nerve Abnormalities in Oculo-Auriculo-Vertebral Spectrum.

BACKGROUND AND PURPOSE: Cranial nerve abnormalities might be observed in hemifacial microsomia and microtia (oculo-auriculo-vertebral spectrum), but the rate, features, and relationship with functional impairment or phenotype severity have not yet been defined. This study aimed at investigating absence/asymmetry, abnormal origin, morphology and course of cranial nerves, and presence/asymmetry of the foramen ovale and inferior alveolar nerve canal in a cohort of oculo-auriculo-vertebral spectrum patients. MATERIALS AND METHODS: Twenty-nine patients with oculo-auriculo-vertebral spectrum (mean age, 7 years; age range, 0.2-31 years; 12 females) underwent brain MR imaging, CT, and neurologic evaluation; 19 patients had a more severe phenotype (Goldenhar syndrome). RESULTS: Cranial nerve abnormalities were detected only in patients with Goldenhar syndrome (17/19, bilaterally in 8) and were involved the second (4/19), third (1/18), fifth (11/19), sixth (8/16), seventh (11/18), and eighth (8/18) cranial nerves. Multiple cranial nerve abnormalities were common (11/17). Eleven patients showed bone foramina abnormalities. Trigeminal and facial nerve dysfunctions were common (44% and 58%, respectively), especially in patients with Goldenhar syndrome. Trigeminal abnormalities showed a good correlation with ipsilateral dysfunction (P = .018), which further increased when bone foramina abnormalities were included. The facial nerve showed a trend toward correlation with ipsilateral dysfunction (P = .081). Diplopia was found only in patients with Goldenhar syndrome and was associated with third and sixth cranial nerve abnormalities (P = .006). CONCLUSIONS: Among patients with oculo-auriculo-vertebral spectrum, cranial nerve morphologic abnormalities are common, correlate with phenotype severity, and often entail a functional impairment. The spectrum of cranial nerve abnormalities appears wider than simple hypo-/aplasia and includes an anomalous cisternal course and partial/complete fusion of diverse cranial nerves.

Brain anatomical substrates of mirror movements in Kallmann syndrome.

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.

Nasal cytological assessment after crenotherapy in the treatment of chronic rhinosinusitis in the elderly.

Chronic rhinosinusitis (CRS) determines irreversible alterations of the nasal mucosa with consequent impairment of ciliary movements and, therefore, mucociliary clearance (MCC). People of all ages can be affected by CRS but the elderly are subjects at the highest risk. CRS in the elderly with an age-related physiological impairment of nasal respiratory function, often accompanied by other chronic diseases, requires additional therapies to be added to the numerous daily medications. Since the currently available therapies for CRS include the use of drugs that can have adverse effects and contraindications, crenotherapy could represent a therapeutic option. Indeed, because the adverse effects and contraindications of crenotherapy are scarce, it can be safely used in elderly patients with comorbidities. The aim of this study is to evaluate the nasal cytological assessment after crenotherapy in elderly subjects with CRS. Two groups, comprising a total of 84 elderly subjects with CRS, were treated with crenotherapy with sodium chloride sulphate hyperthermal water rich in mineral salts (group I, n=49) and saline solution (group II n=35). Cytological assessment for both groups took place at baseline (T0) and 1 month after treatment (T30). At T30 the nasal cytological assessment showed statistically significant improvements in the ciliary motility and in the count of neutrophils and spores in group I, but not in group II. Conversely, there were no significant differences in the count of eosinophils, mast cells, bacteria and biofilm in either group. Our data for the first time focused on the role of crenotherapy in the improvement of cytological assessment of CRS in the elderly.

Management of otolaryngological manifestations in mucopolysaccharidoses: our experience.

Mucopolysaccharidoses (MPSs) are lysosomal storage disorders caused by deficiency of enzymes involved in the degradation of glycosaminoglycans (GAGs). These disorders are associated with the accumulation of GAGs in tissues with organomegaly, mental retardation and short stature. Otologic and upper respiratory tract pathologies are among the earliest clinical manifestations. We analyzed 20 patients (13 male and 7 female, median age at the beginning of the observation 6 years) with MPS (35% type I, 30% type II, 20% type III, 5% type IV, 10% type VI), focusing on their otorhinolaryngologic problems and the impact of surgery on quality of life. We found ear, nose and throat manifestations in all types of MPS; in particular, recurrent otitis media was present in 30% of cases, hearing loss in 75% (mixed in 43.33%, conductive in 43.33%, sensorineural in 13.33%), adenotonsillar hypertrophy in 75%, frequent infections of the upper airway in 75% and obstructive sleep apnoea syndrome in 45% of cases. Fifty percent of patients required surgical therapy (adenotonsillectomy, adenoidectomy with insertion of middle ear ventilation tubes, tonsillectomy, tracheotomy and exeresis of vocal cord polyps). In our experience the ENT surgery reduced the frequency and severity of ear infections and relieved symptoms related to upper airway obstruction, thereby improving the quality of life in affected patients.