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.

Effects of radiation on the expression of adhesion molecules and cytokines in a static model of human dermal microvascular endothelial cells.

BACKGROUND: Radiation-induced wound healing complications represent an important clinical problem. Microvascular compromise is an important component of its pathogenesis and the microvascular endothelial cell is the key representative affected at the cellular level. MATERIAL AND METHODS: Human dermal microvascular endothelial cells (HDMEC) were cultured and irradiated with doses of 2 to 12 Gy. Cell density was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatants of HDMEC were determined by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Non irradiated HDMEC were used as controls. RESULTS: Cell density was significantly impaired in irradiated cells compared to non irradiated controls. Radiation resulted in significant elevation of levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of HDMEC in a dose dependent manner. CONCLUSION: The inflammatory response observed clinically after radiation seems to correlate with elevated expression of cytokines and adhesion molecules by microvascula endothelial cells. The model of HDMEC documents the impairment of microcirculation. These in vitro changes may enhance our understanding of the pathomechanisms leading to radiation-induced vasculitis and associated wound healing problems.

[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.

[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.

[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.

[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.

[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.

[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.

[Diagnosis and therapy of auditory synaptopathy/neuropathy]. / Diagnostik und Therapie der auditorischen Synaptopathie/Neuropathie.

Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as "auditory neuropathy" includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements.

[Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS)]. / Neuronavigierte repetitive transkranielle Magnetstimulation (rTMS). Ein neuartiges Therapieverfahren zur Behandlung des chronischen Tinnitus.

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability. PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [18F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation. CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

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.

[Anomalies of the skull in cleidocranial dysplasia]. / Schädelanomalien bei Dysostosis cleidocranialis. Eine HNO-ärztliche und kraniofaziale Röntgenstudie.

BACKGROUND: The description of the otorhinolaryngeal and craniofacial anomalies in patients with cleidocranial dysplasia. METHODS: For this study, 26 patients with cleidocranial dysplasia were examined after their medical history had been recorded. The main focus was placed on otorhinolaryngological and orthodontic findings. RESULTS: The portion of spontaneous mutations in our patient population was 46.1%. All patients exhibited otorhinolaryngological and craniofacial anomalies. While single ENT-anomalies were expressed in 76.9%-92.3% of the patients, the craniofacial findings were distributed over 84.6%-92.3%. CONCLUSION: The expression of this rare disorder is variable and its symptomatology not always distinct. Otorhinolaryngological and craniofacial anomalies are often apparent. Appropriate treatment can significantly contribute to an improvement in the patient's quality of life. In cases of ambiguous findings, we recommend consultation with an experienced clinician as well as genetic counselling.

New split scar cheek flap in reconstruction of noma sequelae.

The use of a split-scar cheek flap is demonstrated for restoration of lining in reconstructing the oral commissure in cases of noma.

[How do metallic middle ear implants behave in the MRI?]. / Wie verhalten sich metallhaltige Mittelohrimplantate in der Kernspintomographie?

BACKGROUND: Magnetic resonance imaging (MRI) has gained in frequency and importance as a diagnostic procedure. In respect to the close anatomical relationship in the temporal bone it is necessary to know whether it is hazardous to patients with metallic middle ear implants regarding displacement and rise in temperature. For the MR image quality artefacts caused by metallic prostheses should be low. METHODS: Four different stapes prostheses made from titanium, gold, teflon/platinum and teflon/steel, a titanium total ossicular reconstruction prosthesis (TORP) and two ventilation tubes (made from titanium and gold) were tested in a 1.5 Tesla MRI machine regarding their displacement. All objects were first placed in a petri dish, then suspended from a thread and finally immersed in a dish filled with Gadolinium. Temperature changes of the implants were recorded by a pyrometer. RESULTS: None of the implants moved when they were placed in the petri dish or suspended from the thread. On the water surface the teflon/platinum and the teflon/steel pistons adjusted their direction with their axis longitudinally to the MRI scanner opening and the teflon/steel piston floated towards the MRI-machine when put close enough to the scanner opening. No rise in temperature was recorded. All implants showed as little artefacts that would still make an evaluation of the surrounding tissue possible. CONCLUSION: Patients with any of the metallic middle ear implants that were examined in this study may undergo MRI-investigations without significant adverse effects.