Effect of Functional Endoscopic Sinus Surgery on Outcomes in Chronic Rhinosinusitis​.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) has a significant negative impact on quality of life (QoL). Surgical treatment of CRS is indicated when medical therapy fails to achieve adequate symptom control. This review summarizes the latest information on the outcomes after endoscopic sinus surgery (ESS) with relation to QoL, revision rates, olfaction, absenteeism, asthma control, use of systemic medications, quality of sleep and complications. We also provide an update regarding the factors that can impact outcomes. RECENT FINDINGS: CRS has classically been divided into two phenotypes depending on the presence or absence of nasal polyps. However, this is an oversimplification as many factors impact disease burden and outcome after treatment. It has been demonstrated that in many cases, ESS fails to meet the expectations of the patients. Evidence based patient counselling is key to help surgeons guide their patients in the best possible way to make well-informed decisions. Repeatedly it has been demonstrated that ESS improves QoL, improves olfaction, leads to better asthma control and less use of systemic antibiotics. However, various patient characteristics including phenotype, disease burden, comorbidities, age, gender and surgical technique can influence the outcome after ESSIt is of paramount importance to include a follow-up period when discussing revision rates. Based on available data, the genuine revision rate is probably 15-20% after five to ten years of follow-up. The revision rate is also affected by various factors and comorbidities.

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series.

PURPOSE: The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2-related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. MATERIALS AND METHODS: We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. RESULTS: The median duration of therapy was 27 months (range 16-34) and 42 MR scans (median 8, range 4-11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range -4%-+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was -10% (range -3%--25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. CONCLUSIONS: Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects.

The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2.

The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS) and severe hearing loss is common in NF2 patients. Vascular endothelial growth factor (VEGF) expression level in NF2 correlates with tumour growth rate and bevacizumab, a VEGF-binding antibody, has previously been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg/kg was administered every third week. Patients were evaluated with repeated audiometries, MR scans and clinical evaluations. Radiological response was defined as a 20 % or greater reduction in VS volume. A total of 398 treatments (median 36) were administered and the median duration on therapy was 22 months (range 7-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported subjective benefit in neurological symptoms, including improved hearing. Toxicity was in general manageable; however, one patient died from cerebral haemorrhage which was possibly related to therapy. In conclusion, bevacizumab improved hearing and reduced the size of VS in some patients with progressive NF2 which corroborates previous findings; however, the risk of severe side effects should be carefully considered and discussed with the patients prior to treatment.

[Traumatic orbitalt compartment syndrome].

Increased pressure in the orbital compartment is a medical emergency requiring immediate surgical intervention. Treatment should be initiated within the first hour to avoid permanent visual loss. This review describes the findings of orbital compartment syndrome and the procedure of performing lateral canthotomy and cantholysis. We recommend that any doctor seeing patients in an emergency setting should have knowledge of the symptoms and procedure.

[Chronic rhinosinusitisand type 2 disease].

Diseases of the upper and lower airways are commonly described as global airway disease, which shares basic inflammatory mechanisms, and airway comobidity is frequently found. The prevalence of chronic rhinosinusitis (CRS) is 5-12%, characterised as CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). Inflammation in CRSwNP is often type 2, whereas CRSsNP often involves non-type 2. New monoclonal antibodies towards type-2 inflammation have been launched internationally to treat refractory severe CRSwNP, with effect on polyps, congestions and smell, as well as quality of life. This review gives a summary of the current treatment modalities.

[Traumatic orbital compartment syndrome].

Orbital compartment syndrome is an uncommon complication of trauma to the eye and its surroundings or a rare complication to sinus surgery. Nevertheless, it is important to diagnose and treat the condition urgently as it may cause irreversible visual impairment. In this case report, we describe a 29-year-old male suffering from a blunt trauma to the eye. He developed exophthalmus and visual impairment. A blow-out fracture and haematoma in the orbital compartment was diagnosed. Successful bedside urgent lateral canthotomy and cantholysis was performed followed by semi-urgent osteosynthesis of the fracture. The patient recovered without visual impairment.

Chronic rhinosinusitis in COPD: A prevalent but unrecognized comorbidity impacting health related quality of life.

INTRODUCTION: Unified airway disease where upper respiratory tract inflammation including chronic rhinosinusitis (CRS) affects lower airway disease is known from asthma, bronchiectasis, cystic fibrosis and primary ciliary dyskinesia but little is known about CRS and health related quality of life in COPD. We investigate firstly, the prevalence of CRS in COPD. Secondly the impact of CRS on HRQoL. Thirdly, risk factors for CRS in COPD. METHODS: cross-sectional study of CRS in 222 COPD patients from 2017 to 2019 according to EPOS2012/2020 and GOLD2019 criteria. Patients completed the COPD assessment test (CAT), Medical Research Council dyspnea scale and Sinonasal outcome test 22 (SNOT22) and questions on CRS symptoms. They then had a physical examination including flexible nasal endoscopy, CT-sinus scan and HRCT-thorax. RESULTS: 22.5% of COPD patients had CRS and 82% of these were undiagnosed prior to the study. HRQoL (CAT, SNOT22 and the SNOT22-nasal symptom subscore) was significantly worse in COPD patients with CRS compared with those without CRS and healthy controls. Multiple logistic regression analysis suggests that the most likely candidate for having CRS was a male COPD patient who actively smoked, took inhaled steroids, had a high CAT and SNOT22_nasal symptom subscore. DISCUSSION: the largest clinical study of CRS in COPD and the only study diagnosing CRS according to EPOS and GOLD. This study supports unified airway disease in COPD. The SNOT22_nasal symptoms subscore is recommended as a standard questionnaire for COPD patients and patients at risk should be referred to an otorhinolaryngologist.

[The cardiovocal syndrome].

Ortner's syndrome, also known as the cardiovocal syndrome, refers to left recurrent laryngeal nerve palsy and hereby hoarseness due to cardiovascular disease. The palsy arises from compression of the nerve, as it passes between the aortic arch and the pulmonary artery. This case report describes a patient, who presented with hoarseness and recurrent laryngeal nerve palsy due to an 8 × 7.3 cm thoracic aortic aneurism, and it shows the importance of including cardiovascular diseases in the differential diagnosis of hoarseness in patients with cardiovascular risk factors.

Can secretory immunoglobulin A in saliva predict a change in lung infection status in patients with cystic fibrosis? A prospective pilot study.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is the main cause of mortality in patients with cystic fibrosis (CF). Sinus colonization with P. aeruginosa often precedes intermittent lung colonization, and intermittent colonization precedes chronic infection.When P. aeruginosa colonizes the sinuses, elevated immunoglobulin A (IgA) levels specific against P. aeruginosa can be detected in saliva. Therefore, we hypothesized that increasing levels of IgA in saliva can be detected before P. aeruginosa lung colonization. METHODS: Forty-nine CF patients free from lung colonization with P. aeruginosa or other Gram-negative bacteria (GNB) were included in this prospective study. Saliva and serum samples were collected and examined for IgA antibodies against P. aeruginosa with at least 6-month intervals between sequential samples. RESULTS: A total of 110 measurements of IgA in saliva were included. During a median of 8.5-month follow-up, 25 patients changed their lung infection status. We were able to construct a statistical model that for a given value of IgA in saliva, could predict the probability of a change in lung infection status within the next 8.5 months (median): p = 1 / (1 + exp(-(-0.9582 + 1.6518*IgA)). The model includes a prediction band where 95% of new measurements are predicted to fall within. The model, however, failed to reach statistical significance (P = 0.056 1-tailed), probably because of lack of power. CONCLUSION: The saliva IgA model may predict a worsening in lung infection status presumably acting as a surrogate marker of P. aeruginosa bacterial sinusitis. The model may identify patients at risk of subsequent lung colonization and, thus, be a helpful clinical tool, but it should be tested in studies with larger sample sizes to evaluate its utility.

Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia: adressing the paranasal sinuses.

The respiratory tract is lined with motile cilia that transport respiratory mucus. Primary ciliary dyskinesia (PCD) is a chronic genetic disease caused by mutations in genes responsible for ciliary structure and function. Non-functional airway cilia impair the mucociliary clearance (MCC), causing mucostasis, lung infections and destruction, chronic rhinosinusitis (CRS) and hearing impairment. It is of paramount importance to postpone chronic lung infection mainly with Gram-negative bacteria (GNB) in patients with an impaired MCC. When successful, lung function can be stabilized and quality of life (QoL) improved. In this thesis, we evaluated whether PCD patients can benefit from the experience we have gained from our operative approach towards the paranasal sinuses in cystic fibrosis (CF) patients. In CF, it has been established that bacterial sinusitis can be a focus for initial lung colonization and chronic lung infection. Combined endoscopic sinus surgery (ESS) and adjuvant therapy can eradicate sinus bacteria, reduce pulmonary infections and improve quality of life (QoL).      Currently, approximately 120 patients are diagnosed with PCD in Denmark and all are affiliated with the Danish PCD Centre. Patients included in this thesis were recruited from this cohort. In papers (I, IV), we found that the most frequent sinus pathogen was P. aeruginosa, which was isolated in 12 out of 31 (39%) patients who underwent ESS. In searching for a non-pulmonary infectious focus, we observed simultaneous sinus and lung infec-tions with identical pathogens in two out of three patients. This supports our hypothesis of a bacterial reservoir in the sinuses. Next (II), we examined the bacterial flora associated with acute and chronic pulmonary infections in PCD. A high prevalence of chronic infections encouraged a search for new treatment regimens, including ESS with adjuvant therapy, to impact the course of infection. We revealed that P. aeruginosa frequently colonizes the airways in PCD and during the 11-year study period a total of 42 out of 107 (39%) patients fulfilled the definition of chronic lung infection at some point. Importantly, 10 out of 12 patients (83%) with chronic lung infection had the same clone type of P. aeruginosa for years, as determined by pulsed field gel-electrophoresis (PFGE), thus substantiating factual chronic airway infection. Further, we found an increase in the prevalence of P. aeruginosa with age and observed a negative association between early PCD diagnosis and prevalence of P. aeruginosa. This indicates a positive effect of early diagnosis and initiation of therapy. In paper (III), we performed whole genome sequencing (WGS) of P. aeruginosa isolated from the same 12 patients who were included in the PFGE analysis in paper II. By sequencing and phenotypically characterizing multiple isolates from the same patients we were able to study the with-in host bacterial evolution for the first time in PCD. The analyses provided detailed insight into how P. aeruginosa evolves in PCD when they are stressed by the host immune system and antibiotics. We verified the persistence of clonal lineages and confirmed that different clone types of P. aeruginosa can establish persistent infections in PCD patients. Further, we showed that P. aeruginosa acclimatizes grad-ually to the PCD airway by accumulating pathoadaptive mutations and phenotypic characteristics similar to those of CF. Such information may provide valuable clinical information, and as an example we identified mutations in genes responsible for the development of antibiotic resistance. Based on our research we conclude that P. aeruginosa is a major pathogen in PCD and that future research should focus on pre-venting or eradicating these bacteria. Implementing ESS with adjuvant therapy to PCD patients (I, IV) significantly ameliorated CRS symptoms. Further, postoperatively patients tended to have fewer positive lower airway cultures and better lung function; approximately one out of four operated patients, in search of an infectious focus, remained free of lung colonization with P. aeruginosa during follow-up for at least six months. Based on these results, it is tempting to speculate that ESS with adjuvant therapy can eradicate sinus bacteria and thereby reduce lung re-colonization from the sinuses. However, further evidence is needed to support this hypothesis, preferably from a multicentre randomized controlled trial.

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia.

BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics. Additional treatment with local colistin for 6 months was instigated when P. aeruginosa was cultured at ESS. RESULTS: Twenty-four PCD patients underwent ESS to search for an infectious focus (n = 10), due to severe symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus samples in 21 patients (88%), and simultaneous sinus and lung colonization with identical pathogens were observed in 13 patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. CONCLUSION: We demonstrated an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function.

Clinical care of children with primary ciliary dyskinesia.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disorder, usually inherited as an autosomal recessive condition but X-linked inheritance is also described. Abnormal ciliary function in childhood leads to neonatal respiratory distress in term infants, persistent wet cough, bronchiectasis, chronic rhinosinusitis, and hearing impairment; approximately 50% of patients have situs inversus. There is a paucity of evidence for treating PCD, hence consensus guidelines are predominantly influenced by knowledge from cystic fibrosis (CF). Extrapolation of evidence from other diseases is inappropriate since differences in pathophysiology, morbidity and prognosis risk treatment failure and lack of adherence. Areas covered: Review authors searched PubMed and Cochrane databases for publications relating to management of children with PCD. Because of the paucity of data, we emphasise the need for well-designed clinical trials with PCD patients rather than reliance on evidence from other diseases. Expert commentary: The evidence for treatment of PCD is poor, and management is often extrapolated from studies of patients with CF or chronic rhinosinusitis. However, much work is underway to improve the situation and international consortia and networks are conducting well-designed projects to inform the management of children with PCD.

A longitudinal evaluation of hearing and ventilation tube insertion in patients with primary ciliary dyskinesia.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disease, which primarily manifests with oto-sino-pulmonary symptoms. Otitis media with effusion (OME) is common from early childhood. The existing literature on OME management in PCD is conflicting. The goals of the present study were firstly to evaluate the long-term hearing in PCD patients and secondly to determine the influence of ventilation tube (VT) insertion on hearing and postoperative otorrhoea. METHODS: A longitudinal retrospective study extracting the hearing level (pure tone average (0.5, 1, 2, 4 kHz, PTA)) and tympanometry from the medical records. Furthermore, the patient files were reviewed for VT insertion and postoperative otorrhoea. Postoperative otorrhoea was defined prolonged when it lasted for four weeks or longer. RESULTS: Fifty-seven patients were identified in a 30-year period, age 2-72 years, and 278 audiometries were evaluated. The median number of audiometries per patient was 3 (range 1-29) and the median follow-up was 60 months (range 0-351 months). The mean PTA was 34 dB HL in patients below six years of age and improved significantly (p < 0.0001) with age. VT insertion improved hearing; however, 48% of patients with VT insertion experienced prolonged otorrhoea. CONCLUSION: In this study of PCD patients the hearing improved as a function of age as well as following VT insertion. However, VT insertion was also associated with prolonged otorrhoea.

Bacterial evolution in PCD and CF patients follows the same mutational steps.

Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.

Simultaneous sinus and lung infections in patients with primary ciliary dyskinesia.

CONCLUSION: The sinuses should be considered as a bacterial reservoir and a target for surgery and antibiotic treatment in patients with primary ciliary dyskinesia (PCD). The observed decrease in serum precipitating antibodies (precipitins) against Pseudomonas aeruginosa may indicate a beneficial effect of combined endoscopic sinus surgery (ESS) and concomitant medical treatment. OBJECTIVES: The purpose of this research, which is the first study addressing bacteriology in the sinuses of patients with PCD, was to examine the association between sinus and lung infections. METHODS: We reviewed findings of bacterial pathogens from the sinuses obtained during ESS and the lung infection status in eight PCD patients over a 6 year period. Precipitins against P. aeruginosa were used as a marker of severity of chronic infection and effect of treatment. RESULTS: Preoperatively, seven of the eight patients (88%) exhibited intermittent or chronic pulmonary infection with P. aeruginosa. Sinus cultures were obtained during ESS in seven patients. The sinuses were colonized with P. aeruginosa in four of seven patients (57%). Bacterial sinusitis was found in five of seven patients (71%) and the same bacterium was found in the sinuses and lungs in all cases. Decreasing precipitins against P. aeruginosa were observed postoperatively in three of four evaluable patients.

[Metastasizing esthesioneuroblastoma]. / Metastaserende estesioneuroblastom.

Esthesioneuroblastoma is a rare malignant tumour that originates from the olfactory region. Its incidence is about 0.4 per million per year. The most common symptoms include epistaxis, headache, nasal obstruction, hyposmia and eye symptoms. Diagnosis of this rare tumour is often delayed. We present a case in which a 61-year-old male was referred due to proptosis and loss of vision. Magnetic resonance imaging showed a tumour in the nasal cavity involving the orbit, the frontal lope of the brain and lymph nodes in the neck. The case was staged according to Kadish as a stage C. Surgery was performed and postoperative radiotherapy planned.

[Blindness due to acute ethmoiditis]. / Akut etmoiditis kan medføre blindhed.

Orbital complications of ethmoiditis are well-described. This case presents a healthy ten-year-old boy who was admitted under the diagnosis of acute ethmoiditis. A computed tomography (CT) showed orbital cellulitis, but no definite abscess. The patient improved during intravenous antibiotic treatment, but suddenly complained about loss of vision. The clinical signs were central scotoma and visual impairment to 0.05. Both repeat CT, magnetic resonance imaging and ethmoidectomy were performed without signs of abscess. Blindness due to ethmoiditis without abscess in orbita is rare and probably results from neuritis in the nervus opticus.