Targeting the microenvironment in the treatment of arteriovenous malformations.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31+ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects.

["Radical" versus "functional" surgery of the paranasal sinuses-A contradiction?] / "Radikale" vs. "funktionelle" Chirurgie der Nasennebenhöhlen ­ ein Widerspruch?

BACKGROUND AND OBJECTIVE: The terms "functional" and "radical" paranasal sinus surgery were often considered to be different operations which were mutually exclusive. This overview aims to look at the basics of these terms and surgical procedures and to work out the resulting surgical concepts for clinically relevant indications. MATERIAL AND METHODS: Selective literature analysis using the data base PubMed, corresponding textbooks and resulting secondary literature regarding functional and radical or extended paranasal sinus surgery. Similarly, the current literature regarding clinically relevant indications for sinus surgery were analyzed. RESULTS AND CONCLUSION: Modern pathophysiological knowledge, anatomically and pathophysiologically substantiated endoscopic surgical procedures and the usage of up to date technical possibilities have resulted in concepts which combine functional and so-called radical or extended surgery of the paranasal sinuses that complement each other and sometimes even overlap. The preoperative diagnosis and definition of underlying diseases are decisive and should be as precise as possible, as the extent and surgical details mainly depend on them: a sole creation of free drainage pathways, an additional creation of anatomical access for subsequent topical treatment or a complete (radical) removal of a pathological process.

[Fundamentals and practice of the application of nasal packing in sinonasal surgery]. / Grundlagen und Praxis der Anwendung von Nasentamponaden in der endonasalen Chirurgie.

BACKGROUND AND OBJECTIVES: This paper presents an overview on nasal packing materials which are available in Germany. The current literature is analyzed whether there are robust criteria regarding use nasal packing after sinonasal surgery, whether there are fundamental and proven advantages or disadvantages of products, and what this means in clinical practice. MATERIALS AND METHODS: Selective literature analysis using the PubMed database (key words "nasal packing", "nasal tamponade", "nasal surgery", "sinonasal surgery", or "sinus surgery"), corresponding text books and resulting secondary literature. RESULTS AND CONCLUSIONS: Because of systematic methodological shortcomings, the literature does not help in the decision-making about which nasal packing should be used after which kind of sinonasal surgery. In fact, individual approaches for the many different clinical scenarios are recommended. In principle, nasal packing aims in hemostasis, should promote wound healing, and should not result in secondary morbidity. Nasal packing materials should be smooth (non-absorbable materials), inert (absorbable materials), and should not exert excessive pressure. Using non-absorbable packing entails the risk of potentially lethal aspiration and ingestion. For safety reasons inpatient control is recommended as long as this packing is in situ. With other, uncritical packing materials and in patients with special conditions, outpatient control could be justified.

Closure of Nasal Septal Perforations Using a Diced Cartilage in Fascia Graft.

The spectrum of surgical techniques in the repair of nasal septal defects is wide. The objective of this study was to assess the feasibility of using a diced cartilage in fascia (DC-F) graft for successful closure of nasal septal perforations and to evaluate symptom reduction. This was a retrospective study of 18 patients undergoing surgical repair of symptomatic nasoseptal perforations of different etiologies using a DC-F graft from 2020 until 2021. The procedure was feasible in all of the 18 patients. Reconstruction of septal defects with a DC-F graft led to reduction of crust formation, reduction of epistaxis, and improvement of nasal breathing in 13 out of the 18 patients when seen for their 2-month follow-up. Reperforation occurred in three cases, leaving defects of 1, 7, and 5 mm in diameter. In one case, the reperforation was symptomatic. A DC-F graft proved to be a reliable and reproducible method for the closure of nasoseptal perforations of variable sizes, of different locations, and of different etiologies.

A third hand to the surgeon: the use of an endoscope holding arm in endonasal sinus surgery and well beyond.

BACKGROUND: Extended endoscopic endonasal operations of the sinuses and the frontal skull base require a bimanual action of the surgeon in many cases. Thus, typically an assistant guides the endoscope and centers the field of view. In this study, we investigate in which cases an endoscope holding arm can be used alternatively. MATERIALS AND METHODS: The electromagnetic system ENDOFIXexo was used in different surgical interventions of the paranasal sinuses and beyond questioning ergonomics and geometrical limitations. The realized degrees of freedom were documented, and a topography of possible applications compiled. RESULTS: The presented system is limited by the anatomy of the anterior ethmoid and dynamic working conditions in the sagittal direction. Especially in extended interventions in the posterior ethmoid, in which parts of the nasal septum have been resected and a static position of the endoscope is desired the surgeon can greatly benefit from the robotic arm. Moreover, through the high flexibility of the endoscopic arm surgeries of the pharynx and larynx were performed, questioning the current gold standard of microscope-assisted surgical procedures. CONCLUSION: Under the impression of an urging staff shortage and due to its unlimited patience, the ENDOFIXexo arm seems promising. Taking into account the complex anatomy and the limited access, we especially see a favorable field of application in the surgery of the pituitary gland and skull base tumors.

Safety and Efficacy of Blue Light Laser Treatment in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a hereditary condition that is associated with arteriovenous malformations. A common site for these malformations is the nasal mucosa, which is associated with severe epistaxis and debilitation for affected patients. We evaluated the efficacy and safety of blue light laser technology in treating these endonasal manifestations in a retrospective chart analysis. Additionally, we compared blue light laser technology to bipolar coagulation in an animal model. STUDY DESIGN/MATERIALS AND METHODS: We performed a retrospective chart analysis of all patients that were diagnosed with HHT and received endonasal blue light laser treatment between 10/2017 and 04/2019. In addition, we performed bipolar or blue light laser coagulation of all macroscopically visible vessels on thyroid gland lobes (n = 4) from Dunkin-Hartley Guinea Pigs. Hematoxylin-eosin (HE) staining was then used to visualize depth and area of coagulation surrounding these vessels. RESULTS: One hundred and fifty-one treatments in 23 patients were analyzed. Under regular blue light laser treatment, quality of life (QOL), indicated on a visual analog scale from 1 to 10, gradually increased significantly from 5.6 ± 0.5 (before the first treatment) to 7.5 ± 0.9 (after the second treatment). Following this, QOL remained steady throughout additional treatments. Adverse effects were not recorded. HE staining showed that coagulation depth (162 ± 56 vs. 586 ± 192 µm) and area (74 ± 35 vs. 1015 ± 449 µm2 ) were significantly lower after laser treatment. CONCLUSION: Blue light laser therapy is safe and efficient in treating HHT. Damage to the surrounding tissue is significantly lower compared with bipolar coagulation. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

[Postoperative treatment following paranasal sinus surgery]. / Postoperative Versorgung bei Nasennebenhöhleneingriffen.

Postoperative care is a crucial aspect for the success of paranasal sinus interventions. Basic procedures include saline nasal wash, which should be started on the first postoperative day, topical steroids, and antibiotics in cases of infection. Medical treatment involves aspiration of secretion in the inferior meatus during the first week. Removal of scabs in the surgical field should be carried out under endoscopic control beginning at the second week. Intervals are scheduled individually. Occlusion of the nose for the time of epithelium regeneration provides a moist space in the ethmoid, which improves wound healing.

[Hygiene in ENT examination: Fluorescence study with overview of current recommendations]. / Hygiene bei der HNO-Untersuchung: Fluoreszenzstudie mit Übersicht der aktuellen Empfehlungen.

Increasing normative demands on patient safety and quality assurance measures, but also the problem of multi-resistant germs and pathogens with a high potential for infection, increase the need for hygienically correct work.In this study, hygienically relevant potential sources of contamination in ENT examinations were to be identified and possible improvement strategies examined.A complete ENT examination was performed by 5 examiners with different professional experience, whose gloves were wetted with fluorescent lotion prior to the examination. Contaminations especially on the examination unit and on the instruments were identified. The potential risk of transmission of pathogens to subsequent patients was assessed using a specially developed score. Various strategies to reduce identified contamination possibilities were developed and thought through.The score of the investigators was very high with an average of 87.4 points (±3.6). The implementation of individual hygiene measures during the examination process would lead to a significant reduction of the score and thus to an improvement in hygiene: No shaking of hands (81.8), additional disinfection of patient's chair (79.8), disinfection of important surfaces (69.8), provision of standard instruments (60.2) or all instruments (32.2), disinfection of all relevant surfaces and provision of all instruments (7.4).The results show very clearly that an ENT examination is a complex procedure from the point of view of hygiene. For reliable protection against possible transmission events, a structured bundling of hygiene measures is therefore necessary.

[The maxillary sinus via a prelacrimal approach as a gateway to the retromaxillary space and orbital floor]. / Die Kieferhöhle über den prälakrimalen Zugang als Portal für den retromaxillären Raum und den Orbitaboden.

Endonasal surgery has emerged as the standard procedure for the majority of nasal and paranasal sinus pathologies. However, some pathological changes beyond the maxillary sinus seem to be out of the instrumental range and are addressed by open approaches. The prelacrimal approach to the maxillary sinus published by Zhou and coworkers has stimulated a rapid development of various procedures in this field. In the current work, the possibilities of the prelacrimal approach are illustrated by means of three clinical cases. The prelacrimal approach enables isolated fractures of the orbital floor to be reconstructed without the risk of lower eyelid complications. Meningo- or encephaloceles in the far lateral aspects of the sphenoid sinus are comparatively well reached via endonasal, transantral, and transpterygoid approaches. Until recently, tumors beyond the maxillary sinus were the domain of open surgery, particularly when they extended laterally of the maxillary sinus. The technique of choice was either a Caldwell-Luc or a midfacial degloving approach. Many of these operations can now be performed via the endonasal prelacrimal approach, with lower morbidity and more rapid postoperative healing. The approach described herein is equal if not superior to the traditional approaches in terms of overview and accessibility.

[Stents and spacers in endoscopic endonasal sinus surgery]. / Stents und Platzhalter in der endoskopischen endonasalen Nasennebenhöhlenchirurgie.

In endonasal endoscopic sinus surgery continuous progress has been made in the last decade due to better understanding of microanatomy, gains in adjunctive medicative therapy and technical innovations. Moreover, continuous research and clinical trials on innovative stents and spacers with and without defined drug eluting features may be mentioned in this context. A narrative review of the current development status and its therapeutic options referring to the latter is presented.

Nasal septum configuration as a basis for novel septal splints.

The objective is to use anatomical determinations of nasal septum shape and surface area in adults as a design basis for silastic septal splints of universal size and fit and offering maximum possible surface coverage. The objective is also to devise a method of securing the septal splints, so that surface pressure on septal mucosa is distributed as evenly as possible while not interfering with capillary perfusion. Nasal septum area was determined in 21 Caucasian body donors, and nasal septum thickness was measured in 20 CT scans. Septal splints of universal size and shape were prepared from silastic sheeting. The holding force of various neodymium-iron-boron (NdFeB) magnets, and the surface pressure exerted by magnet-containing septal splints was calculated. These septal splints of novel design offer a satisfactory fit in routine clinical practice. The splints can be securely attached with built-in NdFeB magnets, and surface pressure can be distributed evenly across the nasal septum while not interfering with mucosal tissue perfusion. With their simple intranasal insertion, these magnet-containing septal splints of universal size and optimised shape offer maximum possible septum coverage following septoplasty/septorhinoplasty. The absence of interference with septal tissue perfusion means that they are likely to be associated with fewer postoperative complications and better outcomes.

Influence of temporary nasal occlusion (tNO) on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia (HHT).

The objective of the study was to evaluate the influence of temporary nasal occlusion (tNO) with hypoallergenic tape on the frequency and severity of epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). This prospective observational study included 20 HHT patients who were undergoing Nd:YAG laser therapy at regular intervals. Over a 3-month period, laser therapy was supplemented by tNO with hypoallergenic tape for 5 h/day on average. On a 0-10 numeric rating scale, the patients reported significantly greater satisfaction in epistaxis terms after tNO treatment, with mean scores of 5 before and 7 after 3-month tNO (p = 0.05). The Epistaxis Severity Score also fell significantly from a median of 3.59-2.43 after 3-month tNO compared with laser therapy alone (p = 0.01). The patients' hemoglobin levels remained stable during the study (median: 12.2 g/dL before tNO; median: 11.7 g/dL after tNO; p = 0.387). Overall, the present study confirms the positive influence of tNO on epistaxis in HHT patients and on subjective satisfaction. This simple and inexpensive strategy is therefore a helpful option, especially in addition to regular Nd:YAG laser therapy, and is recommended by the authors.

Depth-dependent changes of obstruction patterns under increasing sedation during drug-induced sedation endoscopy: results of a German monocentric clinical trial.

PURPOSE: Drug-induced sedation endoscopy (DISE) and simulated snoring (SimS) can locate the site of obstruction in patients with sleep-disordered breathing (SDB). There is clinical evidence for a change in collapsibility of the upper airway depending on the depth of sedation. So far, a dose-response relationship between sedation and collapsibility has not been demonstrated. METHODS: DISE and SimS were performed in 60 consecutive patients with SDB under monitoring of depth of sedation by BiSpectral Index® (BIS). Initially, SimS was conducted followed by DISE using bolus application of propofol. Sedation was performed up to a sedation level representing slow wave sleep (BIS = 40). The collapsibility of the upper airway was documented at decreasing sedation levels by an identical pictogram classification. RESULTS: For all levels and patterns of obstruction, a dose-dependent increase in the collapsibility of the upper airway was detected. A maximum collapsibility was achieved at sedation levels representing slow wave sleep. The collapsibility during SimS corresponded to light sleep stages and did not cover slow wave sleep. CONCLUSION: A dose-dependent change of patterns of obstructions can be observed during DISE under BIS monitoring indicating sedation depth. The obtained patterns of obstruction during DISE and SimS should thus be interpreted with regard to the sedation depth.

Evaluation of acoustic characteristics of snoring sounds obtained during drug-induced sleep endoscopy.

INTRODUCTION: Snoring sounds are discussed to contain acoustic information about their geneses. Nocturnal snoring can easily be recorded acoustically but it is difficult to visually verify its genesis. Contrary, snoring patterns induced by drug-induced sleep endoscopy (DISE) can be visually differentiated. The aim of the study was to classify patterns of obstructions and vibration during DISE and to evaluate acoustic characteristics between these different patterns of snoring. METHODS: DISE was performed in 41 male patients with sleep-disordered breathing. The recorded video sequences (n = 108) were classified visually at a mute mode in different patterns of snoring (velar, velar obstructive, tonsillar, post-apnoeic). The sound tracks of these subgroups were analysed and compared with regard to the parameters sound pressure level, loudness, sharpness, roughness, fluctuations strength and centre frequency. RESULTS: Obstructive snoring patterns revealed a higher loudness than non-obstructive patterns (>25 sone). Velar snoring showed more roughness (>150 cAsper) than tonsillar and post-apnoeic snoring and revealed the lowest centre frequency (<3000 Hz) of all patterns. Tonsillar snoring presented the highest sharpness (>1.6 acum) whereas post-apnoeic snoring revealed the largest fluctuation strength (>50 cVacil). CONCLUSION: Different snoring patterns induced by DISE can be classified visually, and an approach to differentiate them acoustically by means of psychoacoustic analyses is demonstrated. On the basis of these results, nocturnal snoring might also be differentiated by psychoacoustic algorithms which could be implemented in acoustic polygraphic screening devices in the future.

Diagnosis and treatment of snoring in adults-S2k Guideline of the German Society of Otorhinolaryngology, Head and Neck Surgery.

OBJECTIVES: This guideline aims to promote high-quality care by medical specialists for subjects who snore and is designed for everyone involved in the diagnosis and treatment of snoring in an in- or outpatient setting. DISCUSSION: To date, a satisfactory definition of snoring is lacking. Snoring is caused by a vibration of soft tissue in the upper airway induced by respiration during sleep. It is triggered by relaxation of the upper airway dilator muscles that occurs during sleep. Multiple risk factors for snoring have been described and snoring is of multifactorial origin. The true incidence of snoring is not clear to date, as the incidence differs throughout literature. Snoring is more likely to appear in middle age, predominantly in males. Diagnostic measures should include a sleep medical history, preferably involving an interview with the bed partner, and may be completed with questionnaires. Clinical examination should include examination of the nose to evaluate the relevant structures for nasal breathing and may be completed with nasal endoscopy. Evaluation of the oropharynx, larynx, and hypopharynx should also be performed. Clinical assessment of the oral cavity should include the size of the tongue, the mucosa of the oral cavity, and the dental status. Furthermore, facial skeletal morphology should be evaluated. In select cases, technical diagnostic measures may be added. Further objective measures should be performed if the medical history and/or clinical examination suggest sleep-disordered breathing, if relevant comorbidities are present, and if the subject requests treatment for snoring. According to current knowledge, snoring is not associated with medical hazard, and generally, there is no medical indication for treatment. Weight reduction should be achieved in every overweight subject who snores. In snorers who snore only in the supine position, positional treatment can be considered. In suitable cases, snoring can be treated successfully with intraoral devices. Minimally invasive surgery of the soft palate can be considered as long as the individual anatomy appears suitable. Treatment selection should be based on individual anatomic findings. After a therapeutic intervention, follow-up visits should take place after an appropriate time frame to assess treatment success and to potentially indicate further intervention.

Drug-induced sleep endoscopy and simulated snoring in patients with sleep-disordered breathing: agreement of anatomic changes in the upper airway.

Drug-induced sleep endoscopy (DISE) and simulated snoring (SimS) are performed as part of the diagnostic procedure in patients with suspected sleep-disordered breathing (SDB). Despite both techniques frequently performed, they have rarely been evaluated yet in terms of agreement of the obtained results. Both diagnostic procedures were performed consecutively in 40 patients with SDB and documented identically. The obtained data were analysed with respect to the agreement of both procedure at different levels of the oropharynx as well as different patterns of obstruction and vibration. The anterior-posterior collapsibility of the soft palate/uvula revealed a moderate agreement between SimS and DISE (κ = 0.42; 95 % CI 0.22-0.63). The dorsal shift of the tongue base agreed moderate for patients with an AHI below 10 (κ = 0.47) and above 25 (κ = 0.44) between SimS ad DISE. The lateral and circular pharyngeal collapsibility at velum and tongue base level did not agree between SimS and DISE, was higher for DISE and could be partially reversed by mandibular protrusion. Collapse patterns of the soft palate and uvula can be induced by SimS and resemble the patterns induced by DISE. The dorsalization of the tongue base can be simulated to a lower extent by SimS. Lateral and circular patterns of collapse at the upper and lower oropharynx induced by DISE do not seem to be simulated by SimS. SimS seems to be an additional method to screen the collapsibility of the soft palate and uvula prior to DISE.

Orbital compartment: effects of emergent canthotomy and cantholysis.

The objective of this study was to determine the effect of orbital decompression procedures on the intraocular pressure (IOP). The orbital compartment syndrome represents an emergency situation. Due to the elevated IOP vision loss may ensue. Several maneuvers including lateral canthotomy are discussed to reduce the IOP. Eight orbits were studied in a fresh frozen cadaveric model (4 specimens). Intraorbital volume was determined by CT volumetry. An orbital compartment syndrome was simulated by injecting viscous material into the orbit. Injected volumes were documented and lateral canthotomy, cantholysis, inferior and superior septolysis were performed. IOP and exophthalmometric measurements were obtained after each intervention. Controlled elevation of IOP was achieved in all specimens. IOP was partially reduced after performing a lateral canthotomy in eight orbits. IOP was significantly and sufficiently decreased under 20 mmHg by inferior cantholysis in seven orbits. An additional superior cantholysis was necessary in two orbits to achieve a complete decompression. Inferior or superior septolysis were not needed to further reduce the IOP. Lateral canthotomy must be followed by an inferior cantholysis to successfully decompress an orbital compartment syndrome in the majority of cases. Occasionally, superior cantholysis may generate additional benefit. Additional inferior and superior septolysis were not shown to provide a beneficial effect when performed after canthotomy and cantholysis.

Frontobasal Fractures.

Frontobasal fractures occur in up to 24% of head injuries and often require a multidisciplinary approach. Besides the common bone fractures, the complex anatomy can cause damage to the sense of vision and smell. Further possibly lethal complications such as cerebrospinal fluid leak followed by meningitis or internal carotid bleeding can follow. Diagnostic and treatment options are reviewed with a focus on the endoscopic endonasal approach.

[Nasopharyngeal carcinoma. Brush biopsy with EBV-PCR is suitable as a screening test]. / Nasopharynxkarzinom. Bürstenbiopsie mit EBV-PCR eignet sich als Screeningtest.

The nasopharyngeal carcinoma (NPC) is closely associated with the Epstein-Barr virus (EBV) infection. Because each tumor cell in a patient regardless of histological subtype contains an identical copy of the viral clone, the virus is easily detectable at early pre-invasive lesions. Nevertheless, the nasopharyngeal carcinoma is still usually diagnosed late, often not until they exhibit infested lymph nodes and / or distant metastases have occurred. Canadian scientists have now discovered and analyzed a new screening method.