Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

[Local flap reconstruction techniques after frontal sinus drainage type II and III according to Draf]. / Lokale Lappenplastiken bei der Stirnhöhlendrainage Typ II und III nach Draf.

BACKGROUND: Extended endonasal endoscopic frontal sinus surgery is characterized by bone resection beyond the lamellae of the frontal sinus and is currently classified according to Draf as type IIa, type IIb, modified type III (also referred to as type IIc), and type III. This approach is indicated when the surgical goal cannot be achieved through complete removal of the anterior ethmoidal cells. Numerous studies indicate restenosis rates ranging from 7 to 36%, despite creation of maximal openings. Exposed bone, which tends to epithelize slowly with significant crusting and the risk of uncontrolled wound healing depending on the local environment and other factors, is considered a contributing factor. Covering the exposed bone with mucosa can significantly reduce the risk of restenosis. METHODS AND RESULTS: A variety of flap techniques for frontal sinus drainage in Draf III procedures are presented, including some variants that were part of presentations at the 2023 Congress of the European Rhinologic Society in Sofia, Bulgaria. These include combinations of free mucosal grafts, pedicled mucosal flaps, and hybrids combining both techniques. Additionally, the results of current studies are presented. CONCLUSION: The results and achieved opening areas in contemporary Draf III surgeries are significantly improved and larger compared to the early stages of these procedures. A multitude of published studies consistently demonstrate that outcomes are markedly improved with mucosal coverage. Depending on the prevailing anatomy, mucosal conditions, and the extent of the surgical intervention, the most suitable technique should be selected. Therefore, proficiency in various methods is crucial. The use of a flap technique (free, pedicled, or combinations thereof) should be defined as the standard when performing extended frontal sinus surgery (Draf IIb, IIc, III, or endonasal frontal sinus surgery [EFSS] 4-6).

[Decision-making in the treatment of chronic rhinosinusitis with nasal polyps in the era of biologics]. / Entscheidungsfindung bei der Behandlung der chronischen Rhinosinusitis mit Nasenpolypen in der Ära der Biologika.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies.

[Inverted papilloma of the nose and paranasal sinuses : Diagnosis, treatment, and malignant transformation]. / Invertiertes Papillom der Nase und Nasennebenhöhlen : Diagnostik, Therapie und maligne Transformation.

Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.

["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.

Partial Maxillectomy for the Improvement of Nasal Obstruction Can Be Combined with Septorhinoplasty.

We describe the (anteromedial) partial maxillectomy technique which can be used to address impaired nasal breathing in cases of significant protrusion of the frontal process of the maxilla into the nasal cavity, narrowing the nasal pathway. It fits to nasal physiology avoiding mucosal resection. It can be combined with surgery of the inferior turbinate. The described technique can be used in all forms of rhinoplasty.

The International Frontal Sinus Anatomy Classification (IFAC) and Classification of the Extent of Endoscopic Frontal Sinus Surgery (EFSS).

The frontal recess and frontal sinus anatomy can vary from simple to complex. The variations in the anatomy of the frontal recess and frontal sinus are considerable but almost all variations can be classified if the various cell patterns are analyzed. This consensus document was developed to improve the ability of the surgeon to understand these possible variations, plan the surgery, and communicate these complexities when teaching or reporting outcomes. Once the surgeon understands the anatomical pattern of the frontal sinus and recess cells, the extent of surgery can be planned. This document presents a classification of the extent of surgery based on the anatomical classification.

Comprehensive review on endonasal endoscopic sinus surgery.

Endonasal endoscopic sinus surgery is the standard procedure for surgery of most paranasal sinus diseases. Appropriate frame conditions provided, the respective procedures are safe and successful. These prerequisites encompass appropriate technical equipment, anatomical oriented surgical technique, proper patient selection, and individually adapted extent of surgery. The range of endonasal sinus operations has dramatically increased during the last 20 years and reaches from partial uncinectomy to pansinus surgery with extended surgery of the frontal (Draf type III), maxillary (grade 3-4, medial maxillectomy, prelacrimal approach) and sphenoid sinus. In addition there are operations outside and beyond the paranasal sinuses. The development of surgical technique is still constantly evolving. This article gives a comprehensive review on the most recent state of the art in endoscopic sinus surgery according to the literature with the following aspects: principles and fundamentals, surgical techniques, indications, outcome, postoperative care, nasal packing and stents, technical equipment.

Cysts of the maxillary sinus: a literature review.

BACKGROUND: Patients with isolated mucosal cysts of the maxillary sinus (MMC) often undergo surgical treatment despite the absence of relevant symptoms. Some physicians believe that MMC might increase in size and cause complications in the future. The anticipated value of this study is to consolidate and improve the understanding of MMC based on published data and to contribute to avoiding unnecessary interventions. METHODS: We performed a comprehensive review of the literature regarding definition, etiology, epidemiology, natural course, and best treatment of MMC. RESULTS: Among the 988 papers found in the literature search, 33 studies were selected to be relevant. Among those studies, there are only a few prospective controlled studies. Their prevalence rates range broadly from 3.6% to 35.6% according to different diagnostic methods as well as different indications for imaging. Recent prospective studies showed no correlation of MMC with sinonasal complaints or Lund-Mackay computed tomography (CT) score. The natural course is characterized by a decrease in size of MMC in 30% of the cases, an unchanged status in 50% to 60%, and an increase in 8% to 20% of the cases. CONCLUSION: MMC are harmless, mostly asymptomatic lesions that usually do not need surgical treatment. If surgery is indicated, endonasal endoscopic techniques should be the gold-standard approach.

Nasal irrigation as an adjunctive treatment in allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Saline nasal irrigation (SNI) is often recommended as additional nonpharmacologic treatment, having proven its efficacy in acute and chronic rhinosinusitis and for therapy after sinonasal surgery. To date, however, no systematic review or meta-analysis exists showing the influence of SNI on allergic rhinitis (AR). This study aimed to establish the impact of SNI on symptoms of AR in different patient groups. METHODS: We conducted a systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, and ISI Web of Science databases for literature published from 1994 to 2010 on SNI in AR. Prospective, randomized, controlled trials that assessed the effects of SNI on four different outcome parameters were included. The evaluation focused on primary (symptom score) and secondary parameters (medicine consumption, mucociliary clearance, and quality of life). RESULTS: Three independent reviewers chose 10 originals that satisfied the inclusion criteria (>400 participants total) from 50 relevant trials. SNI performed regularly over a limited period of up to 7 weeks was observed to have a positive effect on all investigated outcome parameters in adults and children with AR. SNI produced a 27.66% improvement in nasal symptoms, a 62.1% reduction in medicine consumption, a 31.19% acceleration of mucociliary clearance time, and a 27.88% improvement in quality of life. CONCLUSION: SNI using isotonic solution can be recommended as complementary therapy in AR. It is well tolerated, inexpensive, easy to use, and there is no evidence showing that regular, daily SNI adversely affects the patient's health or causes unexpected side effects.

Endoscopic frontal sinus drainage Draf type III with mucosal transplants.

BACKGROUND: This study was designed to evaluate the extent of restenosis that occurs after an endoscopic frontal sinus drainage Draf type III (Draf III; modified Lothrop procedure) using a modified technique with reconstruction of the frontal sinus drainage pathway with mucosal transplants, in combination with occlusive postoperative care. METHODS: Retrospective case series was performed with 24 consecutive patients undergoing Draf III drainage between 2005 and 2010 using the modified technique of covering the bare bone with mucosal transplants from the nasal septum. To ensure optimal moist wound healing, occlusion of the nose was realized by taping the nose for 2 weeks postoperatively. Frontal ostium measurements were done intraoperatively and at follow-up visits for a minimum of 12 months. Data on patient history, demographics, comorbidities, and computed tomography scans were collected. RESULTS: Mean follow-up was 25.6 months. Eight patients were lost to follow-up. Ninety-four percent of frontal sinus neo-ostia remained open. One patient needed revision surgery using an osteoplastic flap with obliteration. The frontal neo-ostium narrowed by an average of 36.9% from 20.5 × 12.5 to 15 × 9.6 mm. On average, three visits were needed for postoperative care. The patients did not experience significant pain throughout the postoperative healing time. CONCLUSION: The modified Lothrop procedure is a well-established technique in endoscopic sinus surgery to handle difficult frontal sinus drainage pathways or revision surgeries. The modified technique provides good results in combination with minimized postoperative care and morbidity. A comparative study would be necessary to show superiority to the standard method of Draf III.

Rhinitis sicca, dry nose and atrophic rhinitis: a review of the literature.

Despite the fact that many people suffer from it, an unequivocal definition of dry nose (DN) is not available. Symptoms range from the purely subjective sensation of a rather dry nose to visible crusting of the (inner) nose (nasal mucosa), and a wide range of combinations are met with. Relevant diseases are termed rhinitis sicca anterior, primary and secondary rhinitis atrophicans, rhinitis atrophicans with foetor (ozena), and empty nose syndrome. The diagnosis is based mainly on the patient's history, inspection of the external and inner nose, endoscopy of the nasal cavity (and paranasal sinuses) and the nasopharynx, with CT, allergy testing and microbiological swabs being performed where indicated. Treatment consists in the elimination of predisposing factors, moistening, removal of crusts, avoidance of injurious factors, care of the mucosa, treatment of infections and where applicable, correction of an over-large air space. Since the uncritical resection of the nasal turbinates is a significant and frequent factor in the genesis of dry nose, secondary RA and ENS, the inferior and middle turbinate should not be resected without adequate justification, and the simultaneous removal of both should not be done other than for a malignant condition. In this paper, we review both the aetiology and clinical presentation of the conditions associated with the symptom dry nose, and its conservative and surgical management.

Endonasal endoscopic medial maxillectomy with preservation of the inferior turbinate.

BACKGROUND: Endonasal endoscopic medial maxillectomy usually includes removal of the inferior turbinate (IT) even if it is not involved in the disease. A surgical approach is presented in which the IT is temporarily excised and then reinserted, followed by postoperative occlusion of the nose for at least 2 weeks. METHODS: A retrospective case series of 12 patients with inverted papilloma (IP) of the maxillary sinus (Krouse II-III) and 2 patients with 3 mucoceles of the maxillary sinus after a Caldwell-Luc operation were reviewed. After a follow-up period of 12-80 months (28 months on average) all patients underwent endoscopy, and in four cases, additionally, an MRI was performed. RESULTS: There was no recurrence of tumor or mucocele after 12-80 months. The IT and its important function for warming and humidifying the inhaled air could be preserved up to now in all 15 operated sides. The patients did not have any specific pain postoperatively and there was no postoperative bleeding. They all tolerated occlusion for 2-4 weeks. Two patients developed mucoceles due to the formation of scar tissue after endonasal tumor surgery. In three cases of endonasal endoscopic Denker operation patients reported some degree of numbness or irritation of the ipsilateral frontal teeth. CONCLUSION: The IT can be preserved in endonasal endoscopic medial maxillectomy for treatment of IP without a higher incidence of tumor recurrence. Aftercare should specifically focus on preventing the development of mucoceles caused by scarring.

Nasal packing and stenting.

Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue.

Evidence of psychosomatic influences in compensated and decompensated tinnitus.

The purpose of this study was to evaluate the role and interaction of individual factors on decompensated tinnitus. Subjects consisted of 53 adult patients with chronic tinnitus. They were selected and assigned to two groups, compensated (n = 28) and decompensated (n = 25), according to the results of an established tinnitus questionnaire. Both groups were evaluated and compared. The patients with decompensated tinnitus suffered from more pronounced social disabilities, were more prone to depression, and used less effective techniques to cope with their illness. They showed a higher degree of somatic multimorbidity, with particularly strong correlations between tinnitus and the incidence of cardiovascular diseases and hypoacusis. As a consequence, in the psychosomatic tinnitus therapy, greater attention should be given to the treatment of the somatic complaints in addition to psychological and psychosocial aspects.

Use of sodium fluorescein solution for detection of cerebrospinal fluid fistulas: an analysis of 420 administrations and reported complications in Europe and the United States.

BACKGROUND: Localization of dural fistulas in the region of the anterior or lateral skull base may be difficult. For many years, a sodium fluorescein solution of 0.5 to 5% (2.5-50 mg) has been administered intrathecally by way of the lumbar space. However, fluorescein is not commercially available for this stated purpose in either Germany or the United States. METHODS: Retrospectively, 420 fluorescein applications by the authors were retrospectively analyzed. Under the Freedom of Information Act, the United States Federal Drug Administration and the manufactures of fluorescein were queried for adverse reaction reports. RESULTS: Four hundred twenty fluorescein applications in 305 patients could be evaluated. Mean age of recipients was 46.9 years, ranging from 1 to 82 years. At a concentration of 5% fluorescein, 26 patients on the day of surgery and 69, 37, 34, and 14 patients on days 2 through 4 suffered from minor side effects that may or may not have been related to this drug. Two of these patients had grand mal seizures, which were attributable to simultaneous intrathecal application of contrast medium. All other side effects were thought to be the result of a postspinal headache and related lumbar puncture. At a concentration of 0.5%, the intraoperative intrathecal administration of 0.5 to 2 mL of fluorescein followed by 4 to 5 days of lumbar drainage resulted in some degree of spinal headache without other complications. In both groups, no patient had sequelae longer than 4 weeks. An additional seven complications were reported to the Federal Drug Administration and the fluorescein manufacturers at doses of 100 to 700 mg. CONCLUSIONS: Complications from intrathecal application of fluorescein appears to be dose dependent. At concentrations of 5%, or preferably lower, side effects are transient. A grand mal seizure can be minimized when following the general cautions of lumbar puncture and dose. The patient should be supervised for 24 hours. A written informed consent from patients for use of fluorescein is recommended.

[Psychosomatic stress factors in compensated and decompensated tinnitus]. / Psychosomatische Belastungsfaktoren bei kompensiertem und dekompensiertem Tinnitus.

AIMS: In modern medical practice, chronic decompensated tinnitus is defined as a complex psychosomatic process in which mental and social factors are considered to have a determining effect on the patient's subjective response to the impairment of otological or other somatic functions attributed to tinnitus. What is still largely unknown is the interaction of the individual factors and their impact on the patient's ability to cope with tinnitus. The impact of psycho-social and somatic factors on the subjective experience of patients with compensated and decompensated tinnitus is evaluated. PATIENTS AND METHODS: 53 patients with chronic tinnitus were divided into two groups, compensated and decompensated, on the basis of their subjective experience of the disorder, established according to the tinnitus questionnaire published by Goebel and Hiller. Self-assessment instruments and a survey of symptoms of somatic stress disorders were used to compare the two groups in terms of differences in the patients' mental and psycho-social behaviour, in their strategies for coping with tinnitus and in the incidence of co-morbidity. RESULTS: The patients with decompensated tinnitus suffered from more pronounced mental and social disabilities, were more prone to depression and used less effective techniques to cope with their illness. The principal difference between the two groups, however, appeared to lie in a significantly higher degree of somatic multi-morbidity, where a particularly strong correlation was found between tinnitus and the incidence of cardiovascular diseases and hypacusis. 81 percent of the total sample of patients suffered from impaired hearing. Patients with decompensated tinnitus experienced greater communication difficulties as a result of their auditory impairment. CONCLUSIONS: In the diagnosis and therapy of tinnitus, in addition to psychic and psycho-social aspects greater attention ought to be paid to somatic factors, influencing the patient's ability to cope with the disorder.