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.

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.

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.

[Sinugenic metastasis of bilateral renal cell carcinoma (hypernephroma)]. / Sinugene Metastasierung eines beidseitigen Nierenzellkarzinoms (Hypernephrom).

The paranasal sinuses are a rare location of metastases. The most frequent infraclavicular primary tumor is the renal cell carcinoma (hypernephroma). We report a case of a 64-old-woman with a bilateral renal cell carcinoma and metastases in the paranasal sinuses with destruction of the skull base. If symptoms such as progressive indolent periorbital swelling or intermittent epistaxis occur in adults, one should consider a metastasis of a renal cell carcinoma to the paranasal sinuses even 10 years after nephrectomy.

Comparative electron microscopic study of the surface structure of gold, Teflon, and titanium stapes prostheses.

HYPOTHESIS: The goal of this study was to compare stapes prostheses of different materials with respect to their surface structures and to discuss their suitability for their use in stapes surgery. BACKGROUND: The surface condition of a stapes prosthesis plays an important role in relation to the type of membrane that forms between the stapes piston and the bony edge of the stapedotomy opening. The quality of this membrane in thickness and mobility is one of the determinants for postoperative hearing improvement. METHODS: The surface conditions of gold, Teflon/steel, Teflon/platinum, and titanium stapes prostheses were examined with a scanning electron microscope. The loop, shaft, and end of each prosthesis were studied. RESULTS: The gold piston was the smoothest of the four pistons examined. When it was cut with a scalpel, a very smooth surface was achieved at the end area. The Teflon piston had the roughest surface. However, when it was cut, a smooth surface with a parallel arrangement of fibers resulted. Its steel loop was the smoothest, followed by gold and platinum. The titanium shaft had a scaly surface, which remained when the end of the shaft was shortened. CONCLUSION: Because a certain roughness of the piston surface is necessary for the development of a stable membrane between the piston and the edge of the stapedotomy opening, the titanium prosthesis is considered to be the most suitable for stapes surgery of the three pistons examined.

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.

[Laryngo-hypopharyngo-esophagectomy in advanced hypopharyngeal carcinoma. Is radical surgery intervention still justified today?]. / Laryngo-Hypopharyngo-Osophagektomie beim fortgeschrittenen Hypopharynxkarzinom. Ist dieser radikalchirurgische Eingriff heute noch gerechtfertigt?

Minimal invasive laser surgery with preservation of the organs is well established in the treatment of hypopharynx carcinoma. In cases of advanced tumors of the hypopharynx, which can not be managed by laser surgery, the combined radio-chemo therapy becomes the treatment of choice because of the low morbidity and the comparable results. The indication for an operative procedure, which means loss of larynx and oesophagus, is seen more and more restrictively. From 1993 to 1997 101 patients with advanced neoplasm of the hypopharynx or larynx (larynxcarcinoma T4; hypopharynx carcinoma T3-T4 with N > 2b) were treated in the Department of Otolaryngology of the University of Regensburg. 5 of these patients underwent a laryngohypopharyngoesophagectomy. Only patients with a severe dysfunction of the larynx (dyspnea, dysphagia, aspiration) were selected for this procedure. Postoperative complications were: one insufficiency of anastomosis with secondary bleeding and five pleura effusions. In all cases postoperative radiation began within six weeks after the operation. All patients were nourished orally when they were discharged from hospital. The mean follow up was 21 months. During this time none of the patients died. In one case pulmonary metastasis was found after 11 months. In another case a regional recurrence was diagnosed after 11 months and was removed by operation. No local recurrence was found at that time. This operative procedure can be done only in experienced and well trained medical centers. Furthermore excellent cooperation of the operating teams and strong regard to the selection criteria is obligatory.

The value of T2(*)-weighted MR images for the diagnosis of acoustic neuromas.

UNLABELLED: The aim of this study was to evaluate high resolution T2(*)-weighted MRI--in our case a 3D CISS sequence--for the diagnosis of acoustic neuromas. Especially to be clarified was if high-resolution T2-weighted sequences can substitute T1-weighted contrast-enhanced sequences, and in which circumstances they can give important additional information when compared with contrast-enhanced T1-weighted sequences. METHODS AND PATIENTS: The MR examinations were performed using a 1.5-Tesla unit with a circularly polarized head coil. All 20 patients (11 females, nine males, aged from 12 to 80 years) with acoustic neuromas underwent preoperative MRI with T2*-weighted 3D CISS (slice thickness, 0.7 mm; acquisition time, 8 min) and pre- and postcontrast T1-weighted 3D MP-RAGE (slice thickness, 0.9 mm; acquisition time, 8 min) sequences. The detectability of acoustic neuromas was evaluated following the consensus of three radiologists using a 3D work station (parameters: tumor presence, extent, nerve attribution). RESULTS: All tumors were detected by both contrast-enhanced 3D MP-RAGE and 3D CISS and the diameters of the lesions were equally well measured. 3D CISS was the best sequence for the attribution of a lesion to a certain nerve. Labyrinthine involvement could be better detected using 3D CISS than contrast-enhanced 3D MP-RAGE. CONCLUSION: High-resolution T2(*)-weighted MRI is a very sensitive method for tumor screening which can also detect even small meatal and labyrinthine neuromas. In the case of abnormal findings (other pathology or variations, e.g. vascular loops); however, contrast-enhanced T1-weighted MRI is necessary in order to confirm the presence of a tumor with typical enhancement.

Delayed facial palsy following uneventful middle ear surgery: a herpes simplex virus type 1 reactivation?

In rare cases, a facial palsy appears a few days after uneventful middle ear surgery. The reason for this delayed palsy is unclear. One hypothesis is that it results from a reactivation of herpes simplex virus type 1 (HSV-1) in the geniculate ganglion of the facial nerve. From 1987 to 1996, in the course of over 1,800 middle ear operations, we observed 7 ipsilateral delayed facial palsies and investigated 5 of them using immunologic and virologic methods, including the polymerase chain reaction (PCR). We could detect HSV-1 genome with the nested primer PCR in the tongue swabs of 4 of the 5 examined patients with delayed facial palsy. The immunologic changes in these palsies are also compatible with a reactivation of HSV-1. We conclude that minimal stimulation of the facial nerve during middle ear surgery could result in a reactivation of HSV-1 in the geniculate ganglion, which may in turn lead to a facial palsy.

Correlation of 3D MRI and clinical findings in the patients with sensorineural hearing loss and/or vertigo.

The aim of the study was to correlate clinical and magnetic resonance imaging (MRI) (3D CISS and MP-RANGE) findings in patients with sensorineural hearing loss (SNHL) and/or vertigo. We found a high correlation of MRI and symptoms (17 out of 18 patients, 13 out of 13, respectively) concerning detectability of tumors and acute labyrinthitis. In the case of labyrinthine fibrosis, the correlation between clinical and MRI findings was lower. In conclusion, high-resolution MRI is very suitable in patients with SNHL or vertigo caused by tumors or acute labyrinthitis.

3D MRI of the membranous labyrinth. An age related comparison of MR findings in patients with labyrinthine fibrosis and in persons without inner ear symptoms.

PURPOSE: We compared MRI of the membranous labyrinth in patients with chronic non-neoplastic inner ear disease and MR signs of labyrinthine fibrosis and controls depending on their age, in order to establish whether there were any MR differences regarding patient age groups, control age groups and between the patients and controls themselves. MATERIALS AND METHODS: Clinical ENT examinations as well as a T2* weighted 3D CISS (Constructive Interference in Steady State) sequence with a slice thickness of 0.7 mm were performed. Our collective was subdivided as follows: 0-19 years (10 controls, 3 patients with chronic non-neoplastic inner ear disease), 20-49 years (55 controls, 8 patients), 50 years and older (40 controls, 22 patients). Detectability of labyrinthine structures (e.g. cochlea, vestibule, semicircular canals) and filling defects were evaluated. RESULTS: In the 3 age-groups of the control collective no significant differences were observed in the membranous labyrinth. However differences concerning labyrinthine detectability emerged between controls and patients in both the 20-49 years and 50 years and older age groups. In the patient collective the 3 age groups showed no significant discrepancy in the mean number of lesions. CONCLUSION: Filling defects of the membranous labyrinth on 3D CISS MR images are pathological even in older persons. We would therefore recommend high resolution T2* weighted MRI in the case of suspected labyrinthine fibrosis.

MRI of inner ear and facial nerve pathology using 3D MP-RAGE and 3D CISS sequences.

The aim of this study was to evaluate 3D CISS, unenhanced 3D MP-RAGE and contrast enhanced 3D MP-RAGE for the diagnosis of neoplastic, vascular and inflammatory lesions of the cerebellopontine angle, the inner auditory canal, the labyrinth and the facial nerve 42 MR examinations were performed on a total of 38 patients (25 males, 13 females; aged 1-77 years, mean age 43 +/- 20 years) using a 1.5 T MR unit. A T2* weighted 3D CISS sequence (TR 14.65 ms, TE 21 ms, flip angle 65 degrees, voxel size 0.7 x 0.7 x 0.7 mm3) and a T1 weighted 3D MP-RAGE sequence (TR 12.5 ms, TE 5 ms, T1 300 ms, flip angle 15 degrees, voxel size 1.0 x 0.9 x 0.9 mm3) with and without contrast medium (gadolinium-DTPA, 0.1 mmol kg-1 body weight) were used. Results of contrast enhanced 3D MP-RAGE-pathological enhancement was found in the following lesions: schwannomas of the cerebellopontine angle (CPA) and the internal auditory canal (IAC), 4; schwannomas of the IAC, 7 and labyrinthine tumours, 3; posterior fossa lymphoma, 1; meatal meningioma, 1; acute labyrinthitis, 15 and neuritis of the seventh cranial nerve, 10. Results of 3D CISS-filling defects were found with the following lesions: schwannomas of the CPA, the IAC or labyrinth, 14; lymphoma, 1; meningioma, 1; labyrinthine fibrosis, 13 and scar in the IAC, 4. These results suggest that unenhanced and contrast enhanced 3D MP-RAGE and 3D CISS are complementary MR imaging modalities. T1 weighted 3D MP-RAGE is preferred to T1 weighted 2D (turbo) spin echo sequences because of the multiplanar reconstruction possibilities of 3D sequences, which are very useful in the case of the inner ear and facial nerve.

Age-dependent effects of the onset of a conductive hearing loss on the volume of the cochlear nucleus subdivisions and the expression of c-fos in the mongolian gerbil (Meriones unguiculatus).

A monaural conductive hearing loss was induced by interrupting the chain of the middle ear ossicles on the right side in gerbils of four different age groups (P12-14, P20-21, P42 and P84). The volumes of the cochlear nucleus subdivisions and the number of cells that expressed immunoreactivity for c-fos after noise stimulation were determined on the left and right side in the deprived animals, and in undeprived control animals when they reached the age of 6 months. The anteroventral cochlear nucleus on the deprived side was reduced in volume when the deprivation started before the age of 3 months. The other cochlear nucleus subdivisions showed no systematic age-dependent reductions. The expression of c-fos in the dorsal cochlear nucleus appeared more resistant to a hearing loss, with deprivation being more effective in younger animals. c-fos expression was also dramatically reduced in the ventral cochlear nucleus, regardless of age at the onset of hearing loss.