Search

Gallbladder cancer represents a rare but dismal disease. The only curative option is complete surgical resection, though patients often develop recurrent disease. In patients with advanced biliary tract cancer, the combination of cisplatin and gemcitabine showed a benefit in overall survival compared to gemcitabine alone. However, there is no standardized second-line regimen after treatment failure. We report on a young patient with early recurrence of a gallbladder cancer with cutaneous and peritoneal metastases. Upon identification of an ERBB2 gene amplification within the NCT MASTER (Molecularly Aided Stratification for Tumor Eradication Research) exome sequencing program with resulting overexpression of HER2 in the tumors cells, the patient received a targeted therapy with the HER2 antibodies pertuzumab and trastuzumab in combination with nab-paclitaxel, which led to a durable remission for more than one year. This case report underlines the potential of molecularly aided personalized targeted therapy for patients with biliary tract cancer and the need for respective clinical trials.

Der Beitrag wendet sich gegen die These, dass in Abkehr von dem Ausgangspunkt des zweiseitigen Vertrags „multipolare Arbeitsbeziehungen“ für eine juristische Betrachtungsweise gewählt werden sollen. Neue Organisationsformen der Arbeit dürfen nicht zu Nachteilen für den Arbeitnehmer führen. Die Arbeitsorganisation wird vom Arbeitgeber vorgegeben. Der Arbeitnehmer hat keinen Einfluss darauf. Die Organisationsform ist Ausdruck der strukturellen Ungleichgewichtslage zwischen Arbeitgeber und Arbeitnehmer. Aufgabe des Arbeitsrechts ist es, die Ungleichgewichtslage zu beseitigen und nicht sie als Ausgangspunkt zu nehmen und so zu akzeptieren. This article criticizes the argument that in labour law analyses, the bipolar contract should be abandoned as a starting point in favour of multipolar employment relations.. Modern employment relations in multipolar organisations could be used to evade the given legal protection of the employee. Work organisation is the prerogative of the employer and employees have no influence over it.. It is the function of labour law to secure workers’ rights in this situation on the basis of the bipolar contract and not to weaken their position by accepting new organizational forms of work.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

With the increasing use of cochlear implants (CIs), the insertion of alloplastic material into the inner ear is nowadays an established treatment for severe to profound hearing loss in children and adults. Beyond its widespread use, the biocompatibility of the CI electrode and its interaction with the neural structures of the cochlea is not yet established.To investigate the survival and growth behavior of spiral ganglion neurons on different CI materials, spiral ganglion explants from newborn rats were cultured on silicone and platinum, on a surface combination of silicone and platinum, and, finally, on a CI electrode.The results of this study indicate that the growth of spiral ganglion neurons in vitro is strongly influenced by the different materials and their arrangement, with platinum exhibiting the highest degree of biocompatibility with respect to neurite extension. Level differences in the surface structure between silicone and platinum lead to inhibition of neurite outgrowth. Furthermore, the culturing of spiral ganglion explants on a CI electrode leads to neurite sprouting toward the electrodes made of platinum.The biocompatibility of CI materials with spiral ganglion neurons was shown in this study, but it differs with different CI materials. Besides the material itself, the arrangement of the materials can affect the neurite extension.

This study was designed to assess the postoperative quality of life (QoL) of 30 patients successfully treated with a laryngectomy.QoL was evaluated with two validated questionnaires (EORTC-QLQ-C30 and EORTC-QLQ-HN35) during the regular outpatient follow-up. To analyse the long-term quality of life, we divided our collective into two groups of patients; one consisting of patients whose treatment had been completed less than five years ago and one whose therapy had been finished more than five years ago.The collective consisted of 24 men (80 %) and 6 (20 %) women with a mean age of 58.8 +/- 8.7 years. Mean follow-up was 53 months (range: 12 - 110). Most patients (n = 15, 50 %) had a tumor stadium IV after UICC. Voice rehabilitation was achieved in all patients with a Provoxreg voice prosthesis. The global QoL was rated as satisfying with a mean value of 62. The analysis of the specific questionnaire showed mostly a limitation of smell. Patients, whose treatment was longer than five years ago, showed a slight improvement in the global QoL. Overall we could not find a significant difference concerning the QoL between the two groups.In our study the QoL of laryngectomized patients was satisfying. The most common symptoms were problems with smell, cough and dyspnoea.

The etiology and factors influencing the prognosis of idiopathic sensorineural hearing loss are still in focus. To determine pathogenetic relevant factors, a detailed clinical characterization of patients with idiopathic sudden sensorineural hearing loss remains to be performed.The history of 103 patients who presented with a sudden sensorineural hearing loss and received a standard treatment with prednisolone und pentoxyphylline (Stennert-Schema) has been investigated with a new questionnaire. In addition, audiological and serological investigations were analysed.A partial or total recovery of hearing after therapy was reported by 57 % of patients, on average 15 dB. Half of the patients sustained at least one recurrent idiopathic sensorineural hearing loss. In single cases, fibromuscular dysplasia and hypothyroidism in autoimmunthyroidism were detected. Additionally, smoking was identified as a disease modulating factor. The age of admission to the hospital was significantly reduced in the group of smokers compared to non-smokers (p = 0.02). Non-smokers reported more episodes of sensorineural hearing loss compared to smokers (p = 0.02) according to their higher age. One third of the patients reported a high level of noise exposure in private and business, which was related with the sudden sensorineural hearing loss.By collecting an exact medical history, in more than 50 % of cases etiological and predisposing factors of sudden sensorineural hearing loss can be detected which lead to further diagnostic investigations and therapies.

Utilising the enormous proliferation and multi-lineage differentiation potentials of somatic stem cells represents a possible therapeutical strategy for diseases of non-regenerative tissues like the inner ear. In the current study, the possibility of murine neural stem cells to contribute to the developing inner ear following blastocyst injection was investigated.Fetal brain-derived neural stem cells from the embryonic day 14 cortex of male mice were isolated and expanded for four weeks in neurobasal media supplemented with bFGF and EGF. Neural stem cells of male animals were harvested, injected into blastocysts and the blastocysts were transferred into pseudo-pregnant foster animals. Each blastocyst was injected with 5-15 microspheres growing from single cell suspension from neurospheres dissociated the day before. The resulting mice were investigated six months POST PARTUM for the presence of donor cells. Brainstem evoked response audiometry (BERA) was performed in six animals. To visualize donor cells Lac-Z staining was performed on sliced cochleas of two animals. In addition, the cochleas of four female animals were isolated and genomic DNA of the entire cochlea was analyzed for donor contribution by Y-chromosome-specific PCR.All animals had normal thresholds in brainstem evoked response audiometry. The male-specific PCR product indicating the presence of male donor cells were detected in the cochleas of three of the four female animals investigated. In two animals, male donor cells were detected unilateral, in one animal bilateral.The results suggest that descendants of neural stem cells are detectable in the inner ear after injection into blastocysts and possess the ability to integrate into the developing inner ear without obvious loss in hearing function.

Commonly used staging procedures often cannot predict the absence of lymphatic micro- metastases in squamous cell carcinoma (SCC) of the head and neck. Therefore in many cases an elective neck dissection (ND) is necessary. In the surgical therapy of melanoma or breast cancer the presence of metastases can be evaluated securely by identification and examination of the sentinel lymph node (SLN). The type of surgical procedure is usually chosen in regard to the histopathological result. The present study evaluates the applicability of this concept for SCC of the head and neck.Radioactive labeled micro-albumin particles were injected preoperatively around the tumor in 38 patients without proven metastases. Following the excision of the primary tumor the sentinel lymph node/s were detected and dissected and ND was completed. Histological examination of the tissue was performed to evaluate whether the SLN reflected the lymphatic status.In two cases (5.1 %) no SLN were detected. ND was completed in 32 cases. In nine cases (28.1 %) the SLN were infiltrated by the primary tumor. In 22 cases (68.8 %) SLN and ND revealed a N(0) stage. In one case (3.1 %) we could not identify a metastasis because of the anatomical closeness of the SLN to the primary. The negative predictive value was 96 %.Predictive value regarding metastases to the neck was higher with the detection of SLN than with conventional staging procedures. Whether the detection of a tumor-free SLN is an indication not to perform an elective neck dissection is a matter of discussion, especially under the aspect of the effective reduction of postoperative morbidity.

Rhinogenous brain abscesses usually originate from a frontal sinusitis, rarely from the ethmoidal system or the maxillary sinus. However, there are different pathways that can lead to the transfer of a maxillary infection to the endocranial compartment.A patient with frontal brain abscesses originating from a maxillary sinus infection is presented and diagnostic steps, therapy as well as pathophysiology are discussed.The venous plexus of the maxillary sinus drains through the posterior wall of the antrum of Highmore into the deep facial vein that leads into the pterygoid plexus and then through the rete foraminis ovalis into the cavernous sinus. In addition, numerous small veins perforate the osseous roof of the maxillary sinus and enter the orbit joining the superior or inferior ophthalmic vein. They are also connected to the cavernous sinus or the pterygoid plexus. A number of veins perforate the anterior wall of the maxillary sinus communicating with the angular vein that drains into the superior ophthalmic vein and into the cavernous sinus. From the cavernous sinus, the blood arrives at the deep middle cerebral vein that usually communicates through the white substance towards the brain's superficial venous system.The presence of these maxillo-cerebral venous anastomoses explains the spread of infection from the maxillary sinus to the white substance of the brain without any direct association with the base of the skull.

Rhinogene Hirnabszesse gehen meist von einer Stirnhohleneiterung aus, selter vom Siebbeinsystem, der Keilbeinhohle oder der Kieferhohle. Dennoch ist ein Entzundungstransfer von einem isolierten Kieferhohlenempyem zum Endokranium moglich. Anhand eines Patienten mit von der rechten Kieferhohle ausgehenden frontalen Hirnabszessen werden Diagnostik, Therapie und Pathophysiologie dargestellt. Der maxillare Venenplexus drainiert uber die Kieferhohlenhinterwand in die V. profunda faciei, die in den Plexus pterygoideus und weiter uber das Rete foraminis ovalis in den Sinus cavernosus einmundet. Weiterhin treten zarte Venen durch das Kieferhohlendach in die Orbita und drainieren uber die V. ophthalmica superior oder inferior in den Sinus cavernosus. Schlieslich durchsetzen venose Gefase die Kieferhohlenvorderwand und munden in die V. angularis ein, von wo uber die V. ophthalmica superior eine Verbindung zum Sinus cavernosus besteht. Vom Sinus cavernosus gelangt das Blut in die V. media profunda cerebri, die durch das Marklager verlaufende anastomotische Verbindungen zum oberflachlichen Venensystem des Gehirns aufweist. Das Vorhandensein dieser maxillozerebralen Verbindungen ist eine Erklarung fur den Entzundungstransfer von der Kieferhohle in das Marklager, auch ohne direkten Nachbarschaftskontakt zur Schadelbasis.

During the last few years, several laser systems have been applied for procedures in middle ear surgery. In this study, we determined the technical parameters for the dissection of the middle ear ossicles with the CO(2) laser and analyzed the histological findings.The malleus necks of 16 human temporal bones were dissected under standardized conditions using a CO(2) laser with a power output between 35 and 55 kW/cm(2). The specimens were fixed and histological probes of 50- micro m thickness were prepared.The laser outputs led to crater diameters from 0.14 to 0.55 mm. As an analogy between laser energy and thermal tissue destruction, three zones of thermal damage were differentiated: a cinder zone, a carbonization zone, and a zone of dehydration. The metrical dimensions of these zones did not show any correlation to the applied laser energy.The data of this study show that commercially available CO(2) lasers are sufficient for a safe and effective partial resection of middle ear ossicles using a power output of 35 kW/cm(2).

The hair cells (HCs) are the most vulnerable elements in the cochlea and damage to them is the most common cause of sensorineural hearing loss (SNHL). Understanding the intracellular events that lead to the death of HCs is a key to developing protective strategies. Recently, it has been shown that the c-Jun-N-terminal kinase (JNK) pathway is activated in HCs in response to aminoglycosides and CEP-1347, an inhibitor of the JNK signaling pathway protected HCs from ototoxicity. We have studied another inhibitor (CEP-11 004) of this signaling pathway in its ability to protect HCs from aminoglycoside ototoxicity in vitro. Organ of Corti explants from p5 rat basal turns were maintained in tissue culture and treated with CEP-11 004 for 12 hours. They were then treated with CEP-11 004 plus gentamicin for 72 hours. Significantly less HC death was observed compared to gentamicin alone. CEP-11 004 alone had no effect on HCs. We conclude that the JNK signaling pathway plays a role in aminoglycoside ototoxicity signaling.

During the last years, various groups of growth factors have been identified to influence spiral ganglion cell survival and neurite extension in the mammalian cochlea. To evaluate and compare the effects of different growth factors, a precise histomorphometrical analysis of neurite outgrowth patterns has to be applied. The here presented technique is compared to already published methods, that only approximately estimate the neurite length.A software has been developed to analyse digitalised scans of spiral ganglion cells and to measure the length of the neurites. Therefore, the neurites are being separated in any given number of straight lines. The totals of these lines can then be added like a polygon. This polygon method was compared to a semi-quantitative procedure in which the neurite length was determined by concentric circles that were crossed by the neurites in a certain distance. The accuracy of both methods was analysed. Both methods were performed in 20 specimen of neonatal rat spiral ganglion cells after in vitro stimulation with neurotrophic factors.The semi-quantitative method has shown to involve a systematic error between +/- 10 to 15 %. The polygon method, on the contrary, has a systematic error of around +/- 1 %, which admits much more accurate measurement of spiral ganglion neurite outgrowth.With the described polygon method, spiral ganglion neurite growth patterns in cell culture studies can be characterised more precisely and, thus, helps to better differentiate the action domain of neurotrophic factors.

Phosphatidylinositol 3-kinase (PI3K) is considered to be an important enzyme in cell signaling, mediating certain aspects of neurotrophin signals from the cell surface receptor to the nucleus.The participation of PI3K in the mediation of neurotrophin-induced effects in the spiralganglion (SG) of neonatal rats was investigated in vitro. SG explants were stimulated with neurotrophin (NT)-3 and treated with Wortmannin, a specific inhibitor of PI3K. After fixation and immunhistochemical staining, the growth of the SG neurites was evaluated.Stimulation with NT-3 lead to significant increases in number and length of neurites, when compared to non-stimulated controls. Treatment of NT-3 stimulated SG explants resulted in a dose-dependent reduction of both parameters, whereas the neurite growth of non-stimulated control explants was not significantly influenced by the incubation with Wortmannin.The results demonstrate that neurotrophin-induced neurite growth from SG explants can be modulated with the PI3K inhibitor Wortmannin and indicate that PI3K is a key enzyme in the mediation of NT-3 effects in cochlear neurons. These observations together with results of previous studies suggest that the activation of PI3K as well as Ras and MEK are essential for neurite growth in cochlear neurons. Further knowledge of cell signaling mechanisms influencing SG neurite growth could lead to new therapeutical strategies for the treatment of inner ear diseases.

The case of an 87-year old man with widespread prostatic cancer is reported. During the autopsy macroscopically visible metastases were found within the frontal sinuses. These tumor masses destroyed the posterior osseous wall of the frontal sinus and formed polypoid bulging masses. In contrast to the macroscopically unaffected mucous membrane of the sphenoid sinus the maceration specimen of the skull base demonstrated a spongious-mossy, osteoplastic metastasis, lining the sphenoid sinus like a tapestry. This affection started from an exhaustive osteoplastic metastasis within the clivus. No metastases could be found in both antrums or the ethmoids. Retrospectively no symptoms from the paranasal sinuses could be eruated, only occasional pain of the frontal bone. The review of the world literature with 123 reports revealed 169 cases. Renal cell carcinomas most frequently metastasize into the paranasal sinuses (67 cases), followed by bronchogenic carcinomas (15 cases). Thyroid cancers and cancers of the mammary gland are responsible for 13 respectively 14 cases. The prostate also adds 12 cases. The paranasal sinuses are affected in diminishing frequency: maxillary sinus (55 cases), sphenoid sinus (37 cases), ethmoidal cells (23 cases) and frontal sinus (15 cases). In 38 cases exhaustive metastases affecting two or more paranasal sinuses are reported. The statement of literature, that metastases affecting the paranasal sinuses are much more frequent than reported, cannot be supported by our study, because the intensive autoptic investigation of 50 skulls of patients suffering from widespread cancers revealed no further cases of metastatic processes of the paranasal sinuses.

Transient expression by hair cells, increasing levels of FGF-1 mRNA in neonatal rat spiral ganglion neurons and strong expression in adulthood, make FGF-1 a candidate to be associated with development and maintenance of the mammalian spiral ganglion. To test this hypothesis, dissociated spiral ganglion cells from 5 day old rats were cultured in the presence of FGF-1 at 100 ng/ml plus heparan sulfate proteoglycans (HSPG) at 500 ng/ml for 72 hours. Spiral ganglion cells incubated with FGF-1/HSPG achieved an average neurite length of 323 microns while control cells gained an average neurite length of 203 microns. The results of this study are consistent with our previous findings in whole spiral ganglion explants (3) where FGF-1 incubation significantly stimulated neurite outgrowth at about the same range. However, stimulation of neurite outgrowth in dissociated spiral ganglion cells suggests that FGF-1 directly binds to FGF receptors on the surface of spiral ganglion neurons and/or neurites instead of acting via intermediate cells such as glia. Since FGF receptor mRNA was found to be expressed only at very low levels in neonatal spiral ganglion neurons (7) it is possible that the receptors are highly localized, perhaps to neurite growth cones. Alternatively, an unknown FGF receptor or splice variant may be expressed in these cells. Adequate FGF-1 application to the human inner ear may stimulate spiral ganglion cell survival and neurite extension after hair cell loss in patients suitable for cochlear implant treatment. By creating a closer contact between spiral ganglion cells and the electrode, FGF-1 might also improve the efficacy of cochlear implants.

Haemangiopericytomas are rare vascular neoplasms which show either slow local tumour growth or aggressive progression in size with a high tendency of recurrence and metastasis. Manifestations of haemangiopericytomas in the area of the nose and sinuses are supposed to have a relatively benign course. To date clinical and histological parameters for prognosis are uncertain. Therefore in a quite large number of cases only the clinical course allows to evaluate the dignity of a haemangiopericytoma.We present our experience with five haemanglopericytomas in contact with the skull base out of a total number of 457 skull base tumours. The site of origin of these five haemangiopericytomas were: nasal septum, pterygopalatine fossa, oronasopharynx, temporal bone, and parotid gland. All neoplasms showed primary or recurrent tumor in contact with the skull base and an intracranial extension was observed twice. One patient died postoperatively of a cerebral infarction. Three patients showed one or more recurrences which were treated surgically. In one case 5 recurrences occurred. Despite of 4 surgical procedures within a period of 15 months, the tumour could be controlled only for a short period of time, and the patient died 16 months after the first operation.One has to consider that haemangiopericytomas of the head and neck show a potential malignant course. The vascular tumor may recur decades later. Adequate therapy and life-long follow-up are therefore mandatory in haemangiopericytomas. Complete surgical resection of the tumour is usually the treatment of choice, in spite of the high degree of surgical skill required, especially in advanced tumour and in case of recurrence.