[Confocal laser endomicroscopy - first application and validation of malignancy criteria]. / Endonasale konfokale Laserendomikroskopie ­ erste Anwendung und Validierung von Malignitätskriterien.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. First investigations on head and neck carcinoma described the oropharyngeal application. The aim of this investigation is to elucidate, based on the criteria validated in the oropharynx, whether these can be transferred to endonasal mucosa. METHODS: CLE was performed with intravenous fluorescein staining in endoscopic sinus surgery in one patient with sinonasal inverted papilloma and another with squamous cell carcinoma. We compared cellular visualization of pathological changes to those of healthy mucosa in the same specimen as well to our former findings in the oropharynx. RESULTS: Endonasal CLE proved to be well feasible in the surgical setting and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. CONCLUSION: Our results suggest that endonasal CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses. Further investigation and validation will be necessary.

An acute exposure to ozone impairs human olfactory functioning.

INTRODUCTION: Ozone is a ubiquitous and irritant gas. We questioned whether an acute exposure to 0.2 ppm ozone impaired olfactory functioning. METHODS: Healthy, normosmic subjects were exposed according to a parallel group design either to 0.2 ppm ozone (n = 15) or to sham (n = 13) in an exposure chamber for two hours. Possible irritating effects were assessed by questionnaire (range 0-5). The detection threshold of n-butanol was measured with the Sniffin' Sticks test before and after exposure. Olfactory thresholds were logarithmized and a two-way analysis of variance (ANOVA) with repeated measurements was carried out to test the effects of exposure (ozone vs. sham) and time (before vs. after exposure). Additionally, nasal secretions were taken at a preliminary examination and after exposure to determine interleukins 1ß and 8. RESULTS: No irritating effects to the upper airways were observed. In the ozone group, the median score for cough increased from 0 to 2 at the end of exposure (sham group 0 and 0, respectively, p < 0.001). The ANOVA showed a main effect for ozone exposure (F (1, 26) = 27.6, p = 0.0002), indicating higher olfactory thresholds in the ozone group. Concentrations of interleukins in nasal secretions did not increase following ozone exposure. CONCLUSIONS: This study shows a clear impairment of olfactory functioning following an acute exposure to 0.2 ppm ozone.

Confocal Laser Endomicroscopy in Resection of Sinonasal Malignant Melanoma-Preliminary Report on Real-Time Margin Assessment and Support in Surgical Decision-Making.

Background/Objectives: Building upon the rising value of Confocal Laser Endomicroscopy (CLE) in squamous cell carcinoma of the head and neck, we present the first application of CLE during the resection of sinonasal malignant melanomas. This study aims to evaluate the potential of CLE to assist surgeons in intraoperative decision-making, with a particular focus on resection margin assessment within the constrained nasal cavity. Methods: Two cases of sinonasal malignant melanoma were included in this study. CLE was employed to examine visible tumors and their margins, both pre- and post-endoscopic resection. The findings were compared to histopathological results as well as data on squamous cell carcinoma, for which malignancy criteria had already been established in prior projects. Results: CLE provided the real-time visualization of sinonasal malignant melanomas and their margins, successfully differentiating between healthy and neoplastic tissue compared to histopathological findings. Conclusion: CLE offers the potential for real-time assessment, aiding surgeons in more precise tumor resection and potentially improving patient outcomes. This study demonstrates the feasibility of using CLE in the resection of sinonasal malignant melanoma, highlighting its ability to differentiate between healthy and neoplastic tissue intraoperatively.

Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

The Multifaceted Role of Confocal Laser Endomicroscopy in Head and Neck Surgery: Oncologic and Functional Insights.

(1) Background: Confocal laser endomicroscopy (CLE) has emerged as a transformative tool in head and neck surgery, with applications spanning oncologic insights and functional evaluations. This study delves into CLE's potential in these domains. (2) Methods: We performed CLE in head and neck oncologic surgery, focusing on tumor margin identification and precise resection. We also employed CLE for functional assessment in allergic rhinitis, observing real-time mucosal changes during nasal provocation testing. (3) Results: In oncologic surgery, CLE enabled real-time visualization of tumor margins and cellular patterns, aiding resection decisions. In allergic rhinitis assessment, CLE captured dynamic morphological alterations upon allergen exposure, enhancing understanding of mucosal reactions. (4) Conclusions: The integration of CLE with evolving technologies such as deep learning and AI holds promise for enhanced diagnostic accuracy. This study underscores CLE's expansive potential, highlighting its role in guiding surgical choices and illuminating inflammatory processes in the head and neck.

Technical Note: First Use of Endonasal Confocal Laser Endomicroscopy - Feasibility and Proof of Concept.

Introduction Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses. Further investigation and validation will be necessary.

Confocal endomicroscopy: a novel application for imaging of oral and oropharyngeal mucosa in human.

Confocal endomicroscopy is an emerging technique for intravital visualization of neoplastic lesions, but its use has so far been limited to the gastrointestinal (GI) tract. This study was designed to assess the feasibility of in vivo confocal endomicroscopy of different regions of the oropharyngeal mucosa and to evaluate different contrast agents. We examined five different regions of the human oropharynx in vivo, and images were collected in real time by using a confocal laser endoscope as formerly described for the GI tract. Additionally ex vivo specimens were examined using a topical contrast agent. Confocal scanning was performed at 488-nm illumination for excitation of exogenously applied fluorophores (topical acriflavine and intravenous fluorescein). Confocal endomicroscopy allowed for visualization of cellular and subcellular structures of the anterior human oropharyngeal region. Fluorescein staining yielded architectural details of the surface epithelium and also subepithelial layers. Images taken at increasing depth beneath the epithelium showed the mucosal capillary network. Acriflavine strongly contrasted the cell nuclei of the surface epithelium. The findings correlated well with the histology of biopsy specimens. This is the first report showing that the use of fluorescence confocal endomicroscopy represents a promising method to examine cellular details in vivo in different oropharyngeal regions in human.

Cochlear implant and hearing aid: a new approach to optimizing the fitting in this bimodal situation.

More and more patients with residual hearing on the contralateral side are becoming candidates for cochlear implants (CI) surgery due to increasing CI. The major benefits of regular binaural hearing are spatial hearing, localization, and signal source discrimination in both quiet and noisy surroundings. In most of the reports, hearing aid fitting was carried out without balancing both the devices. Twelve children and eight adults with residual hearing on the non-operated side were binaurally fitted. Our fitting procedure for the hearing aid was based on the desired sensation level [i/o] method. A loudness scaling was used to adjust the loudness perception monaurally and to balance the volume of both devices. Speech audiometry in quiet and noisy surroundings was conducted both monaurally and in the bimodal mode. The fitting was modified according to the respective test results. In all children and six adults, a measurable gain and/or a subjective improvement of speech perception was achieved. Two adult patients did not accept the new fitting. In seven younger children, loudness scaling was impossible to perform because of age. This was also the case with speech audiometry for two children. A structured bimodal fitting using loudness scaling for both the cochlear implant and the hearing aid results in a subjective and objective amelioration of the patient's hearing and speech perception.

Analysis of fifty-six cochlear implant device failures.

OBJECTIVE: Our aim was to present a failure analysis after cochlear implant revision surgery in a large series of children and adults and to assess the outcome and audiologic performance. METHODS: Fifty-six cochlear implant failures that occurred in 422 devices implanted between 1990 and 2007 at the Department of Otolaryngology, Head and Neck Surgery at the University of Mainz, Germany, were retrospectively analyzed. The causes of failure were reviewed evaluating the individual history, telemetric and intraoperative findings and manufacturer's investigation reports. RESULTS: We performed 56 surgical revisions in a series of 422 consecutive implants (overall revision rate: 13.27%). The most frequent causes for revision were hard failures (58.9%), most commonly caused by traumatic impact (37.5%), especially in the pediatric population. Soft failures were less frequent (21.4%). Surgical reimplantations, although challenging in some cases, were performed without complications and with an electrode insertion depth comparable to that at the time of the initial implantation in all patients. The average audiologic performance improved by 2.4 dB in pure-tone perception levels after reimplantation. CONCLUSION: The cochlear implant failure rates vary between children and adults as well as between different implant manufactures. However, cochlear reimplantation is safe with excellent and predictable results in audiologic performance.

Polysomnography and ApneaGraph in patients with sleep-related breathing disorders.

PURPOSE: To evaluate whether ApneaGraph (AG) and polysomnography (PSG) deliver comparable results in patients with sleep-related breathing disorders. PROCEDURES: A prospective study was performed, which included 14 patients with obstructive sleep apnea syndrome. Apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), obstructive, central and mixed apnea, oxygen saturation (SaO2), pulse and body position were simultaneously assessed by PSG and AG in each individual. RESULTS: There was a good correlation between measurements of AG and PSG for AHI, pulse, SaO2, body position and central apnea. However, our study showed differences between PSG and AG for AI (p = 0.002), HI (p = 0.013), mixed apnea (p = 0.003) and obstructive apnea (p = 0.013). AG indicated that 2/14 patients had a pure upper airway obstruction, 6/14 patients had a predominance of lower obstruction and 6/14 patients had a predominance of upper obstruction. CONCLUSION: AG provides comparable results for AHI, pulse, SaO2, body position and central apnea when compared to PSG, but not for the rest of the measurements. Using AG, the distribution of sites of obstructive events could be identified in this study in all of the patients.

Histological and radiological signs indicative for chronic sinus mucosal inflammation in Graves' ophthalmopathy.

Orbital decompression and, in some cases, decompression of the optic nerve are the principal surgical procedures used for treatment of moderate or severe Graves' orbitopathy (GO). Histological examination of the surgical specimens of the ethmoid revealed a wide spectrum of inflammatory mucosal changes. The charts of 68 GO patients (55 female and 13 male; age range: 14 - 85 years) were retrospectively reviewed. Lund - Mackay scores were calculated for each patient based on findings of pre-operative computer tomography (CT) sinus scans, and the incidence of histological changes associated with polypoid and eosinophilic inflammation was assessed. Files did not reveal any evidence of chronic rhinosinusitis with or without nasal polyps based on endoscopic findings. Sinus opacification on CT (of any extent) was found in 20 out of the 68 patients (29.4%). On histological exam, histological changes of the sinus mucosa indicative for chronic rhinosinusitis were found in 31 out of the 68 GO patients (45.5%). A histological examination of the sinus mucosa indicative for chronic polypoid inflammation was present in 25 patients. Fourteen out of these 25 patients showed mucosal tissue eosinophilia on histology. Six patients had mucosal changes suggesting chronic non-polypoid inflammation with tissue eosinophilia on histological exam. The incidence of chronic rhinosinusitis in individuals without GO ranges between 10 and 15%. The incidence of histological changes of the sinus mucosa indicative for chronic rhinosinusitis described in this investigation suggests that chronic inflammatory disease is considerably more frequent in GO patients, when compared to the incidence of chronic rhinosinusitis in individuals without GO. Additionally, our data underline that CT imaging of the paranasal sinuses underestimates (29.4%) the incidence of inflammatory changes of the sinus mucosa (45.5%) of any extent in GO patients.

Fluorescein- and EGFR-Antibody Conjugated Silica Nanoparticles for Enhancement of Real-time Tumor Border Definition Using Confocal Laser Endomicroscopy in Squamous Cell Carcinoma of the Head and Neck.

Intraoperative definition of tumor free resection margins in head and neck cancer is challenging. In the current proof-of-principle study we evaluated a novel silica nanoparticle-based agent for its potential use as contrast enhancer. We synthesized silica nanoparticles with an average size of 45 nm and modified these particles with the fluorescence stain fluorescein isocyanate (FITC) for particle detection and with epidermal growth factor receptor (EGFR)-targeting antibodies for enhanced tumor specificity. The nanoparticles exhibited good biocompatibility and could be detected in vitro and in vivo by confocal laser scanning microscopy. Additionally, we show in an ex vivo setting that these modified nanoparticles specifically bind to tumor samples and could be detected using a handheld confocal fluorescence endomicroscope. From a clinical point of view, we believe that this method could be used for tumor border contrast enhancement and for better intraoperative definition of R-0 tumor resection.

Early stress response of human nasal respiratory epithelia after exposure to 1-methoxypropanol-2.

To evaluate the impact of 1-methoxypropanol-2 (MEP) for the stimulation of an inflammatory response in human respiratory mucosa, we exposed 22 primary cell cultures of nasal respiratory epithelia of healthy individuals to MEP concentrations at the level of the German MAK-value (100 ppm) and to the 10-fold concentration (1000 ppm). After 4 and 24h we analyzed the transcription of TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2 by quantitative PCR as well as the release of the respective cytokines by ELISA. At both MEP concentrations we observed a significant increase of TNF-alpha-, IL-1beta-, IL-6- and Cox-2-transcripts after 4h. After 24h cytokine transcription of TNF-alpha, IL-1beta and IL-6 was normalized, but Cox-2 remained elevated. On the protein level IL-1beta as well as granulocyte macrophages colony stimulating factor (GM-CSF) were decreased after 4h or 24h and uniquely IL-8 levels were increased after 4h. Our data suggest that MEP induces the transcription of genes encoding proinflammatory cytokines and mediators but largely not translation of those. Considering these in vitro data, existing exposure limits seem to be safe with respect to inflammatory responses of the upper respiratory tract. However, the effects of long-term exposures to MEP should be watched closely.

Characteristics of recurrent chronic rhinosinusitis after previous surgical therapy.

CONCLUSIONS: Our findings emphasize the role of a thorough diagnostic evaluation preoperatively and a targeted long-term medical therapy following any sinonasal surgery for inflammatory disease. Early onset of long-term aspirin desensitization can address a very predominant inflammatory stimulus in a large number of our patients in an effort to prevent recurrent chronic rhinosinusitis (CRS) after successful surgical therapy. BACKGROUND: Postoperative recurrence of CRS, regardless of the ongoing evolution of diagnostic and surgical techniques, still poses an unsolved problem. SUBJECTS AND METHODS: This investigation was designed to further characterize the role of aspirin intolerance (AI) and inhalant allergies as persistent inflammatory stimuli in the postoperative period and secondly to analyze the correlation between preoperative computed tomographic (CT) scores and the actual intraoperative findings. A total of 143 patients with recurrent CRS were included in this retrospective analysis, who all underwent revision sinus surgery at our institution after one or multiple previous operations. Charts were analyzed for the incidences of AI and inhalant allergies, CT scores, and intraoperative scores. RESULTS: In all, 66/143 patients had inhalant allergies and 55/143 were diagnosed with AI. The risk of recurrent CRS was found to be highest in the group with AI, along with the shortest interval between previous surgical interventions and the need for revision. In a subgroup of 34 cases, correlations between CT and intraoperative endoscopy scores were poor in 79%. Interestingly, at the time of recurrence the frontal sinuses were diseased in 17.6% of cases, where they had been healthy at the time of the initial intervention.

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

Frequent chromosomal gains in recurrent juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor, mostly affecting adolescent males. Some patients develop recurrences after surgery independently of completeness of removal. Only very limited data concerning underlying chromosomal changes are available. We therefore analyzed samples of 22 JNAs, including six recurrences, with comparative genomic hybridization (CGH). Additionally, quantitative image cytometry was used for measurement of DNA aneuploidy in representative samples. Of the 13 primary JNAs without later recurrence, DNA gains were identified on autosomes in only two samples. Four patients with one or two recurrences were included in the study; for one of these, no material of the primary tumor was available for analysis. Looking at autosomes, two of the three available primaries displayed multiple gains; in one of those, two additional losses were observed. Multiple gains were detected in two of the four first recurrences, but none in the two second recurrences. Across all 22 samples, gains occurred in more than one sample on chromosomes arms 1p, 9q, 10q, 12q, 16p, 16q, 17q, 19p, 19q, 20q, and 22q. Losses were found in a single case exclusively on chromosome 4. Sex chromosomes were frequently affected in both primary tumors and recurrences. There was no correlation among tumor staging, age, and DNA amplification. No DNA aneuploidy was detected, a finding in accordance with the generally benign characteristics of JNAs. Our observations suggest that in JNA the activation of oncogenes is more likely than the inactivation of tumor suppressor genes. Autosomal gains in the primary tumor should be further evaluated as markers for a potentially increased risk of recurrence after surgical removal in this entity.

Impact of vascular endothelial growth factor release on radiation resistance.

There is increasing evidence of an angiogenic response of irradiated tumors resulting in decreased radiation sensitivity. However, little is known about the contribution of tumor vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF)-release induced by irradiation to the individual level of resistance. In this in vitro study, we analysed the VEGF- and bFGF-release of six epithelial tumor cell lines before and after irradiation and correlated these data to the corresponding irradiation resistance. Two head and neck squamous cell carcinoma (HNSCC), two renal cell carcinoma (RCC), and two ovarian cancer (OC) cell lines were each exposed to 2 or 6 Gy single dose using a 137Cs-source. Non-irradiated controls were processed in parallel. Survival rates were assessed by colony assays as a measure of resistance. The released VEGF and bFGF was quantified by ELISA assays. Additionally, the expression of VEGF and its respective receptors (FLK, FLT, and NRP1) was visualized by immunohistochemistry. VEGF-release was significantly increased (p<0.05) in all cell lines after irradiation. Release was most prominent in the RCC cell lines, less in the HNSCC cell lines and lowest in the OC cell lines. Radiation resistance correlated to the absolute level of released VEGF after irradiation as well as to its relative increase (r>0.9, p<0.01). bFGF levels were not correlated to resistance. VEGF and all three VEGF-receptors were detected in all cell lines analyzed supporting the concept of an autocrine protective mechanism. We suggest that tumor cell survival after irradiation may be enhanced by released VEGF and that the level of released VEGF directly corresponds to the resistance of the tumor to irradiation.

mRNA-induction and cytokine release during in vitro exposure of human nasal respiratory epithelia to methyl methacrylate.

BACKGROUND: Methyl methacrylate (MMA) has been reported to cause histopathological changes in rodent nasal epithelium after inhalation challenges. Data in humans are lacking. METHODS: In this in vitro design 22 primary cell cultures taken from inferior turbinate tissue of healthy individuals were exposed to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression and cytokine release of inflammatory mediators were quantified after 4h and after 24h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were performed from culture supernatants for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1 and GMCSF. RESULTS: Acute inductions of mRNA after 4h were observed for TNF-alpha, IL-1beta, IL-6, IL-8 and MCP-1 at 50 ppm. ELISA analysis of the described parameters did not reveal any significant upregulations at both concentrations after both 4h and 24h. CONCLUSIONS: The obtained data suggest that exposure of human respiratory epithelia in vitro to 50 ppm and to 200 ppm of MMA does not induce lasting upregulation of the inflammatory mediators measured in this study. The exposure limit of 50 ppm appears safe following these results obtained from human respiratory epithelia.

Forty-one cases of congenital choanal atresia over 26 years--retrospective analysis of outcome and technique.

This retrospective analysis reflects the outcome of various techniques used in a series of 41 cases of choanal atresia treated at the Department of Otoloaryngology, Head- and Neck Surgery at the University of Mainz between 1980 and 2006. Thirteen bilateral and 28 unilateral cases are included. After endonasal management in 38 and a transpalatine approach in 3 cases a total of 15 patients needed revision surgery between 1 and 5 times to establish a stable result. Postoperative stenting was used in 23 patients with a failure rate of 35%, whereas only 11% of the 18 patients without stenting had to be revised. None of those 5 cases where Mitomycin C had been applied intraoperatively in combination with postoperative transnasal dilations needed surgical revision. We conclude that the endonasal micro-endoscopic surgical approach is successful if combined with postoperative dilations for up to one year. Stenting should be abandoned as it stimulates granulation formation that frequently leads to restenosis. The intraoperative application of Mitomycin C offers a promising adjunct in achieving a stable

Technical Note: First Use of Endonasal Confocal Laser Endomicroscopy - Feasibility and Proof of Concept

Abstract Introduction Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional realtime analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses.