AQP1, AQP5, Bcl-2 and p16 in pharyngeal squamous cell carcinoma.

OBJECTIVE: This study aimed to link expression patterns of AQP1, AQP5, Bcl-2 and p16 to clinicopathological characteristics of oro-hypopharyngeal squamous cell carcinomas. METHODS: Immunohistochemical expression of AQP1, AQP5, Bcl-2 and p16 was investigated in 107 consecutive oro-hypopharyngeal squamous cell carcinoma cases. Molecular interrelationship and correlations with clinicopathological parameters and survival were computed. RESULTS: AQP1 was expressed exclusively by a subgroup of basaloid-like squamous cell carcinomas. AQP5 was detected in 25.2 per cent of the samples, showing significant association with the absence of p16 and Bcl-2 (p = 0.018; p = 0.010). In multivariate analysis, overexpression of p16 was significantly correlated with favourable overall survival (p = 0.014). CONCLUSION: AQP5 defined a subset of patients with Bcl-2-negative and p16-negative tumours with a poor clinical outcome. AQP1 was found to be a marker of a subgroup of aggressive basaloid-like squamous cell carcinomas. These findings suggest that AQP1 and AQP5 are interesting candidates for further studies on risk group classification and personalised treatment of oro-hypopharyngeal squamous cell carcinomas.

[Penetrating injuries of the head and neck region - a potentially life threatening situation]. / Penetrierende Verletzungen der Kopf-Hals-Region - Eine Potentiell Lebensbedrohliche Situation.

UNLABELLED: Penetrating Injuries of the Head and Neck Region - A Potentially Life Threatening Situation Background: Cuts, stabs and gunshot wounds in the head and neck region are potentially life-threatening because of the high risk of vascular lesions. A consistent emergency management is usually based on an operative exploration of the wound with effective reconstruction of viable structures. PATIENTS AND METHODS: Various penetrating injuries of the head and neck region are described in 11 cases with respect of age, gender, course of events of injury, type of injury, involved structures, diagnostic and operative procedures and outcome and compared with current literature and guidelines. RESULTS: In 10 of 11 patients, in the context of an interdisciplinary emergency room management, CT angiography was performed following clinical examination. A surgical exploration and wound treatment was performed in 9 of these patients. The common carotid artery, the external carotid artery and large venous blood vessels of the neck were injured in 2 cases respectively. None of the patients deceased or suffered permanent damage. CONCLUSION: The outcome of deep head and neck lesions with relevant vascular trauma is determined by a rapid and interdisciplinary approach. A rapid, systematic and interdisciplinary approach in specialized trauma centers has a significant role in ensuring that patients with penetrating wounds in the head and neck -region rarely die due to their serious injury or their consequences.

[Treatment of recurrent epistaxis by artery ligation: up to date or old fashioned?]. / Behandlung rezidivierender Epistaxis durch Gefäßligatur: zeitgerecht oder überholt?

UNLABELLED: Treatment of Recurrent Epistaxis by Artery Ligation: Up to Date or Old Fashioned? BACKGROUND: Despite the ongoing development in the field of endoscopic treatment techniques, recurrent epistaxis remains a challenge for otolaryngologists. The aim of the present study was to compare our own results of various interventions for the treatment of recurrent epistaxis. MATERIALS AND METHODS: From 2007 to 2013 we performed surgical treatment of recurrent epistaxis under general anaesthesia in 148 cases. While the majority of causes were idiopathic (n=98), epistaxis also occurred postoperatively (n=30), post-traumatically (n=7) or as a result of M. Osler (n=12). In 141/148 cases the treatment was performed by mono- or bipolar coagulation in the area of the bleeding source - this required an ethmoidectomy in 17 cases. In 19 cases the intervention was combined with a septoplasty. In 4 patients with recurrent bleeding of unknown origin, where electrocoagulation under general anaesthesia failed, we performed a clipping of the ethmoid- and/or the maxillary arteries in the pterygopalatine fossa. Following this intervention no further bleeding episodes occured. In further 3 patients, neuroradiological embolization was successfully performed. CONCLUSION: If conservative measures fail in the treatment of epistaxis, surgical treatment by electrocoagulation of the bleeding site under general anaesthesia is an effective intervention in 95% of cases. However for the remaining 5% where these measures have been proven to be ineffective, clipping of the ipsilateral anterior and posterior ethmoid- and/or the maxillar artery provides a treatment option being equally efficient as neuroradiological interventions.

[Bipedicled flap technique according to Schultz-Coulon using open approach for septal defect repair]. / Septumdefektverschluss: Ergebnisse der Brückenlappentechnik nach Schultz-Coulon in offener Technik.

BACKGROUND: The successful closure of a nasal septal perforation is a surgical challenge, which applies especially to large defects with a diameter exceeding 2.0 × 2.0 cm. This retrospective study presents results using open septoplasty via a transcolumellar approach and bipedicled flaps according to Schultz-Coulon for closure. RESULTS: In 45/50 patients the perforation was closed successfully (90%) (CI 0.82-0.98). The survey of patients showed significant improvement rates for all questioned parameters. CONCLUSIONS: In our hands the bipedicled flap technique combined with open access to the nasal septum yields good success rates for closure and consecutive improvement of life quality, also for large defects exceeding 2.0 × 3.0 cm. The open approach provides cosmetically excellent results based on the appropriate suture techniques and is advantageous concerning intraoperative overview and suture of the mucosal flaps. Additionally it can be easily combined with an open septorhinoplasty.

[Additional qualification in health economics--a pre-condition for ENT leadership positions?]. / Ist eine gesundheitsökonomische Zusatzqualifikation für HNO-ärztliche Leitungspositionen Voraussetzung?

BACKGROUND: The increasing medical-technical progress as well as the dramatic demographic changes cause problems with regard to rapid enlargement of medical service offers, allocation of resources and a financing shortfall in the German public health system. The economization in the German Health System can also be perceived in ENT departments. MATERIAL AND METHODS: After performing an internet search about the rapidly growing market for qualifications measures in health economics, we hence conducted an anonymous survey for ENT senior doctors and directors of the 34 German University Departments to evaluate their attitude towards, as well as their expectation of such an add-on qualification. RESULTS: Since the German government finalized the health care reform in the year 2000 such qualification measures rapidly developed: amongst others, 26 postgraduate, extra-occupational master programs have been inaugurated. The anonymous survey was answered by 105 ENT doctors (63 senior doctors, 27 vice professors and 15 directors). 63% out of these 105 colleagues considered such an add-on qualification to be mandatory. 41% of the colleagues were already "add-on qualified" in that field, only 10 of them by means of a study program. 71 of 105 colleagues (68%) considered the add-on qualification to be advantageous for their future personal career. With regard to the designated contents of the study program, "Staff Management" was even prioritized to "Hospital Financing" and "Cost Accounting". CONCLUSION: Aspects of management and a (health-) economical basic knowledge became an integral part of the daily routine for "first-line management doctors" also in (University) ENT-departments.

[Surgical management of persisting fistulas after salvage-laryngectomy]. / Chirurgisches Management der persistierenden Speichelfistel nach Salvage-Laryngektomie.

BACKGROUND: The salvage-laryngectomy (SLE) has compared to the laryngectomy a high risk for complications. The salivary fistula is the most frequent complication with an incidence range from 3% to 65% according to the literature. MATERIAL AND METHODS: From 2004-2011 we included in this study 16 patients with a recurrent or secondary T4a-squamous cell carcinoma (HNSCC) of the larynx or pyriform sinus undergoing a SLE. 6 HNSCC were located at the pyriform sinus (44%) and 9 at the larynx (56%). The aim of this retrospective study was to analyze the risk of developing a postoperative fistula after SLE as well as to present our surgical concept of persisting fistula treatment. RESULTS: 6 out of these 16 patients (38%) had a persisting fistula which needed a secondary surgical closure. In all of these cases we used a "sandwich"-concept which included a reconstruction of the pharynx by the pectoralis myofascial flap and another regional rotation flap as the deltopectoral flap or the latissimus dorsi flap for skin reconstruction of the neck. With this concept we were able to successfully close the fistula after the SLE in all 6 cases. CONCLUSION: By using our "sandwich"-concept we provide a multi-layered fistula closure with insertion of vital muscle tissue and a double epithelium. This guarantees a secure barrier to the saliva and prevents effectively a further fistula.

[Innovations in biomarker development: a pathway towards individualized cancer therapy?]. / Moderne Methoden der Biomarkerentwicklung: eine Chance für die individualisierte Tumortherapie?

Despite multiple medical and scientific achievements, cancer remains a leading cause of death worldwide. Next to imaging technologies, molecular methods for early detection and for monitoring of the course of disease are of increasing interest. Thus, over the past years numerous studies have focused on the identification of biomarkers for cancer diagnosis, prognosis and response to therapy. The study of biomarkers seems to pose a high degree of complexity because many different types of molecules may, in principle, serve as potential biomarkers. In addition, these molecules can be produced either by the tumor or by the tumor-host in response to the presence of cancer. In this review the authors will address several major topics encompassed by the field of biomarker research. They will discuss the primary sources from which biomarker candidates can be 'mined' as well as the technological or methodological challenges associated with identification of biomarkers. Furthermore, the review will focus on current biomarker candidates for head and neck squamous cell carcinoma (HNSCC), with particular interest on several molecules yielding potential relevance for detection and prognosis of this type of cancer. Finally, several biomarker candidates with predictive potential for the response to therapy of HNSCC patients will be discussed, since identifying such molecules is crucial for developing individually-tailored and improved therapeutic strategies.

[Epidermal cyst of the parotid gland]. / Epidermoidzyste als Raumforderung der Glandula parotis.

Epidermoid cysts of the parotid gland are rare. We report the case of a 60-year-old man with a cystic tumor of the right parotid gland. The patient had undergone ipsilateral middle ear surgery twice four years previously. The tumor was identified by computed tomography and ultrasonography and removed by total parotidectomy under suspicion of a parotid tumor. Histopathology revealed the diagnosis of an epidermal cyst. The differential diagnosis of a parotid tumor should include (iatrogenic) epidermoid cyst, in particular if there is a history of prior ear surgery via an endaural approach.

[Orbital and intracranial complications of acute sinusitis. Diagnostics and therapy in children and adolescents]. / Orbitale und intrakranielle Komplikationen akuter Sinusitiden. Diagnostik und Therapie bei Kindern und Jugendlichen.

Orbital and intracranial complications of acute sinusitis occur more frequently in the pediatric population compared to adults due to anatomic differences. Since the introduction of antibiotics the frequency of such complications has been dramatically reduced. Nevertheless, even in the era of modern antibiotics these complications continue to occur and it is therefore of utmost importance not only to know about these complications but also to include them in the differential diagnosis. Appropriate diagnosis mainly based on CT scanning or magnetic resonance tomography is the basis for a rapid and sufficient and if necessary interdisciplinary treatment. In this CME article the diagnostic and therapeutic interventions in four young patients suffering from orbital or intracranial complications due to acute sinusitis are described and discussed in the context of the current literature and a clinical algorithm is introduced.

In vitro chemosensitivity of head and neck cancer cell lines.

BACKGROUND: Systemic treatment of head and neck squamous cell carcinoma (HNSCC) includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. - METHODS: Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel) was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. - RESULTS: All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. - CONCLUSION: Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

[Diagnostic and prognostic biomarkers in head and neck squamous cell carcinoma]. / Tumormarker und Prognosefaktoren bei Plattenepithelkarzinomen der Kopf-Hals-Region.

Classical prognostic factors for squamous cell carcinoma of the head and neck (HNSCC) are based on general parameters such as tumor stage or histological grading and only allow for a rough estimation of the clinical course. However, predicting individual responses to treatment remains challenging and diverging clinical courses of same-stage HNSCC stage remain obscure. The need for a better understanding of the individual genomic or proteomic signature of HNSCC resulted in a great number of publications on novel biomarkers. Still, in most cancer centres therapy planning and risk appraisal are solely based on the classical factors with only a few exceptions such as HPV status in oropharyngeal carcinoma. Future improvements in biomarker research will probably be achieved with sets of various genomic and proteomic markers as provided by microarray technology. This review highlights the criteria for a successful biomarker candidate, gives an overview on the most important new biomarkers, and introduces the principles of genomic and proteomic biomarker chips.

[Space-occupying lesion of the thyroid cartilage]. / Raumforderung des Schildknorpels.

A 46-year-old patient had had a slowly growing progressive but painless prelaryngeal space-occupying lesion for approximately 1 year. In addition there was also a longstanding hyperuricemia with gout tophi on the metatarsal basal joints 1-5 of both hands. The extirpated tumor proved to be a gout tophus by histological examination. Although this is a rare occurrence it should be considered as the possible cause of a tumor if there is a corresponding case history.

The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma.

BACKGROUND: Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients' survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC. MATERIALS AND METHODS: One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. RESULTS: The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan-Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013). CONCLUSIONS: The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.

[Gigantic nasal tumor]. / Gigantischer Nasentumor.

A space-occupying lesion, which had been growing on the external surface of the nose of a 57-year-old man for 5 years was considered to most likely be an angiofibroma after surgical removal and histological examination, but the final clinical diagnosis was clearly a rhinophyma. This discrepancy is relevant for surgical treatment, because the vessel-rich tumor tended to substantial intraoperative bleeding.

No association of the NF-kappaB1 -94ins/delATTG promoter polymorphism with relapse-free and overall survival in patients with squamous cell carcinomas of the head and neck region.

The transcription factor, nuclear factor-kappaB (NF-kappaB) is known to play a major role in immune response, inflammation and, via apoptosis and proliferation, also in oncogenesis. Transcription of NFKB1, which encodes the subunit p50/p105 of NF-kappaB, seems to be influenced by an insertion/deletion polymorphism in its promoter region. Accordingly, the goal of this study is to investigate whether this polymorphism can serve as a putative prognostic marker in patients with Squamous Cell Carcinomas of the Head and Neck region (HNSCC). The prognostic value of the -94ins/delATTG NFKB1 promoter polymorphism was analyzed in an unselected series of patients treated with curative intent for HNSCC, including all tumor stages with different therapeutical regimens. Genotyping was performed by means of pyrosequencing, using DNA from paraffin-embedded tissue samples from 364 patients with a median follow-up of 61 (2-143) months. The various genotypes were correlated with relapse-free and overall survival, as well as risk, compared to healthy volunteers. The NFKB1 polymorphism was not related to risk of HNSCC. Kaplan-Meier curves revealed no significant association between the -94ins/delATTG alleles and survival or disease progression of patients with HNSCC. In conclusion, the results suggest that the investigated NFKB1 promoter polymorphism has no prognostic impact on risk or clinical course in HNSCC.

[Cutaneous basosquamous cell carcinoma]. / Basosquamöses Karzinom der Haut.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare malignancy with specific histopathological features of both basal cell (BCC) and squamous cell carcinoma (SCC). Therefore, the histological diagnosis is challenging. Due to its low incidence there is no consensus on the surgical management of BSC. PATIENTS AND METHODS: We describe the (immunohistological) diagnostic and therapeutic aspects of nine cases (8 male symbol : 1 female symbol, on average 68.6 years of age (range: 47-81)) of BSC. Of these, seven were located on the pinna, one on the forehead and zygomatic region and one in the retroauricular region. RESULTS: Immunochemical staining for epithelial membrane antigen was negative (apart from the typical areas of epithelial pearl formation) and BerEP4 was positive in all cases. Therapy consisted of partial removal of the pinna in four, and total removal in three cases. One patient was treated by partial removal of the auricle with superficial parotidectomy and ipsilateral neck dissection. In the case of the carcinoma on the forehead, a local excision was performed. The median follow-up was 45 months. One patient had a local recurrence. CONCLUSIONS: The histological diagnosis of BSC is confirmed by the use of EMA and BerEP4 immunohistological staining. Clinically, BSC is a rare, aggressive skin tumor. Despite the histological similarity to basal cell carcinoma, BSC has an imminent risk of metastasizing. Hence, therapy should be similar to that for SCC, taking into consideration the age and general state of the usually elderly patient.

[Myositis of the sternocleidomastoid muscle as a result of arthritis of the sternoclavicular joint]. / Myositis des Musculus sternocleidomastoideus infolge einer Arthritis des Sternoklavikulargelenks.

This article describes a rare case of a myositis of the sternocleidomastoid muscle due to an acute septic arthritis of the sternoclavicular joint. A 51-year-old male in reduced condition was admitted to the Department of Otorhinolaryngology with a one-week history of a painless swelling of the sternocleidomastoid muscle associated with recurrent fever. Physical examination was otherwise unremarkable. An intravenous antibiotic therapy was initiated without improvement of the process, accordingly a specific infection or a malignancy was ruled out by biopsy. The positron emission tomography and magnetic resonance imaging finally revealed the diagnosis of a septic arthritis of the sternoclavicular joint as the causal focus of the infection. After an extensive surgical debridement and under continued antibiotic therapy the patient made an uneventful recovery. The acute septic arthritis of the sternoclavicular joint is an uncommon infection with an insidious onset and is often unrecognized until it spreads to adjacent structures leading to serious complications. This case emphasizes that a myositis of sternocleidomastoid muscle can be caused by an ascending infection due to an acute septic arthritis of the sternoclavicular joint. Clinical course, diagnosis and treatment of this uncommon disease are reviewed in this article.

p16(INK4alpha)/exon 2 mutations in squamous cell carcinoma of the head and neck region.

CONCLUSIONS: In the samples of squamous cell carcinoma (SCC) of the head and neck region studied, mutations of exon 2 were quite rare. In contrast to the other three mutations, the G to C transversion on position 169 (Ala57Pro) has been found in several other studies before. Further investigations on mutations of the other exons 1alpha, 1beta and 3 are necessary. OBJECTIVE: Alterations of p16(INK4A) have been found in different types of human cancer cell lines. The aim of this study was to perform a screening for alterations of exon 2 of different SCCs of the head and neck region. METHODS: Forty samples of different SCCs of the head and neck were collected by biopsy or surgical resection. Exon 2 was amplified by using the primers 5'-GGTGAGGGGGCTCTACACAAG-3' and 5'-GTCTCCCGGGCTGAACTTTC-3'. DNA was sequenced with the primer 5'-CGGGCTGAACTTTCTGTGCT-3'. RESULTS: Mutations were found in 4 of our 40 samples. One sample showed a G to C transversion on position 169 (Ala57Pro), a second sample from the same patient confirmed the latter transition but also contained a transition C to T on position 179 (Ala60Val). Another patient showed an already known polymorphism, a transition G to A at position 442 (Ala148Thr). The third case was a transversion C to A on position 213 (Asn71Lys).