Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

[Disinfection and recontamination of rigid endoscopes: improved safety using an immersion quiver system]. / Desinfektion und Rekontamination starrer Endoskope: Mehr Sicherheit durch ein Tauchköchersystem.

BACKGROUND: In Otorhinolaryngology, rigid endoscopes are used daily at a high frequency. There is no consensus for reprocessing these medical instruments. Often immersion disinfection procedures are used. The present study examined the possible risk of recontamination by this disinfection method and investigated the possibility of avoiding this risk by using a new immersion quiver system. METHODS: Using coloured markers, a possible contact of the endoscope with the top edges of quivers of different diameters during endoscope removal was tested for. In addition, it was evaluated whether Staphylococcus aureus transfer is possible via this route. The same methodology was applied to a new immersion quiver system. RESULTS: Whenever removing the rigid endoscopes from the conventional quiver, these touched the top of the quiver, regardless of its diameter. A transfer of Staphylococcus aureus from the quiver to the endoscope via this route could be detected in five out of eight attempts. During endoscope removal from the new immersion quiver system, no contact of the endoscope with the outer quiver occurred in 20 passes. In none of eight trials was a transfer of Staphylococcus aureus from previously contaminated immersion quivers to the endoscope shown; all immersion quivers were sterile after disinfection. DISCUSSION: After conventional immersion disinfection, recontamination of rigid endoscopes by a contaminated quiver edge is possible. An immersion quiver system can resolve this risk of recontamination easily, by decontaminating not only the endoscope, but also the immersion quiver (inner quiver) itself in the disinfectant solution.

[NiTiBOND an optimized self-crimping stapes prosthesis for treatment of otosclerosis]. / NiTiBOND, eine optimierte Steigbügelprothese zur chirurgischen Behandlung der Otosklerose.

BACKGROUND: Compared to traditional stapes prostheses, self-crimping prostheses have been shown to result in similar, if not better, closure of the air bone gap in patients undergoing stapedotomy for otosclerosis. To achieve self-crimping, nitinol, a shape memory alloy, has been used for several years but concerns have been raised regarding possible damage to the incus and its muco-periosteum. We investigate these concerns with regard to the newer NiTiBOND stapes prosthesis in an observational multi-centre study. MATERIAL AND METHODS: In a multicentre, prospective observational study, 76 patients undergoing stapedotomy with the NiTiBond prosthesis across 4 centres were compared to 75 -retrospectively selected control SMart patients. Complications, intra-operative user-friendliness and audiological results at 3 months were documented. RESULTS: Audiological improvement and the rate of complications were similar in both groups. Non inferiority was shown at all frequencies and in the pure-tone average. The NiTiBOND prosthesis was described as very user-friendly. CONCLUSIONS: By eliminating manual crimping, stapedotomy using the NiTiBOND prosthesis can be facilitated and standardized. Furthermore, intraoperative handling characteristics of the prosthesis are very good which may further reduce operative risk. Importantly, we show that these benefits are not to the detriment of audiological outcome. Larger and longer-term studies are required to further evaluate results.

[Glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma]. / Glossopharyngeusneuralgie nach Resektion eines Glossopharyngeusschwannoms.

Glossopharyngeal neuralgia is a rare condition and the origin is mostly idiopathic. Causes of symptomatic glossopharyngeal neuralgia can be tumors, infarction or trauma. We report the case of a 28-year-old patient who developed glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma, which is an extremely rare tumor. Treatment consisted of orally administered pregabalin and a series of injections of buprenorphine in the superior cervical ganglion (ganglionic local opioid application/analgesia, GLOA) which led to a substantial decrease in the frequency of pain attacks. This improvement was maintained at 1-year follow-up. This is the first report of development of glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma.

[Tumour of the endolymphatic sac in a 12-year-old child]. / Tumor des Saccus endolymphaticus bei einem 12-jährigen Kind.

We present the case of a 12-year-old boy with right-sided pantonal sensorineural hearing loss. With the help of imaging diagnostics a tumour of the right temporal bone was detected. It was resected using a transmastoid approach. Histopathological study showed a low-grade adenocarcinoma of the endolymphatic sac, known as Heffner tumour. An association with the von-Hippel-Lindau complex - as often reported in the medical literature - could not be proven.

[Superior semicircular canal dehiscence syndrome: a case of Tullio phenomenon]. / Syndrom des dehiszenten superioren Bogengangs: Tullio-Phänomen aufgeklärt.

Superior semicircular canal dehiscence syndrome is a clinical picture with sound and pressure-induced vertigo, autophony, hearing loss and a lowered bone conduction threshold. It is an important differential diagnosis to otosclerosis and patent eustachian tube. Diagnostic investigations include audiometric testing, nystagmus provocation, computed tomography and vestibular evoked myogenic potentials. Surgical repair of the dehiscence represents a curative therapeutic option. We describe the disease symptoms on the basis of a typical case.

[Verification of malleus head fixation : computed tomography as diagnosis standard]. / Verifikation der Hammerkopffixation : Computertomographie als Diagnosestandard.

Malleus head fixation and otosclerosis causing conductive hearing loss are often difficult to differentiate by clinical features. Up to now exploratory anterior tympanotomy was necessary to distinguish these pathologies. The case of a 22-year-old male suffering from conductive hearing loss of the right ear is presented. Otosclerosis was suspected and high-resolution CT scanning of the petrous bone was performed. The diagnosis was confirmed radiologically by the detection of an isolated malleus head fixation. Instead of explorative anterior tympanotomy, radiological and audiological controls were combined for the follow-up.

[Otorhinolaryngologic disorders associated with diving]. / Otorhinolaryngologische Erkrankungen beim Tauchen.

The number of Germans practicing sea diving has grown, so doctors are increasingly confronted with questions pertaining to diving. They concern not only patient fitness but also prevention and therapy of associated disorders and disease. This article describes predisposing factors and otologic, rhinologic, and laryngologic problems associated with diving. The most common medical problem is inflammation of the external auditory canal; the most common -Barotrauma is to the middle ear. Case studies are used to demonstrate these and other disorders associated with diving.

[Endolymph homeostasis and Menière's disease: fundamentals, pathological changes, aminoglycosides]. / Endolymph-Homöostase und M. Menière : Grundlagen, pathologische Veränderungen, Aminoglykoside.

Although low dose intratympanal gentamicin has empirically been very effective in treating Menière's disease, the mechanisms of elimination or amelioration of vertigo are still insufficiently understood. Most animal studies investigating the effect of aminoglycosides used high doses that damage or kill hair cells and many other cell types of the inner ear. Additional studies are needed to investigate the effects of low dose gentamicin to elucidate the mechanisms affecting vertigo. In this article it will be explained how disturbances of endolymph homeostasis lead to endolymphatic hydrops and finally to leakage of K(+) from the endolymph into the perilymphatic space. This can lead to a non-physiological activation of vestibular nerve fibres thus causing vertigo.

[The model project "newborn auditory screening" in the Upper Palatinate: high process and result quality of an interdisciplinary concept]. / Modellprojekt Neugeborenen-Hörscreening in der Oberpfalz: Hohe Prozess- und Ergebnisqualität durch interdisziplinäres Konzept.

BACKGROUND: In May 2003, a newborn auditory screening program was initiated in the Upper Palatinate. METHODS: Sequential OAE- and BERA-screening was conducted in all hospitals with obstetric facilities. The Screening Center at the Public Health Authority was responsible for the coordination of the screening process, completeness of participation, the follow-up of all subjects with a positive screening test and the quality of instrumental screening. RESULTS: A total of 96% of 17,469 newborns were screened. The referral rate at discharge was 1.6% (0.4% for bilateral positive findings). For 97% of the positive screening results, a definite diagnosis to confirm or exclude hearing loss was achieved; for 43% only after intervention by the Screening Center. Fifteen children with profound bilateral hearing impairment were identified of whom eight were only detected by the intervention of the Screening Center. CONCLUSION: The effective structures established in the Upper Palatinate provide a standard for the quality of neonatal auditory screening achievable in Germany.

Safety of gold in stapes surgery.

Gold prostheses in middle ear surgery were found to have a higher extrusion rate than prostheses made from titanium. Incidences of deafness after insertion of a gold piston into the vestibule during stapes surgery have been observed. The aim of this study was to find out to what degree gold cations can diffuse from the prosthesis piston into the perilymph. For this, gold prostheses were incubated in artificial perilymph for four months, after which the gold content of the perilymph was analysed. As gold exhibits a special behaviour in complex fluids like the perilymph, a new analysing method was developed. The results show that gold does leak out of the pistons, that it can be reliably measured and that the amount of gold reaching the perilymph depends on the contact area. As the amount of gold measured in the perilymph stays far below the toxic level, it is very unlikely that the gold cations diffusing from a stapes prosthesis into the perilymph have a toxic effect on the inner ear hair cells. Inflammatory or allergic reactions to gold induced by direct tissue contact, however, cannot be excluded.

Domestication differentially affects cochlear nucleus subdivisions in the gerbil.

We analyzed the effects of domestication on the subdivisions of the cochlear nucleus in the gerbil (Meriones unguiculatus) by comparing their volumes and rostrocaudal extents in laboratory gerbils and in age-matched F1 offspring of gerbils caught in the wild. In addition, soma size was systematically analyzed in the anteroventral cochlear nucleus of both groups. Total cochlear nucleus volume and rostrocaudal extent were not significantly different between groups either for young (postnatal day 9) animals before the onset of hearing or for young 4-month-old animals. However, the dorsal cochlear nucleus was significantly larger and the anteroventral cochlear nucleus was significantly smaller in young adults of the wild strain. Thus the relative proportions of the cochlear nucleus subdivisions differed between the groups. In addition, soma size was significantly larger in the low-frequency portion of the anterovental cochlear nucleus in domesticated gerbils compared to wild gerbils. To our knowledge, this is the first reported instance of a well-defined brain structure (e.g., the antreovental cochlear nucleus) being larger in the domesticated than in the wild form.

The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.

The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.

Sound induced expression of c-Fos in GABA positive neurones of the gerbil cochlear nucleus.

To characterize c-Fos-expressing neurones in more detail, a double labelling technique was developed to simultaneously demonstrate the presence of GABA-like and c-Fos-like immunoreactivity in cryostat sections of the gerbil cochlear nucleus. The animals were exposed to a wide-band noise stimulus for the induction of c-Fos expression. The distribution of c-Fos-positive cells and GABA-positive somata was consistent with previous reports. Our double labelling approach revealed the presence of GABA-positive cells that showed c-Fos expression after noise stimulation. One interpretation of this finding is that a prolonged acoustic exposure induces long term changes in inhibitory interneurones to adjust the output of the cochlear nucleus.

The origin of efferent fibers to the inner ear in a turtle (Terrapene ornata). A horseradish peroxidase study.

The origin of efferent acoustic and vestibular fibers was determined in the turtle Terrapene ornata. After injection of an aqueous solution of horseradish peroxidase (HRP) into either the cochlear duct or into the ampullae of the horizontal and anterior semicircular canals, neurons in the medullary reticular formation were labeled by the reaction production of retrogradely transported HRP. These neurons were located bilaterally in the medial reticular nucleus. The majority were found ipsilateral to the injection site. There was no demonstrable difference in size, shape, and labeling pattern between efferent acoustic and efferent vestibular neurons. The crossed component component of efferent acoustic fibers, however, was rather sparsely developed.

Efferent acoustic neurons within the lateral superior olivary nucleus of the guinea pig.

The cells of origin of the olivocochlear bundles in the guinea pig were labeled by retrograde axonal transport with either the fluorescent dye 'Fast Blue' or horseradish peroxidase (HRP). Labeled cells were found bilaterally in the superior olivary complex, as described previously. Moreover, an extremely large population of labeled cells occurred within the cell mass of the lateral superior olivary nucleus (LSO) ipsilaterally to the injection site. Preliminary electron microscopical observations confirmed that the labeled LSO cells were distinctly smaller than the unlabeled LSO cells. The labeled cells contained a large nucleus that exhibited extensive invaginations.

Origin of centrifugal fibers to the labyrinth in the frog (Rana esculenta). A study with the fluorescent retrograde neuronal tracer 'Fast blue'.

After injecting a solution of a fluorescent retrograde neuronal tracer (Fast blue, Diamidino compound 253/50) into the perilymphatic space of the frog labyrinth (Rana esculenta), labeled cells were found in the ventral and dorsal nuclei of the VIIIth nerve and in the nucleus reticularis medius. We consider these labeled cells to be the origin of the efferent innervation of the frog labyrinth. No evidence was found for the existence of a direct cerebello-labyrinthine connection.

The origin of centrifugal fibers to the inner ear in Caiman crocodilus. A horseradish peroxidase study.

The origin of acoustic and vestibular efferent fibers was investigated in Caiman crocodilus. After injection of horseradish peroxidase (HRP) into the cochlear duct or into the ampullae of the horizontal and anterior semi-circular canals, cells in the medulla oblongata exhibited retrogradely transported HRP reaction product. Efferent vestibular fibers were found in the medial reticular nucleus, at the level of the oliva superior. There were more labeled neurons ipsilateral to the injection site. Efferent acoustic neurons were found close to or inside the rostroventral division of the oliva superior. They spread out into the medial reticular nucleus bilaterally, More labeled efferent acoustic neurons occurred contralateral to the injection site.