Biofilm in voice prosthesis: A prospective cohort study and laboratory tests using sonication and SEM analysis.

OBJECTIVE: The objective of the study was to compare the biofilm growing pattern and its morphological extent on silicone and a teflon-like material using a sonication process and a Scanning Electron Microscope (SEM). DESIGN: A prospective cohort study and a laboratory study. SETTING: Otolaryngology -Head and Neck surgery Department and the Microbiology Institute. PARTICIPANTS: The participants included fifteen laryngectomised patients with phonatory prostheses, which were removed because of device failure, and two different kinds of phonatory prostheses from the laboratory (Provox 2 and ActiValve) that were artificially colonised by Candida albicans. MAIN OUTCOME MEASURES: Tracheo-oesophageal puncture (TEP) is currently considered the gold standard for post-laryngectomy voice rehabilitation. "Leakage" represents the most common cause of substitution and is generated by biofilm colonisation of the prosthesis by mixed mycotic and bacterial agents. New biomaterials have been developed that are deemed to be more resistant to the colonisation of micro-organisms and material deformation. RESULTS: The devices showed colonisation by mixed bacterial flora (Staphylococci 13%, Streptococci 9%, and Haemophilus influenzae 5%) and by yeasts (Candida albicans 12%). Moreover, we observed a different distribution of biofilm layers in Provox ActiValve (22.56%) compared to Provox 2 (56.82%) after experimental colonisation by the previously isolated Candida strain. CONCLUSION: Resident microbiological species from the upper airways unavoidably colonise the polymer surfaces, and no strategies have been effective except for the manipulation of the chemical-physical properties of the device's polymer. Our study confirms that Provox ActiValve, which is made with a fluoroplastic material (teflon-like), is less subject to in vitro colonisation by Candida, and thus showed a higher clinical resistance to biofilm and a longer lifespan. The sonication seems to significantly improve the knowledge of bacterial and mycotic flora in biofilm colonisation. The design of a device for the daily cleaning capable to reach and brush the oesophageal flange of the prosthesis preserving the valve mechanism could represent a practical and simple help in this still unsolved problem.

Idiopathic SIADH in young patients: don't forget the nose.

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine sinonasal cancer associated by many authors to ectopic production of several biologically active substances. We report a case of a 31-year-old male patient who presented with idiopathic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). During diagnostic work-up, a CT scan of the head was performed and an ethmoidal ONB was detected. Endoscopical surgery followed by radiotherapy was carried out. Immediately after surgery natraemia levels normalised. Five years later the patient is disease-free. To our knowledge, 17 cases of SIADH associated to ONB have been published. In nine reports, idiopathic SIADH promptly led to the diagnosis of the sinonasal mass as in our clinical case, however, in many reports, correct diagnosis was accomplished months to years later. In young patients with idiopathic inappropriate antidiuretic hormone secretion, a neuroendocrine malignancy of the sinonasal area must be excluded.

Rentabilidad diagnóstica y complicaciones de la linfadenectomía ampliada frente a la limitada asociada a prostatectomía radical / Diagnostic yield and complications of extended lymphadenectomy versus limited lymphadenectomy combined with radical prostatectomy

Introducción: La linfadenectomía en el cáncer de próstata (CP) es el procedimiento más fiable para la detección de metástasis linfáticas. La extensión óptima de la misma aún es un tema en debate. Objetivo: Analizar el rendimiento diagnóstico y las complicaciones de la linfadenectomía ampliada (LFDNA) y limitada (LFDNL) en una serie de pacientes con CP de alto riesgo sometidos a prostatectomía radical (PR). Material y métodos: Estudio retrospectivo de pacientes con CP de alto riesgo de D’Amico sometidos a PR con linfadenectomía entre 1999- 2014. Análisis comparativo de la capacidad de diagnóstico de metástasis linfáticas de la LFDNA y LFDNL y de las complicaciones postoperatorias a 90 días. Resultados: Se analizaron 93 pacientes, 20 (21,5%) sometidos a LFDNA y 73 (78,5%) a LFDNL. La edad media de la serie fue de 65,26 años (DE 5,51). La mediana de seguimiento fue de 1,51 (0,61-2,29) años en el grupo de LFDNA y 5,94 (3,61-9,10) en LFDNL. La mediana de ganglios obtenidos fue de 13 (9-23) en las LFNDA vs. 5 (2-8) en las limitadas (p < 0,001) y el porcentaje de pacientes con ganglios positivos obtenidos fue de 35 y 5,47% respectivamente (p < 0,001). El porcentaje global de complicaciones a 90 días fue 35,5% (33 pacientes). Del grupo de LFDNA 12 pacientes (60%) presentaron complicaciones, frente a 21 (28,8%) en LFDNL (p = 0,016), sin encontrar diferencias significativas en la gravedad según la escala de Clavien (p = 0,73). Conclusiones: En nuestra serie, la detección de ganglios metastásicos ha sido significativamente superior en la LFDNA. La LFDNA aumenta el número de complicaciones, sin encontrar diferencias con la LFDNL en la gravedad según la escala de Clavien modificada

Background: Lymphadenectomy for prostate cancer (PC) is the most reliable procedure for detecting lymphatic metastases. The optimal extension of this procedure is still a topic of debate. Objective: To analyse the diagnostic performance and complications of extended lymphadenectomy (ELD) and limited lymphadenectomy (LLD) in a series of patients with high-risk PC who underwent radical prostatectomy (RP). Material and methods: A retrospective study was conducted on patients with high d’Amico risk who underwent RP with lymphadenectomy between 1999 and 2014. A comparative analysis was performed of the diagnostic capacity of lymphatic metastases of ELD and LLD and of postoperative complications at 90 days. Results: Ninety-three patients were analysed, 20 (21.5%) and 73 (78.5%) of whom underwent ELD and LLD, respectively. The mean age of the series was 65.26 years (SD, 5.51). The median follow-up was 1.51 (0.61–2.29) years in the ELD group and 5.94 (3.61–9.10) in the LLD group. The median number of nodes obtained was 13 (9–23) in the ELD group compared with 5 (2–8) in the LLD group (p < .001). The percentages of patients with positive nodes in the ELD and LLD groups were 35% and 5.47%, respectively (p < .001). The overall complication rate at 90 days was 35.5% (33 patients). In the ELD group, 12 patients (60%) had complications, compared with 21 patients (28.8%) in the LLD group (p = .016), with no significant differences in severity according to the Clavien scale (p = .73). Conclusions: In our series, the detection of metastatic nodes was significantly greater with ELD. ELD increases the number of complications, with no differences compared with LLD in severity according to the modified Clavien scale

Diagnostic yield and complications of extended lymphadenectomy versus limited lymphadenectomy combined with radical prostatectomy.

BACKGROUND: Lymphadenectomy for prostate cancer (PC) is the most reliable procedure for detecting lymphatic metastases. The optimal extension of this procedure is still a topic of debate. OBJECTIVE: To analyse the diagnostic performance and complications of extended lymphadenectomy (ELD) and limited lymphadenectomy (LLD) in a series of patients with high-risk PC who underwent radical prostatectomy (RP). MATERIAL AND METHODS: A retrospective study was conducted on patients with high d'Amico risk who underwent RP with lymphadenectomy between 1999 and 2014. A comparative analysis was performed of the diagnostic capacity of lymphatic metastases of ELD and LLD and of postoperative complications at 90 days. RESULTS: Ninety-three patients were analysed, 20 (21.5%) and 73 (78.5%) of whom underwent ELD and LLD, respectively. The mean age of the series was 65.26 years (SD, 5.51). The median follow-up was 1.51 (0.61-2.29) years in the ELD group and 5.94 (3.61-9.10) in the LLD group. The median number of nodes obtained was 13 (9-23) in the ELD group compared with 5 (2-8) in the LLD group (p <.001). The percentages of patients with positive nodes in the ELD and LLD groups were 35% and 5.47%, respectively (p <.001). The overall complication rate at 90 days was 35.5% (33 patients). In the ELD group, 12 patients (60%) had complications, compared with 21 patients (28.8%) in the LLD group (p=.016), with no significant differences in severity according to the Clavien scale (p=.73). CONCLUSIONS: In our series, the detection of metastatic nodes was significantly greater with ELD. ELD increases the number of complications, with no differences compared with LLD in severity according to the modified Clavien scale.

Patients' experiences with HMEs and attachments after total laryngectomy.

OBJECTIVES: The short-term and long-term beneficial effects of HME use by laryngectomees are well described in literature. In this study, we document how laryngectomised patients, who previously did not use an HME, get accustomed to the use of HME and attachments. PARTICIPANTS: Thirty patients, who were at least 3 months post-laryngectomy and previously did not use an HME, were followed for 12 weeks and were asked to complete questionnaires about their experiences with the HME and attachments. RESULTS: Results show that when patients start using an HME, they report some difficulties with breathing resistance during the first 2 weeks of use. However, after 6 weeks, they have become accustomed to the breathing resistance and after 12 weeks over 96% reports that breathing was equal or less strenuous compared with breathing though an open stoma. Only a small proportion of patients experienced problems with increased coughing when starting HME use. CONCLUSIONS: This study provides insight in the way laryngectomised patients are experiencing the use of HMEs in the first weeks. These outcomes can contribute to a better knowledge of HME use by healthcare providers and help them to manage patient expectations and improving support to patients in achieving compliant HME use.

Impact of microvascular free flap reconstruction in oral cavity cancer: our experience in 130 cases.

The aim of this study was to investigate the oncological outcomes in patients affected by oral carcinoma treated with radical compartmental surgery followed by microvascular flap reconstruction. We conducted a retrospective analysis on a cohort of 130 patients. All patients underwent ablative tumour resection (compartmental surgery) followed by immediate reconstruction with free flaps and adjuvant chemoradiotherapy, when necessary according to our tumour board and international guidelines. Disease-specific survival (DSS) curves were obtained using the Kaplan-Meier method. Log-rank test and generalised Wilcoxon test were used to investigate the most important prognostic factors on 5-year DSS. A Cox proportional hazards model was constructed to provide hazard ratios or relative risks for individual variables. 88.5% of patients were affected by SCC. There were 46 (35.4%) women and 84 (64.6%) men in the sample with a mean age of 58.5 years. At the end of the follow-up period, 36 (27.7%) patients died, only 3 of which for other causes. The 5-year DSS rate was 67.8% (S.E. 4.9%). In univariate Kaplan-Meier analysis and in multivariate Cox regression model, seven variables were found to have a significant relationship with DSS: T (p = 0.026) and N (p = 0.0001) status, clinical stage (according to the UICC TNM Sixth Edition) (p = 0.007), margins of resection (p = 0.001), extracapsular spread (p = 0.005), recurrence of disease (p = 0.00002) and treatment modality (evaluated as surgery alone or surgery + RT/CHT) (p = 0.004). Our results confirmed findings already reported in the literature, and allowed us to conclude that compartmental surgery combined with free flap reconstruction can increase survival in oral cancer patients.

Differential diagnosis of parotid gland tumours: which magnetic resonance findings should be taken in account?

Our aim was to define typical magnetic resonance (MRI) findings in malignant and benign parotid tumours. This study is based on retrospective evaluation of pre-surgical MRI of 94 patients with parotid gland tumours. Histology results were available for all tumours. There were 69 cases of benign (73%) and 25 cases of malignant (27%) tumours, including 44 pleomorphic adenomas, 18 Warthin's tumours, 7 various benign tumours, 6 squamous cell carcinomas, 3 carcinoma ex pleomorphic adenomas, 2 mucoepidermoid carcinomas, 1 adenoid cystic carcinoma and 13 various malignant tumours. The following MRI parameters were evaluated: shape, site, size, margins, signal intensity (SI) on T1w and T2w images, contrast enhancement, signal of cystic content, presence or absence of a capsule, perineural spread, extraglandular growth pattern and cervical adenopathy. Statistical analysis was performed to identify the MRI findings most suggestive of malignancy, and to define the most typical MRI pattern of the most common histologies. Ill-defined margins (p < 0.001), adenopathies (p < 0.001) and infiltrative grown pattern (p < 0.001) were significantly predictive of malignancy. Typical findings of pleomorphic adenoma included hyperintensity on T2w images (p = 0.02), strong contrast enhancement (p < 0.001) and lobulated shape (p = 0.04). Typical findings of Warthin's tumour included hyperintense components on T1w images (p < 0.001), location in the parotid inferior process (p < 0.001) and mild or incomplete contrast enhancement (p = 0.01). SI on T1w and T2w images and contrast enhancement enables differential diagnosis between pleomorphic adenoma and Warthin's tumour.

Effects of heat and moisture exchangers on tracheal mucociliary clearance in laryngectomized patients: a multi-center case-control study.

After total laryngectomy, inspired air is no longer optimally conditioned by the upper airways. Impaired mucociliary clearance and histological changes of respiratory epithelium, such as loss of ciliated cells, have been described in laryngectomized patients. Heat and moisture exchangers (HMEs) are passive humidifiers that re-condition the inspired air. Aim of this study was to assess the effect of HMEs on tracheal epithelium and tracheal mucus transport velocity (TMV). Tracheal brush biopsies were collected in three groups of TLE patients: 21 long-term HME users, 10 non-HME users, and 16 non-HME users before and after 4-9 months HME use. Tracheal epithelium biopsies were assessed using a digital high-speed camera mounted onto a light microscope. TMV was determined by scintigraphy in the first two patient groups. Significantly more ciliated cells were found in HME users compared to non-HME users (p = 0.05). TMV was higher in HME users (median 2 mm/min; 0-7.9) compared to non-HME users (median 0.8 mm/min; 0-12.3), but this difference was not significant (p = 0.37). One-hour breathing without HME in long-term HME users did not measurably decrease TMV (p = 0.13). The long-term use of an HME restores/prevents the loss of tracheal ciliated cells. A significant improvement in TMV was not found. Short-term (one hour) detachment of an HME has no measurable effect on TMV.

The role of septal surgery in cosmetic rhinoplasty.

Septoplasty is performed to resolve breathing problems, but it often becomes pivotal to correct external nasal deviation, representing a central step in rhinoplasty surgery. Even in patients with no functional problems, septal surgery may represent the best solution for obtaining a proper realignment of the external nasal pyramid. One-stage septorhinoplasty has become the standard of treatment for a deviated nose, hence septoplasty cannot be considered as a separate procedure to perform before or after rhinoplasty or as a partial operation subject to later revision. The aim of this article is to discuss the close relationship between the nasal septum and the aesthetics of the nose, and how a graduated surgical approach for the correction of septal deviations could affect the external deviated nose.

Clinical approach and treatment of benign and malignant parotid masses, personal experience.

Parotid gland tumours account for 80% of all salivary gland neoplasms, 20% of these are malignant, but in daily clinical practice most parotid masses are operated on before obtaining the final histological diagnosis. This clinical setting further complicates the critical point of parotid surgery, which is the management of the facial nerve. In the present study, data were evaluated referring to 540 patients who underwent parotidectomy for a mass which was discovered to be a benign (470 cases) or a malignant (70 cases) neoplasm, between November 1994 and December 2007, at our Institution. The most significant single parameter in this series of malignancies regarding disease specific survival was the clinical involvement of the facial nerve at diagnosis (p = 0.006). Also for this reason, as there is no evidence that liberal VIIth nerve sacrifice improves prognosis, when it is not clinically involved, every attempt is made to dissect and preserve it. At present, the most complicated situation concerning nerve preservation may be, on the other hand, recurrence of a benign tumour, in particular pleomorphic adenoma, which, in our series, has a higher incidence (8.3%) of permanent facial dysfunction, than surgery with nerve preservation for malignancy (3.7%).

Oral cavity defect reconstruction using anterolateral thigh free flaps.

BACKGROUND: It is estimated that about 92,000 new cases of oral cavity and pharyngeal cancer occurred in Europe in 2008. During the past 30 years in the USA and Western Europe, the prognosis for oral cancer has clearly improved thanks to the possibility of reconstruction with microvascular free flaps, resulting in broader and safer resections. The anterolateral thigh flap is now being increasingly employed for this goal. The aim of the present work is to evaluate the anterolateral thigh free flap in the reconstruction of oral cavity defects. MATERIALS AND METHODS: Between July 2004 and February 2009, we harvested 73 free flaps for the reconstruction of soft tissue defects in the oral cavity of 70 patients at our institution. The oncological and functional results in these 70 patients were evaluated, particularly in those patients reconstructed with anterolateral thigh (ALT) free flap. We also evaluated the quality of life using the FACT-H&N questionnaire. RESULTS: We observed no significant differences in functional and oncological results between patients reconstructed by ALT and patients reconstructed with other flaps. Swallowing may be more difficult in patients who undergo adjuvant irradiation. CONCLUSIONS: In our opinion, the very low morbidity at the donor site, great versatility, and very long pedicle make the ALT free flap the first choice for reconstructing soft tissue defects in the oral cavity (particularly mobile tongue).

Overlay versus underlay myringoplasty: report of outcomes considering closure of perforation and hearing function.

In this series of patients, the underlay or overlay positioning of a graft achieves successful outcome for both repair of perforation and hearing function, with better hearing gain in the underlay group. In myringoplasty, the two most common techniques for positioning the graft relative to the remnant of both the tympanic membrane and the annulus are the "overlay" and the "underlay" techniques. 115 patients who underwent myringoplasty for tympanic membrane perforation secondary to chronic otitis media and/or trauma were included, and hearing function was evaluated. We prefer an overlay technique in subtotal perforations, in those involving the anterior and antero-inferior parts of the ear drum with respect to the handle of the malleus and in revision surgery. We reserve an underlay technique for smaller perforations and for those limited to the posterior part of the tympanic membrane. Of 115 cases, 63 underwent an overlay myringoplasty and 52 underlay myringoplasty. In the former group, five cases were anatomically unsuccessful, whereas in the second group there were three failures. The air bone gap improved significantly in both groups with a better hearing gain in the underlay group.

Cochlear implant patients' speech understanding in background noise: effect of mismatch between electrode assigned frequencies and perceived pitch.

OBJECTIVE: To assess the electrode pitch function in a series of adults with postlingually implanted cochlear implants and with contralateral residual hearing, in order to investigate the correlation between the degree of frequency map mismatch and the subjects' speech understanding in quiet and noisy conditions. DESIGN: Case series. SUBJECTS: Seven postlingually deafened adults with cochlear implants, all with detectable contralateral residual hearing. Subjects' electrode pitch function was assessed by means of a pitch-matching test, in which they were asked to match an acoustic pitch (pure tones delivered to the non-implanted ear by an audiometer) to a perceived 'pitch' elicited by stimulation of the cochlear implant electrodes. A mismatch score was calculated for each subject. Speech recognition was tested using lists of sentences presented in quiet conditions and at +10, 0 and 5 dB HL signal-to-noise ratio levels (i.e. noise 10 dB HL lower than signal, noise as loud as signal and noise 5 dB HL higher than signal, respectively). Correlations were assessed using a linear regression model, with significance set at p < 0.05. RESULTS: All patients presented some degree of mismatch between the acoustic frequencies assigned to their implant electrodes and the pitch elicited by stimulation of the same electrode, with high between-individual variability. A significant correlation (p < 0.005) was found between mismatch and speech recognition scores at +10 and 0 dB HL signal-to-noise ratio levels (r2 = 0.91 and 0.89, respectively). CONCLUSION: The mismatch between frequencies allocated to electrodes and the pitch perceived on stimulation of the same electrodes could partially account for our subjects' difficulties with speech understanding in noisy conditions. We suggest that these subjects could benefit from mismatch correction, through a procedure allowing individualised reallocation of frequency bands to electrodes.

Multiple viral genome search in endolabyrinthic fluids of profoundly deaf patients: possible cytomegalovirus intracochlear reactivation.

BACKGROUND: The cause of about 30% of bilateral sensorineural hearing loss (SNHL) is still unknown. A viral etiology is among the most frequently proposed ones and the supposed diagnosis is only based upon few clinical and laboratory data. The detection of viral presence within a damaged compartment may represent a way to supply interesting data for confirmation of viral etiology and to explain pathogenic mechanisms. OBJECTIVES: The aim of our study was to identify the possible presence of pathogenic viruses in the inner ear extracellular compartment in patients with bilateral severe sensorineural deafness of unknown etiology who underwent cochlear implant surgery. METHODS: 4 patients, aged from 2 to 7 years and affected by SNHL underwent cochlear implantation surgery and, at the same time, endolabyrinthine fluid sampling. The samples were subsequently sent for viral nucleic acid extraction and polymerase chain reaction (PCR) treatment: multiplex PCR and realtime-PCR were used. In each endolabyrinthine fluid sample, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), herpes simplex virus type 1 and 2 (HSV-1, HSV-2) and enterovirus genomes were searched for. RESULTS: One patient was positive for intracochlear CMV, as confirmed by another base-pair segment PCR. EBV, VZV, HSV and enterovirus were detected in none of the 4 patients. CONCLUSIONS: Our finding of CMV genome within the cochlea of a deaf patient without any evidence of acute and prenatal CMV infection suggests its possible role in postnatal inner ear injury through reactivation of latent virus within the cochlea. This hypothesis could also be considered valid for some patients with anti-CMV-IgG-positive serology and absence of endolabyrinthine viral genome since viruses can be in an inactive state at the time of fluid collection. PCR has proved to be a very useful tool in order to investigate infectious causes of deafness even for more than one virus type at a time and in a limited quantity of sample, such as the small volume of endolabyrinthine liquid collected from children during cochlear implant surgery.

Pharyngocutaneous fistula onset after total laryngectomy: scintigraphic analysis.

Pharyngocutaneous fistula is the most common non-fatal complication following total laryngectomy. To start oral feeding and exclude the presence of a pharyngocutaneous fistula, a subjective test and instrumental assessments using videofluoroscopy, have been described. The aim of this study was to evaluate the effectiveness of oral-pharyngo-oesophageal scintigraphy as an objective and non-invasive tool to establish presence, site and dimensions of the fistula. Observations were performed on 3 male patients, mean age 65 years, who underwent total laryngectomy and mono or bilateral neck dissection after failure of radiotherapy in 2 cases and of conservative laryngeal surgery in the third case, complicated by post-operative pharyngocutaneous fistula. Oral-pharyngo-oesophageal scintigraphy dynamic study with sequential images were obtained during the swallowing phases. In case 1, the test showed a wide pharyngocutaneous fistula the internal orifice of which was at the level of the base of the tongue: on the scintigraphic images, the radiomarked water bolus, from the fistulous orifice, descended along the stoma walls and only a small part reached the oesophagus. In the other two patients, the pharyngocutaneous fistula was small and the internal fistulous orifice was detected in the lower part of T-suture line. In conclusion, scintigraphy offered the possibility to precisely identify presence of pharyngocutaneous fistula and location of its internal orifice and to monitor its spontaneous closure. Therefore, important information could be obtained regarding the suture line status and the possibility of deciding whether to remove the nasogastric tube or to leave it in place. Finally, these data showed that oral-pharyngo-oesophageal scintigraphy could be performed in the early post-operative period to optimize starting safe oral feeding.

Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs.

Increasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elevation ranging between 12 and 16 kHz. During the first 24 h, following acoustic trauma, there was a partial recovery of compound action potential thresholds of about 20 dB to reach a final threshold elevation of about 50-70 dB; there was no further improvement over the remaining experimental week. Animals treated with N-acetylcysteine showed a similar temporary threshold shift but a clear improvement in the recovery of compound action potential thresholds, with significantly reduced permanent threshold shift and hair cell loss. These data suggest that N-acetylcysteine is able to attenuate the toxic effect of acoustic trauma and could represent an interesting molecule for preventing inner ear injuries.

Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models.

Local gene transfer of the human Lim mineralization protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. To develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP-3 and seeded on a hydroxyapatite/collagen matrix prior to autologous implantation. Here, we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing, as determined by X-rays, histology and three-dimensional microcomputed tomography (3DmuCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3 in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.

High resolution magnifying endoscopy: a new diagnostic tool also for laryngeal examination?

Aim of this report is to introduce the use of a new high resolution magnifying endoscope in the endoscopic examination of the upper aerodigestive tract and discuss the usefulness of this tool in the diagnosis of laryngeal lesions. A total of 26 patients presenting various laryngeal disorders were examined by means of an electronic videoendoscope and a high resolution magnifying endoscope. The images obtained were examined and compared. High resolution high magnification endoscopic examination allowed a better description of the laryngeal lesions (colour, extension and thickness of the lesion, irregularities in surface and borders) with easy characterisation of aspect of neighbouring laryngeal mucosa especially in pre-malignant lesions. Furthermore, the optical magnifying zoom does not require a close approach to the laryngeal mucosa, therefore, local anaesthesia is not required. In conclusion, the high resolution magnified images obtained with this new tool provide important information on the characteristics of the laryngeal structures. This new endoscopic technology, as already occurred in gastric, oesophageal and colorectal disorders, could also be improved by using chromo-endoscopy and other vital stain techniques in order to provide useful information concerning pre-neoplastic lesions of the larynx.