Schleimhautveränderungen im Kehlkopf

Background

Optical coherence tomography (OCT) and high-frequency ultrasound are promising new methods in the early diagnosis of laryngeal cancer. However, no reliable values are given in the literature for epithelial thickness in early laryngeal cancer and its precursor lesions of the vocal folds.

Patients and methods

In the present study, epithelial thickness in different benign and malignant lesions of the vocal folds was determined histologically using a normal white light microscope.

Results

The vocal fold mucosa showed progressive thickening over the different grades of dysplasia up to microinvasive carcinoma, while additional inflammation did not have any significant influence on the total epithelial thickness. In moderate dysplasia, however, the mean thickness of the epithelium was found to be double that of normal mucosa, and in severe dysplasia and carcinoma in situ, as much as three times that of normal mucosa. In the presence of microinvasive carcinoma, the average thickness of the epithelium was found to be as much as six times that in healthy mucosa. On the other hand, in case of benign lesions such as Reinke’s edema, polyps, chronic laryngitis, and papillomas there was only slight epithelial thickening.

Conclusions

Determination of epithelial thickness by OCT or high-frequency ultrasound may allow conclusions on whether or not a laryngeal lesion is malignant.     

Zellen der Tumorfront

Background

With a frequency of about 90?%, head and neck squamous cell carcinomas (HNSCCs) are the most common malignancies of the upper aerodigestive tract. The cancer stem cell (CSC) hypothesis postulates that CSCs are the dangerous part of the tumor and are relevant to metastasis, invasiveness and resistance to chemotherapy.

Methods

Tissue samples taken from HNSCCs and normal mucosa were tested for the expression of several established CSC markers. The expression and activity of the matrix metalloproteinase MMP-9 was also investigated.

Results

Cells of the invasive tumor front expressed the basal stem cell markers CD44, ALDH1 and CK14. However, in contrast to the noninvasive basal cell layer of normal mucosa, HNSCC samples were also positive for active MMP-9, which lends the tumor its gelatinolytic activity.

Conclusion

These observations suggest a model in which cells of the invasive front are derived from the basal cell layer of normal mucosa and harbour the CSCs. Future studies should thus focus on the cells of the invasive front in particular, since the activity of these cells may form the basis for tumor recurrence and therapy resistance.     

Trägt Nikotin zur Krebsentstehung im oberen Aerodigestivtrakt bei?

Background

It is accepted that nicotine in tobacco smoke causes addiction via nicotinic acetylcholine receptors in the central nervous system. For a long time, the tumorigenic potential of smoking was attributed to compounds other than nicotine. However, more recently data have accumulated which suggest that nicotine may add to the cancer risk by stimulating cellular growth via non-neuronal acetylcholine receptors, by suppressing apoptosis, and by inducing angiogenesis not only in atheromatous plaques but also in tumors. In the present study the possible direct genotoxic effects of nicotine on DNA were investigated in human target cells of carcinogenesis in the upper aerodigestive tract.

Patients and methods

Human nasal mucosa, lymphatic tissue of the palatine tonsils, supraglottic epithelium of the larynx, and peripheral lymphocytes were exposed to rising concentrations of nicotine. DNA damage was investigated by alkaline single-cell microgel electrophoresis (Comet) assay. Cytotoxicity was assessed by trypan blue exclusion.

Results

Nicotine induced dose-dependent DNA damage in all cell types at low cytotoxic concentrations that allowed viabilities well above 80%. The lowest nicotine concentrations eliciting a significant increase in DNA migration were 1 mM for tonsillar cells and 0.25 mM for all other cell types.

Conclusion

Nicotine induces genotoxic effects in human target cells of carcinogenesis in the upper aerodigestive tract at relevant concentrations. Thus, nicotine may contribute directly to tumor initiation resulting from smoking.     

Grundlagenuntersuchungen für Stimmlippendynamik

Background

The understanding of normal and pathological vocal fold dynamics is the basis for a pathophysiological motivated voice therapy. Crucial vocal fold dynamics concerning voice production occur at the medial part of the vocal fold which is seen as the most critical region of mucosal wave propagation. Due to the limited size of the larynx the possibilities of laryngeal imaging by endoscopic techniques are limited.

Material and methods

This work describes an experimental set-up that enables quantification of the entire medial and superior vocal fold surface using excised human and in vivo canine larynges.

Results

The data obtained enable analysis of vocal fold deflections, velocities, and mucosal wave propagation. The reciprocal dependencies can be examined and different areas of vocal fold dynamics located. The vertical components obscured in clinical endoscopy can be visualized. This is not negligible.

Conclusions

In particular it is shown that the vertical deflection, which cannot be observed by clinical examination, plays an important part in the dynamics and therefore cannot be omitted for therapeutic procedures. The theoretically assumed entrainment and influence of the two main vibration modes enabling normal phonation is confirmed.     

Chronische Laryngitis und Tumorerkrankung unter dem Einfluss von hormonell wirksamen Substanzen

Backround

In the literature the potential effect of sexual steroids on the development and growth of laryngeal carcinomas, and even other tumor entities of the upper aerodigestive tract, within the context of multifactorial carcinogenesis has been the subject of controversial discussion. Experimental cell studies have provided evidence for the differentiated effects of these agents. Apart from the male preponderance in tumor formation, the high incidence at an age characterized by decreased peripheral androgenic signalling should be noted.

Patients and methods

Two patients with chronic symptoms and abnormal hormone levels are reported who underwent a hormonal trial regimen. The course of their disease was followed up for a period of more than 10 years.

Results

In the first case of a patient suffering from chronic hyperplastic laryngitis for 17 years, a close correlation was found between the treatment with the 5α-reductase inhibitor Finasteride, the drop in serum levels of dihydrotestosterone (DHT), and the appearance of an invasive squamous cell carcinoma of the vocal cord. During the postoperative 7-year follow-up without recurrence the androgen serum levels were within normal range. The laryngeal mucosa did not display any further dysplastic changes. Retrospective studies of the biopsies demonstrated a significant degree of epidermal growth factor receptor (EGFR) expression, the characteristic high degree of EGFR activity in all of the tumor tissue, and a significantly lower degree of activity in the subsequent excision biopsies. In the second patient, who had undergone previous surgery for mesopharyngeal cancer at another site before the present tumor operation, rapid recurrence was seen within 2 years. Despite radical revision surgery and subsequent irradiation the patient insisted on carrying on with his work. He complained about a general lack of stamina and libido. His androgen serum levels were at the low-end of the normal range and even below that. The daily administration of 25 mg dehydroepiandrosterone (DHEA) resulted in normal androgen serum levels and improved his wellbeing. He has been free of recurrence for 10 years.

Discussion

Occasional long-term follow-up of patients supports the circumstantial evidence of previous experimental cellular studies that a dysbalanced androgen metabolism appears to act as cofactor in the genesis and development of malignant tumors of the upper aerodigestive tract.     

Therapeutische Beeinflussung von Schwingungsirregularitäten durch Elektrostimulationstherapie

Background

Vocal fold vibration may be adversely affected by numerous conditions. We studied whether electrical stimulation can alleviate vocal fold vibration irregularity.

Methods

A total of 90 patients with varying degrees of vocal fold vibration irregularity due to unilateral vocal fold paresis were recruited and received either electrical stimulation therapy or a voice exercise/behavioral treatment. Vocal fold vibration irregularity was calculated from a speech sample before and after therapy.

Results

After 3 months, the increase in vibration stability was significantly greater for patients who received electrical stimulation therapy compared with patients who received traditional voice therapy.

Discussion

Voice control includes vocal fold vibration regularity. It appears that electrical stimulation therapy can be used effectively in patients with vocal fold paresis and concomitant loss of voice control.     

Reproduzierbarkeit und Reliabilität des Phonovibrogramms

Background

Phonovibrography is capable of visualizing vocal fold vibrations in a static two-dimensional image, the so-called phonovibrogram (PVG). It allows quantification of the entire vocal fold vibration patterns. In this study we investigated the accuracy and reproducibility of PVG measures by analyzing high-speed laryngoscopy videos of healthy vocal fold vibrations.

Methods

High-speed laryngoscopy videos of 12 female speech therapists and 12 vocalists from the Regensburg Cathedral choir were analyzed. For evaluation purposes, PVG analysis was performed for two different sections of each video.

Results

The mean difference between the high-speed sections was 1.6°±0.5° for the female and 2.3°±0.6° for the male subjects. Within the sections, the mean variance of the PVG parameters was 3.5°±0.7° (therapists) and 3.7°±1.0° (vocalists). Likewise, a high left/right accordance of the PVG parameters, 5.3°±0.5° for therapists and 5.9°±1.9° for vocalists, was obtained.

Conclusion

Vibrational patterns of normal vocal fold vibrations were very precisely quantified by the introduced PVG parameters. The high accuracy and reproducibility of PVG analysis provides a basis for prospective clinical trials dealing with precise characterization of pathological vibration patterns.     

Lokale und regionäre Rezidive von laserchirurgisch behandelten Plattenepithelkarzinomen des oberen Aerodigestivtrakts

Introduction

The aim of the present study is to identify clinical factors that influence the incidence and the prognosis of local and regional recurrences.

Patients and methods

The data of 1,426 patients with newly diagnosed squamous cell carcinoma of the upper aerodigestive tract who were treated by curative laser microsurgery between August 1986 and December 2002 were reviewed.

Results

In 381 patients (27%), tumor recurrences were detected during follow-up. The frequency of local as well as regional recurrences significantly correlated with the initial stage of tumors. Recurrences of advanced carcinomas occurred considerably sooner than those of stage II and I cancer. During the 4th year of follow-up, patients with early stage disease had a recurrence rate twice as high as those with advanced carcinomas. Survival with recurrence was adversely affected by adjuvant radiotherapy as part of initial treatment, simultaneous local and regional manifestation of recurrence, male sex, advanced stage of initial disease, and by oral or hypopharyngeal site of the primary tumor.

Conclusion

Early carcinomas of the upper aerodigestive tract recur at a lower rate than advanced stage diseases, but after a longer mean latency period. As a consequence, these patients should receive close follow-up also during the 3rd and 4th years after treatment, particularly as the prognosis of their recurrences is most often favorable.     

Pr?valenz auff?lliger Schleimhautbefunde bei Patienten in HNO-Praxen

Objective

To date, no secondary prevention program is in place for patients carrying an increased risk for developing head and neck cancer (HNSCC). In terms of successful, long-term curative therapy and increased quality of life, it would be useful to detect such diseases at an early stage.

Patients and Methods

A total of 370?patients with at least one risk factor such as ??smoking??, ??alcohol??, or ??reflux disease?? and without any symptoms were examined during a 1-year period using standard HNO methods (e.?g. endoscopy) for suspicious alterations of the mucosa of the upper aerodigestive tract.

Results

In 13 (3.5%) of all 370 cases a biopsy was taken for further diagnosis. Squamous cell carcinoma was found in eight cases, while one further patient was suffering from non-Hodgkin lymphoma.

Conclusions

It is simple and safe to examine patients at risk of developing HNSCC by standard HNO methods. The rate of detected carcinomas is much higher than in former investigations, likely because our survey focused only on patients with specific risk factors.     

Anatomic factors affecting the use of ultrasound to predict vocal fold motion: A pilot study

Purpose

Ultrasonography is a well-established modality for visualization of head and neck anatomy. Using ultrasound to detect vocal fold mobility has been described before, but no study has evaluated factors affecting the exam reliability. The aim of the study is to determine anatomic factors influencing the reliability of ultrasound to detect vocal fold motion.Methods and materialsPatients underwent ultrasound evaluation and flexible laryngoscopy to assess vocal fold motion from August 2015 to March 2016. Length, accuracy, and clarity of ultrasound examination were assessed, compared to flexible laryngoscopy. For patients with prior neck CT scan imaging, laryngeal anatomy was independently assessed by a blinded neuroradiologist.

Endoskopie des Larynx mit Hyperspectral Imaging

Background

Hyperspectral imaging has been proven to be useful in remote earth sensing, e.g., satellite-based classification of vegetation. After modifying it for in vivo evaluation of the larynx using microscopy, we show its adoption for endoscopes.

Materials and methods

In addition to routine microlaryngoscopies under white light inspection, the laryngoscopy was also performed with not only a conventional operation microscope mounted with a tuneable monochromatic light source and a synchronously triggered monochromatic CCD camera (n?=?47 patients), but also a similarly modified rigid 0° endoscope (n?=?16 patients). Hyperspectral image cubes were obtained between 390 and 680?nm, analyzed using established software tools, and the data using microscope versus endoscope were compared.

Results

Under endoscopy, illumination was more even and sterical resolution appeared unchanged at significantly shorter image acquisition times. Hyperspectral classification delineated areas of altered mucosa without further external information irrespective of whether image cubes were generated with microscopy or endoscopy.

Conclusion

Hyperspectral imaging can be transferred not only to micro(laryngo)scopy but also to endoscopy with rigid optics. This opens the way to a variety of clinically relevant anatomical regions (e.g., upper aerodigestive tract). Its adoption to flexible optics will further broaden this spectrum.     

Langzeitergebnisse nach mikrolaryngoskopischer Abtragung von Reinke-Ödemen

Background

In the case of Reinke’s edema, the usual aim of microlaryngoscopic vocal fold stripping is an improvement of voice quality. Long-term results concerning functional voice quality in the literature vary widely. Whether and to what degree surgical intervention leads to the desired postoperative results is therefore still an open question. Therefore we conducted a follow-up study to review our own treatment results.

Materials and methods

We questioned 88 patients treated for Reinke’s edema, either orally or by means of a written questionnaire, 6 months to 7 years (mean: 3.5 years) after the operation (longitudinal incision, removal of the edema by suction, resection of surplus vocal cord mucosa), asking about postoperative voice quality and subjective impression of how successful the operation had been. In all 63 patients answered the questionnaire; 16 agreed to undergo follow-up laryngostroboscopy.

Results

51 patients (81%) reported a postoperative improvement in voice quality, 8 patients (13%) rated their voice quality as unchanged, and 4 patients (6%) complained of deterioration in their voice quality. Among the patients whose voices were subject to professional strain (n=27) a lower proportion experienced successful results (voice quality improved: 71%; unchanged: 21%; worse: 8%) than among patients without vocal strain (n=36; improved: 86%; unchanged: 11%; worse: 3%). Postoperative elimination or restriction of such etiological factors as smoking and vocal strain also improved the long-term results. Follow-up examination in 16 patients revealed a good correlation between the patients’ subjective reports and the stroboscopic and auditory findings.

Conclusion

Patients should be selected very carefully for surgical treatment of Reinke’s edema. The elimination of etiological factors is of highly significant in terms of the prognosis. Before surgery patients should be fully informed of how uncertain the prognosis is.     

Is voice therapy effective for the treatment of dysphonic patients with benign vocal fold lesions?

Objective

To update our knowledge regarding the effectiveness of voice therapy for the treatment of vocal disturbance associated with benign vocal fold lesions, including vocal polyps, nodules and cysts, and for determining the utility of voice therapy in treating organic voice disorders, while highlighting problems for the future development of this clinical field.

Value of ultrasonography in diagnosis of pediatric vocal fold paralysis

Objectives

To investigate the appearance of the pediatric larynx on ultrasound images and the diagnostic potential of ultrasound in cases of pediatric vocal fold paralysis.

Methods

First, we confirmed the ultrasonographic features of the laryngeal landmarks in 2 pediatric cadaveric larynxes. Secondly, 45 children were enrolled in a clinical study (13 patients with vocal fold paralysis and 32 normal children). Quantitative analysis of vocal fold mobility was carried out by measuring the maximum glottic angle (MGA) and vocal fold-arytenoid angle (VAA).

Results

All the paralyzed vocal folds showed abnormal mobility, and were flaccid during breathing and phonation. The rima glottis appeared as a hyperechoic air-column band in ultrasound images during phonation. The mean value of the MGA was 61.47 ± 9.00 in the normal larynx and 42.25 ± 10.41 in the paralyzed larynx. In the affected side of the paralyzed larynx, the VAA in maximum abduction was smaller than that in the normal larynx or in the unaffected side. The median difference of the VAA between maximum abduction and maximum adduction was less than that in the normal larynx. The kappa value was 0.96.

Conclusion

MGA and VAA are quantitative indicators of vocal fold immobility. Ultrasound is a reliable method of diagnosis of pediatric VFP. To diagnose VFP from an ultrasound image, the criteria are: (1) abnormal mobility (this was the most important and direct evidence), (2) hyperechoic air-column band of the glottic rima during phonation, (3) flaccid vocal fold and (4) asymmetry of the glottal structures.     

Plattenepithelkarzinome im Kopf-Hals-Bereich

Introduction

Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin or mucous membranes. After the injection of a photosensitiser, the tumour area is exposed to non-thermal laser light. This causes a phototoxic reaction, producing oxygen radicals that destroy the tumour cells.

Patients and methods

From November 2004 to February 2006, a total of 24 patients with recurrent or secondary tumours after squamous cell carcinoma of the head and neck were treated with PDT at the German Armed Forces Hospital in Ulm after other treatment options had failed. Meta-tetrahydroxyphenyl chlorin (mTHPC), known under the trade name of Foscan, was used as the photosensitising agent.

Results

Complete remission was observed in 12 patients (50%) and partial remission was seen in nine (37.5%). Three patients did not respond to treatment. The mean duration of overall survival was 305.7 days (±199.4) after completion of treatment. The mean duration of recurrence-free survival was 302.7 days (±144.9) for patients with complete remission. There were no serious complications.

Conclusions

Photodynamic therapy is an important treatment option for patients who develop recurrent or secondary tumours after squamous cell carcinoma of the upper aerodigestive tract and fail to respond to other treatments. In addition, PDT may play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx in the future.     

Phonovibrogramm: Stimmlippendynamik in einem Bild

Background

Stroboscopy is widely used and is quite adequate for the examination of normal voices, but with increasing hoarseness its suitability declines, even when it is supplemented by video recordings and image evaluation. Real-time procedures such as videokymography or high-speed (HS) video imaging are more suitable methods of observing the movements of the vocal folds in such cases. A drawback of any video recording is the later time-consuming offline replay of the films in slow motion and our restricted pattern recognition for motion and other time-dependent processes.

Methods

The phonovibrogram (PVG) is an image-processing algorithm that extracts the vocal fold motions of a whole laryngoscopic HS video film and automatically compresses them into a single image.

Results

Simple patterns that vary from person to person are revealed by PVG; these can be categorized by means of simple geometric forms, which a human observer can more easily recognize and interpret than dynamic motion patterns. The PVG computation is described in detail and an extensive guide to interpretation is given, illustrated by reference to theoretical and real examples.

Conclusion

In clinical conditions, HS laryngoscopic video recording is useful only in association with automatic image processing. The PVG procedure is a promising approach and tests should be performed with a view to further clinical validation.     

Clinical impact of iodine staining for diagnosis of carcinoma in situ in the floor of mouth, and decision of adequate surgical margin

Objective

The use of iodine staining has been recommended for the early detection of squamous cell carcinoma (SCC) in the upper aerodigestive tract. The purpose was to verify the effectiveness of iodine staining in detecting early squamous cell carcinoma in the floor of mouth.

Methods

Between 1995 and 2005, otolaryngological examinations including the floor of mouth were performed for 2278 esophageal cancer patients as a screening program of high-risk patient group. Iodine staining was applied to a lightly reddish and/or white patch, and/or uneven lesions in the floor of the mouth. Forceps biopsy was performed for demarcated unstained or lightly stained lesions. Three patients with the tumors in the floor of mouth, which were diagnosed as more over T2 level just by visual examination, were excluded from this study. If SCC was found in the specimen, mucosal resection was performed with a safety margin of 2 mm from the unstained or lightly stained lesion. The incidence, rate of carcinoma in situ, and prognosis of cancer of the floor of mouth (CFOM) were assessed.

Results

Iodine staining was performed for 72 of 2278 patients (3.2%) according to the presence of suspicious reddish and/or whitish and/or uneven lesions. Of these, unstained or lightly stained areas after iodine staining were recognized in 47 patients and SCC was revealed in 28 of 47 patients. The diagnosis of other 19 patients included inflammatory mucosa (n = 11), low grade dysplasia (n = 6), and hyperkeratosis (n = 2). Sensitivity and specificity of iodine staining for detecting SCC were 100% and 59.6%, respectively. Pathological diagnosis of the 28 patients included squamous cell carcinoma in situ (n = 12), microinvasive squamous cell carcinoma (n = 15) disease, and focal invasive squamous cell cancer (n = 1). Twenty-four of 28 patients were treated with mucosal resection without mandible resection. The other 4 patients did not receive the treatment of CFOM due to concomitant far advanced esophageal cancer. In 24 patients undergoing mucosal resection, no patients developed local recurrence or metastasis to the cervical lymph nodes during an average of 74.2 months of follow-up period (from 7 to 156 months). The 5-year cause-specific survival of these patients was 100%.

Conclusion

The use of iodine staining as a part of otolaryngological examinations may be beneficial for the early detection of CFOM, including carcinoma in situ and micro-invasive SCC. Moreover, it would be very useful to determine an adequate surgical margin for locally mucosal resection.     

Chirurgisch unterstützte transversale Oberkieferdistraktion

Background

Surgically assisted rapid maxillary expansion (SARME) is a standardized method to treat cross bites in maxillofacial surgery. Changes to the nasal airways are assumed due to the anatomic dependence between the palate and the nasal floor.

Patients and methods

In this study 19 patients with a transverse deficit of the upper jaw underwent SARME. CT scans were performed 1 month pre- and 6 months postoperatively. Effects to the lower nasal airways, the nasal septum and the hard palate were subsequently evaluated.

Results

The mean distraction width of the upper jaws was 5.84 mm (SD 2.19) postoperatively. In addition to the dentoalveolar gain in width, a significant increase in the nasal floor was observed (p<0.001). The anterior part of the nasal floor was increased by 14.11%. An anterior-caudal tilt of the upper jaw was observed in the anterior part measuring 1.5 mm (SD 1.05). No significant deviation of the nasal septum occurred.

Conclusion

SARME has a significant effect on ear, nose and throat medicine. Nasal airways enlarge significantly, while no significant deviation of the nasal septum is observed.