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.

[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.

["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.

Tracheoesophageal Fistula Closure in a Pediatric Patient Using a Supraclavicular Artery Island Flap.

Acquired tracheoesophageal fistulas can lead to large defects with fatal complications. Surgical management is challenging but necessary to prevent respiratory infections and poor weight gain. Therefore, a reliable and pliable flap like the pedicled supraclavicular artery island flap with its wide arc of rotation and robust vascularization is needed for reconstruction. We highlight the surgical technique and postoperative measures in managing a tracheoesophageal fistula due to button battery ingestion in a 9-month-old boy with the supraclavicular artery island flap. In summary, the supraclavicular artery island flap is a safe and successful tool for closure of large acquired tracheoesophageal fistulas in pediatric patients.

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.

The Folded Radial Forearm Flap in Lip and Nose Reconstruction-Still a Unique Choice.

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness.

TIMolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (TIM-HHT)-A Prospective, Randomized, Double-Blind, Controlled, Cross-Over Trial.

To date, there is no approved local therapeutic agent for the treatment of epistaxis due to hereditary hemorrhagic telangiectasia (HHT). Several case reports suggest the topical use of timolol. This monocentric, prospective, randomized, placebo-controlled, double-blinded, cross-over study investigated whether the effectiveness of the standard treatment with a pulsed diode laser can be increased by also using timolol nasal spray. The primary outcome was severity of epistaxis after three months, while the main secondary outcome was severity of epistaxis and subjective satisfaction after one month. Twenty patients were allocated and treated, of which 18 patients completed both 3-month treatment sequences. Timolol was well tolerated by all patients. Epistaxis Severity Score after three months, the primary outcome measure, showed a beneficial, but statistically nonsignificant (p = 0.084), effect of additional timolol application. Epistaxis Severity Score (p = 0.010) and patients' satisfaction with their nosebleeds after one month (p = 0.050) showed statistically significant benefits. This placebo-controlled, randomized trial provides some evidence that timolol nasal spray positively impacts epistaxis severity and subjective satisfaction in HHT patients when additively applied to standard laser therapy after one month. However, the effect of timolol was observed to diminish over time. Trials with larger sample sizes are warranted to confirm these findings.

HHT-Related Epistaxis and Pregnancy-A Retrospective Survey and Recommendations for Management from an Otorhinolaryngology Perspective.

Appropriate management of hereditary hemorrhagic telangiectasia (HHT) is of particular importance in females, as HHT-mediated modifications of the vascular bed and circulation are known to increase the risk of complications during pregnancy and delivery. This study was undertaken to evaluate female HHT patients' awareness of and experience with HHT during pregnancy and delivery, with a focus on epistaxis. In this retrospective study, 46 females (median age: 60 years) with confirmed HHT completed a 17-item questionnaire assessing knowledge of HHT and its pregnancy-associated complications, the severity of epistaxis during past pregnancies and deliveries, and the desire for better education and counselling regarding HHT and pregnancy. Results revealed that 85% of participants were unaware of their disease status prior to the completion of all pregnancies. Further, 91% reported no knowledge of increased pregnancy-related risk due to HHT. In regard to epistaxis, 61% of respondents reported experiencing nosebleeds during pregnancy. Finally, approximately a third of respondents suggested that receiving counseling on the risks of HHT in pregnancy could have been helpful. Findings suggest that awareness of HHT and its potential for increasing pregnancy-related risk is poor. Best practices in HHT management should be followed to minimize negative effects of the disorder.

Systemic therapy of necrobiotic xanthogranuloma: a systematic review.

BACKGROUND: Even though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature. OBJECTIVE: To review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies. METHODS: All reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases. RESULTS: The most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids. CONCLUSIONS: Corticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.

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.

Hereditary Hemorrhagic Telangiectasia: Success of the Osler Calendar for Documentation of Treatment and Course of Disease.

Hereditary hemorrhagic telangiectasia (HHT; Rendu-Osler-Weber syndrome) affects the capillary and larger vessels, leading to arteriovenous shunts. Epistaxis is the main symptom impairing quality of life. The aim of the Osler Calendar is to offer information about the extent of the systemic disease and the current state of treatment. A care plan with information on the rare disease and self-treatment of epistaxis was created. Organ examinations and ongoing treatments were recorded. A questionnaire documents the treatment success, including patient satisfaction, frequency of hemorrhage and hemoglobin levels. The patients using the Osler Calendar for at least one year (n = 54) were surveyed. Eighty-five percent of patients (n = 46) used the calendar to gain information about HHT. Seventy-two percent (n = 39) used the Osler Calendar for instructions on the self-treatment of nosebleeds. The calendar increased patients' understanding for the need for organ screenings from 48% (n = 26) to 81% (n = 44). Seventy-nine percent (n = 43) of patients confirmed that the Osler Calendar documented their therapeutic process either well or very well. Fifty-two percent (n = 28) saw an improvement in the therapeutic process due to the documentation. The Osler Calendar records the individual intensity of the disease and facilitates the communication between attending physicians. It is a tool for specialists to review treatment strategies. Furthermore, the calendar enhances patients' comprehension of their condition.

[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.

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.

[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.

QEVO® - A new digital endoscopic microinspection tool - A cadaveric study and first clinical experiences (case series).

BACKGROUND: The use of endoscopes in neurosurgery is well established, but the integration of a full high definition signaling, 45° angled endoscopic tool into a digital surgical microscope, is new. We report our first experiences in a cadaveric study and a clinical case series using the new microinspection tool QEVO® that serves as a plug-in feature for the recently launched KINEVO 900 digital visualization platform (CARL ZEISS MEDITEC, Oberkochen, Germany). For illustration purposes, we offer video footage. METHODS: The handling, workflow, and visualization patterns of the QEVO® microinspection tool were critically evaluated in cadaver specimens by simulating four standardized neurosurgical approaches: (1) pterional, (2) retrosigmoidal, (3) transsphenoidal, (4) and transcallosal. Similarly, we evaluated the QEVO® tool in corresponding clinical cases of (1) aneurysm clipping, (2) removal of cerebellar cavernoma, (3) and pituitary adenomectomy. RESULTS: In both the cadaveric study and clinical case series, the QEVO® tool was found to be beneficial in terms of high-quality visualization of fine structures and for displaying hidden anatomical details ("looking around the corner"). The handling was good, and the workflow was easy. However, the use of this tool was restricted by the lack of an external fixation and a working channel, the shortness of the tool, and the impossibility to switch to a 0° or 30° optic. CONCLUSION: Despite some restrictions, the QEVO® microinspection tool is an innovative, handheld, endoscopic tool that allows excellent additional visualization of the surgical field. In our opinion, this tool effectively enhances the modern neurosurgical armamentarium.

[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.