Complexity of PEComas : Diagnostic approach, molecular background, clinical management.

Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.

[Unilateral diseases of the maxillary sinus]. / Einseitige Erkrankungen der Kieferhöhle.

Unilateral diseases of the maxillary sinus are among the most common rhinologic diagnoses. The diversity of these diseases can represent a challenge for the treating physician. The spectrum ranges from harmless maxillary sinus cysts that seldom require treatment, to highly aggressive malignant tumors. Special attention should be given to the management of inverted papilloma. These benign tumors are characterized by high recurrence rates and the potential for malignant transformation. The key to minimizing recurrence is precise surgical intervention. Other unilateral maxillary sinus diseases such as the antrochoanal polyp and the fungus ball (aspergilloma) are also discussed in depth.

[Diagnosis and management of vascular malformations : Interdisciplinary teamwork in demand]. / Diagnostik und Management von Gefäßmalformationen : Interdisziplinäres Teamwork gefragt.

Vascular anomalies are very rare, but can occur in children and adults in almost every region of the body. Due to the complexity of this disease, the path to a definitive diagnosis is often difficult. It requires interdisciplinary teamwork with close exchange of information between the individual treatment partners to reach the correct diagnosis and then to start the best therapy. This article provides an overview of the main types of vascular malformations from a clinical, imaging, and histological point of view, following the current classification of the International Society for the Study of Vascular Anomalies (ISSVA).

[Complexity of PEComas : Diagnostic approach, molecular background, clinical management (German version)]. / Komplexität von PEComen : Diagnose, Molekulargenetik, klinisches Management.

Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.

[Anteromedial maxillectomy for improvement of nasal breathing : Advanced procedure in surgery of the lateral nasal wall]. / Anteriomediale Maxillektomie zur Verbesserung der Nasenatmung : Erweiterte Verfahren in der Chirurgie der lateralen Nasenwand.

The aim of classical surgical correction for nasal breathing impairment is to harmonically extend the physiological space in the nose by an operation of the nasal septum and inferior nasal turbinate. In this way the airflow character should be maintained and the mucosa protected in order not to endanger the respiratory function of the nose. This article presents an operative approach developed stepwise a few years ago in which the different operative steps are carried out depending on the individual anatomical situation and the underlying mucosal disease. The focus is on partial anteromedial maxillectomy.

[Recognition and prevention of problems in lacrimal duct surgery]. / Erkennung und Vermeidung von Schwierigkeiten bei der Tränenwegschirurgie.

Surgical management of lacrimal duct obstruction beyond the canaliculi proves to be a promising endeavor in most cases. To realize the full potential of endonasal dacryocystorhinostomy, some aspects of diagnosis and differential indication setting should be considered in order to avoid errors and problems during patient selection, execution of the technical procedure, and communication with ophthalmologists. These issues are described according to the clinical management of patients; current literature is cited.

[Diagnosis and treatment of Osler's disease]. / Diagnostik und Therapie des M. Osler.

Osler's disease is an autosomal dominant hereditary syndrome which belongs to the group of orphan diseases. Affected patients suffer primarily from severe epistaxis. Diagnosis is based on the Curaçao criteria and molecular genetic tests. Organ manifestations can be found in the form of arteriovenous shunts in the lung, liver, and gastrointestinal tract; more rarely also in the central nervous system (CNS) and other parts of the body. Many patients with gastrointestinal and other organ manifestations are frequently clinically asymptomatic; therefore, organ screening is essential to avoid later complications and should be performed in centers with particular expertise. No curative therapy currently exists. From the otolaryngologist's perspective, nasal mucosa treatments and endonasal laser applications are important and effective therapeutic approaches to epistaxis. Pharmacological interventions are focused on compensation of haploinsufficiency as well as antiangiogenetic approaches. Severe side effects have to be considered.

Orbital floor fracture repair: the endonasal approach.

To avoid the dangers associated with lower eyelid approaches to the orbital floor and to improve visualization, we propose an endoscopic procedure for orbital floor fracture reduction and osteosynthesis using endonasal access via the medial maxillary sinus wall. The technique of endoscopic, endonasal transantral surgery is described, together with a retrospective analysis of 17 patients who had undergone this surgical procedure in the Department of Otorhinolaryngology, University of Regensburg, between July 2013 and June 2016. Fractures without infraorbital margin involvement were successfully repaired and enophthalmos and/or diplopia were corrected in all cases. The endonasal approach described here allows orbital floor fractures to be repaired without injury to the eyelid apparatus. Visualization, in particular across the orbital floor as far as the palatine process, appears to be superior to that achieved with other approaches. The increased time required for the procedure and the difficulties of manipulation within a confined space are offset by rapid wound healing without ocular swelling and a minimal risk of complications.

[Circadian rhythm : Influence on Epworth Sleepiness Scale score]. / Zirkadianer Rhythmus : Einfluss auf den Punktwert der Epworth-Schläfrigkeits-Skala.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is frequently used to determine daytime sleepiness in patients with sleep-disordered breathing. It is still unclear whether different levels of alertness induced by the circadian rhythm influence ESS score. OBJECTIVE: The aim of this study is to investigate the influence of circadian rhythm-dependent alertness on ESS performance. MATERIALS AND METHODS: In a monocentric prospective noninterventional observation study, 97 patients with suspected sleep-disordered breathing were investigated with respect to daytime sleepiness in temporal relationship to polysomnographic examination and treatment. The Karolinska Sleepiness Scale (KSS) and the Stanford Sleepiness Scale (SSS) served as references for the detection of present sleepiness at three different measurement times (morning, noon, evening), prior to and following a diagnostic polysomnography night as well as after a continuous positive airway pressure (CPAP) titration night (9 measurements in total). The KSS, SSS, and ESS were performed at these times in a randomized order. RESULTS: The KSS and SSS scores revealed a circadian rhythm-dependent curve with increased sleepiness at noon and in the evening. Following a diagnostic polysomnography night, the scores were increased compared to the measurements prior to the night. After the CPAP titration night, sleepiness in the morning was reduced. KSS and SSS reflect the changes in alertness induced by the circadian rhythm. The ESS score war neither altered by the intra-daily nor by the inter-daily changes in the level of alertness. CONCLUSION: According to the present data, the ESS serves as a reliable instrument to detect the level of daytime sleepiness independently of the circadian rhythm-dependent level of alertness.

[Trauma of the midface]. / Traumatologie des Mittelgesichts.

Fractures of the midface pose a serious medical problem as for their complexity, frequency and their socio-economic impact. Interdisciplinary approaches and up-to-date diagnostic and surgical techniques provide favorable results in the majority of cases though. Traffic accidents are the leading cause and male adults in their thirties are affected most often. Treatment algorithms for nasal bone fractures, maxillary and zygoma fractures are widely agreed upon whereas trauma to the frontal sinus and the orbital apex are matter of current debate. Advances in endoscopic surgery and limitations of evidence based gain of knowledge are matters that are focused on in the corresponding chapter. As for the fractures of the frontal sinus a strong tendency towards minimized approaches can be seen. Obliteration and cranialisation seem to decrease in numbers.Some critical remarks in terms of high dose methylprednisolone therapy for traumatic optic nerve injury seem to be appropriate.Intraoperative cone beam radiographs and preshaped titanium mesh implants for orbital reconstruction are new techniques and essential aspects in midface traumatology. Fractures of the anterior skull base with cerebrospinal fluid leaks show very promising results in endonasal endoscopic repair.

[Aerosinusitis: part 1: Fundamentals, pathophysiology and prophylaxis]. / Aerosinusitis: Teil 1: Grundlagen, Pathophysiologie und Prophylaxe.

The relevance of aerosinusitis stems from the high number of flight passengers and the impaired fitness for work of the flight personnel. The frontal sinus is more frequently affected than the maxillary sinus and the condition generally occurs during descent. Sinonasal diseases and anatomic variations leading to obstruction of paranasal sinus ventilation favor the development of aerosinusitis. This Continuing Medical Education (CME) article is based on selective literature searches of the PubMed database (search terms: "aerosinusitis", "barosinusitis", "barotrauma" AND "sinus", "barotrauma" AND "sinusitis", "sinusitis" AND "flying" OR "aviator"). Additionally, currently available monographs and further articles that could be identified based on the publication reviews were also included. Part 1 presents the pathophysiology, symptoms, risk factors, epidemiology and prophylaxis of aerosinusitis. In part 2, diagnosis, conservative and surgical treatment will be discussed.

[Aerosinusitis. Part 2: Diagnosis, therapy and recommencement of flight duties]. / Aerosinusitis. Teil 2: Diagnostik, Therapie und Wiederaufnahme der Flugtätigkeit.

Aerosinusitis more frequently affects the frontal sinus than the maxillary sinus and mostly occurs during descent. Sinonasal diseases and anatomic variations leading to obstruction of paranasal sinus ventilation favor the development of aerosinusitis. This Continuing Medical Education (CME) article is based on selective literature searches of the PubMed database (search terms: "aerosinusitis", "barosinusitis", "barotrauma" AND "sinus", "barotrauma" AND "sinusitis", "sinusitis" AND "flying" OR "aviator"). Additionally, currently available monographs and further articles that could be identified based on the publication reviews were also included. In part 2, diagnostic measures, drug therapy, balloon dilatation and endoscopic sinus surgery are presented, along with a discussion regarding when flight attendants and pilots are able to resume their work. Endoscopic surgery to expand the natural drainage pathways of the affected sinuses with minimal surgical trauma to the healthy mucous membranes is largely successful.

[Sk2 guidelines"diagnosis and therapy of snoring in adults" : compiled by the sleep medicine working group of the German Society of Otorhinolaryngology, Head and Neck Surgery]. / S2k-Leitlinie "Diagnostik und Therapie des Schnarchens des Erwachsenen" : Vorgelegt von der Arbeitsgemeinschaft Schlafmedizin der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

These guidelines aim to facilitate high quality medical care of adults with snoring problems. The guidelines were devised for application in both in- and outpatient environments and are directed primarily at all those concerned with the diagnosis and therapy of snoring. According to the AWMF three-level concept, these represent S2k guidelines.A satisfactory definition of snoring does not currently exist. Snoring is the result of vibration of soft tissue structures in narrow regions of the upper airway during breathing while asleep. Ultimately, these vibrations are caused by the sleep-associated decrease in muscle tone in the area of the upper airway dilator muscles. A multitude of risk factors for snoring have been described and its occurrence is multifactorial. Data relating to the frequency of snoring vary widely, depending on the way in which the data are collected. Snoring is usually observed in middle-aged individuals and affected males predominate. Clinical diagnosis of snoring should comprise a free evaluation of the patient's medical history. Where possible this should also involve their bed partner and the case history can be complimented by questionnaires. To determine the airflow relevant structures, a clinical examination of the nose should be performed. This examination may also include nasal endoscopy. Examination of the oropharynx is particularly important and should be performed. The larynx and the hypopharynx should be examined. The size of the tongue and the condition of the mucous membranes should be recorded as part of the oral cavity examination, as should the results of a dental assessment. Facial skeleton morphology should be assessed for orientation purposes. Technical examinations may be advisable in individual cases. In the instance of suspected sleep-related breathing disorders, relevant comorbidities or where treatment for snoring has been requested, an objective sleep medicine examination should be performed. Snoring is not-at least as we currently understand it-a disease associated with a medical threat; therefore there is currently no medical necessity to treat the condition. All overweight patients with snoring problems should strive to lose weight. If snoring is associated with the supine position, positional therapy can be considered. Some cases of snoring can be appropriately treated using an intraoral device. Selected minimally invasive surgical procedures on the soft palate can be recommended to treat snoring, provided that examinations have revealed a suitable anatomy. The choice of technique is determined primarily by the individual anatomy. At an appropriate interval after the commencement or completion a therapeutic measure, a follow-up examination should be conducted to assess the success of the therapy and to aid in the planning of any further treatments.

Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer.

BACKGROUND: Activity of the tumour-suppressor gene PTEN is reduced in different types of cancer and implicates non-responsiveness to targeted therapy. This study evaluates the gene and protein status of PTEN in salivary gland carcinomas. METHODS: A total of 287 carcinomas of the major and minor salivary glands were investigated for phosphatase and tensin homologue located on chromosome 10 (PTEN) deletion and loss of PTEN expression using fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. Results were correlated to clinicopathological parameters, long-term survival, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (IHC and FISH) status of the tumours. RESULTS: Hemizygous deletions of PTEN were found in 35 out of 232 (15.1%) carcinomas, while homozygous deletions were observed in 17 out of 232 (7.3%) tumours. Phosphatase and tensin homologue located on chromosome 10 deletion was common in certain histological subtypes and especially homozygous deletion was associated with high-grade malignancy, lymph node metastases and unfavourable long-term prognosis (P<0.001). Loss of PTEN expression was present in 59 out of 273 (21.6%) carcinomas and was significantly correlated to genomic PTEN deletion, high-grade malignancy (P<0.001), increased tumour size (P=0.036), lymph node metastases (P=0.007) and worse disease-specific survival (P=0.002). Genomic PTEN deletion, in particular homogenous deletion (P<0.001) predominantly occurred in tumours with increased gene copy number of EGFR (60.0%) and/or amplification of HER2 (63.6%). Loss of PTEN expression was frequently found in tumours overexpressing EGFR (28.6%) and/or HER2 (52.6%). CONCLUSION: PTEN function is reduced in different types of salivary gland cancer indicating unfavourable prognosis. Its association with EGFR and HER2 signalling might affect targeted therapy.

Endoscopic sinus surgery training courses: benefit and problems - a multicentre evaluation to systematically improve surgical training.

BACKGROUND: The aim of this multicentre study was to systematically analyse the strengths and weaknesses in the surgical training for endoscopic sinus surgery (ESS) and identify measures that may improve training. METHODOLOGY: Using a structured questionnaire, 133 participants of ESS courses in seven centres in Germany, Switzerland and Australia were asked about their experiences during their dissection courses and how they perceived their course could be improved. RESULTS: Gaining confidence in handling of instruments and endoscopes was only a problem for participants with little experience in ESS. The majority of the participants, independent from their level of training, considered infundibulotomy and anterior ethmoidectomy as the easiest dissection steps, whilst surgery of the frontal sinus posed a considerable challenge for many surgeons even those with a higher level of training. Participants with and without ESS experience thought that emphasis on anatomy was the most important improvement that could be made during their surgical training. Virtually all participants stated that the course improved their anatomical knowledge, their surgical skills and their confidence when performing ESS. CONCLUSIONS: ESS dissection courses are considered beneficial by surgical trainees. Participants felt that more emphasis on sinus anatomy in conjunction with private study is essential to maximize their skills in surgical dissection. For beginners with ESS, an infundibulotomy and anterior ethmoidectomy were thought to be the best initial procedures to help develop endoscopic surgical skills.

[Bevacizumab in therapy-refractory epistaxis: case report of low-dose antibody therapy for hereditary hemorrhagic telangiectasia]. / Bevacizumab bei therapierefraktärer Epistaxis: Fallbericht einer niedrigdosierten, submukös injizierten Antikörpertherapie bei M. Osler.

We report on the submucosal injection of bevacizumab (Avastin) at a dose of 0.3 to 3.75 mg per side in a patient with hereditary hemorrhagic telangiectasia. Application of such low doses has not been described in the literature yet. Our case report shows the positive effect of low-dose bevacizumab on therapy-refractory epistaxis. No complications were caused by the bevacizumab treatment.

TIMolol nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia (HHT) - Study protocol of the prospective, randomized, double-blind, controlled cross-over TIM-HHT trial.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an inherited orphan disease, in which the absence of capillary beds between arterioles and venules lead to arteriovenous shunts. Epistaxis is the core symptom. Several case reports have described the nonselective beta-adrenergic receptor antagonist timolol as a successful treatment method of nosebleeds due in HHT patients. OBJECTIVE: TIM-HHT is a single-site, prospective, randomized, placebo-controlled, double-blind, cross-over study to investigate whether the efficacy of standard laser treatment of epistaxis in HHT patients can be increased by the additional use of timolol nasal spray (1 mg/d). METHODS: Twenty patients will be randomly allocated to one of two treatment sequences. Primary outcome is the severity of epistaxis determined by the Epistaxis Severity Score (ESS). Secondary outcomes are subjective satisfaction, quality of life, as well as the hemoglobin, ferritin, and transferrin levels of the participating patients. Safety outcome is assessed by means of pulse, blood pressure, and adverse events. CONCLUSION: TIM-HHT will evaluate the efficacy and safety of timolol as an additional treatment of epistaxis in HHT patients in a three-month trial period. Benzalkonium chloride is used as a placebo, which has no documented positive effect on the nasal mucosa and hence on epistaxis in HHT patients (in contrast to saline). TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00020994. Registered on 10 March 2020.

[Perioperative pain and anxiety in endoscopic sinus surgery]. / Perioperative Schmerzen und Ängste bei endoskopischen Nasennebenhöhleneingriffen mit konventioneller Nasentamponade.

BACKGROUND: Aim of this study was to evaluate the perioperative level of pain and anxiety for endoscopic sinus surgery, and to compare 3 different types of nasal packing. MATERIAL AND METHODS: Prospective, controlled, randomized study comparing different types of nasal packing in regard to perioperative anxiety and pain. Patients suffered from chronic rhinosinusitis with nasal polyps involving all paranasal sinuses. Patients daily evaluated by standardized questionnaires (FPI-R, KASA, STAI) and also visual analog scale for pain on 5 consecutive days before and after endoscopic sinus surgery of all paranasal sinuses. Nasal packings were removed on 2(nd) postoperative day. RESULTS: A total of 73 patients (polyvinyl acetate packing N = 14, glove packing N = 37, glove packing with breathing tubes N = 22) completed the study. Female gender, bad preoperative mood and absence of pain were associated with increased preoperative state anxiety based on regression analysis. Also, preoperative gathering of additional information from relatives and friends was correlated with increased preoperative anxiety. Patients had significantly minor preoperative anxiety if they could expect use of nasal packings with breathing tubes. CONCLUSION: Female patients, who gathered information about the operation from friends or relatives or patient in worse preoperative mood are at risk for increased state anxiety and should be identified prior to rhinosurgical procedures. Use of nasal packing with at least partially preserved nasal breathing is recommended in clinically anxious patients.

[S1 guideline on the "diagnosis and treatment of snoring in adults"]. / S1-Leitlinie "Diagnostik und Therapie des Schnarchens des Erwachsenen".

Due to the frequency of this phenomenon and the often considerable distress caused to the affected person, competent advice, diagnosis and treatment of snoring in adults is of particular importance. The aim of this guideline is to promote high-quality medical care for patients affected by this problem. According to the three-level concept of the AWMF, it corresponds to an S1 guideline. Prior to any therapeutic intervention, relevant sleep medical history, clinical examination, as well as a mandatory objective diagnostic measure are performed. Snoring is only treated if the patient asks for it. In general, invasive methods should be viewed critically and the patient should be advised correspondingly. In the case of surgical therapy, minimally invasive techniques are preferred. Reducing body weight (in the case of overweight snorers), abstinence from alcohol, nicotine and sleep medication, as well as maintaining a healthy sleep-wake cycle can be recommended from a sleep-medicine perspective, although convincing clinical studies are not yet available. Since evidence for the effectiveness of muscle stimulation or various methods for toning and training of the muscles of the floor of mouth is not available, these methods are not recommended. Snoring can be successfully treated with the use of an intraoral device; however, careful patient selection is important. Avoiding a supine position during sleep can be helpful in some cases. Only limited data is available on the success rates of the surgical approaches and long term data is often lacking, and not all techniques have been sufficiently evaluated from a scientific point of view. Nasal surgery is only indicated if the patient suffers from nasal obstruction. Extensive data supports the effectiveness of laser-assisted resection of excessive soft palate tissue (laser-assisted uvuloplasty, LAUP). In principle, however, such resections can be performed using other techniques. Placebo-controlled studies were able to prove the effectiveness of radiofrequency surgery of the soft palate. A reduction in snoring could also be achieved in many cases by means of soft palate implants with minimal post-operative morbidity. The indication for tonsillectomy and uvulopalatopharyngoplasty should be made cautiously due to the comparatively high morbidity associated with these procedures.