Mikkel Christian Alanin

Waiting times for diagnosis and treatment of head and neck cancer in Denmark in 2010 compared to 1992 and 2002

BACKGROUND AND AIM Significant tumour progression was observed during waiting time for treatment of head and neck cancer. To reduce waiting times, a Danish national policy of fast track accelerated clinical pathways was introduced in 2007. This study describes changes in waiting time and the potential influence of fast track by comparing waiting times in 2010 to 2002 and 1992. METHODS Charts of all new patients diagnosed with squamous cell carcinoma of the oral cavity, pharynx and larynx at the five Danish head and neck oncology centres from January to April 2010 (n=253) were reviewed and compared to similar data from 2002 (n=211) and 1992 (n=168). RESULTS The median time to diagnosis was 13 days (2010) versus 17 days (2002; p<0.001) and 20 days (1992; p<0.001). Median days from diagnosis to treatment start were 25 (2010) versus 47 (2002; p<0.001) and 31 (1992; p<0.001). Total pre-treatment time was median 41 days in 2010 versus 69 days (2002) (p<0.001) and 50 days (1992; p<0.001). Significantly more diagnostic imaging was done in 2010 compared to 2002 and 1992. When compared to current fast track standards the adherence to diagnosis improved slightly from 47% (1992) to 51% (2002) and 64% (2010); waiting time for radiotherapy was within standards for 7%, 1% and 22% of cases, respectively; waiting time for surgery was within standards for 17%, 22% and 48%, respectively. CONCLUSION The study showed a significant reduction in delay of diagnosis and treatment of head and neck cancer in 2010, but still less than half of all patients start treatment within the current standards.

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

Abstract 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.

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

Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs.

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.

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.

Clinical care of children with primary ciliary dyskinesia

ABSTRACT 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.

Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia: A systematic review.

Background A correlation exists between the microbial flora of the upper and lower airways in patients with cystic fibrosis (CF) or with primary ciliary dyskinesia (PCD). The sinuses can function as a bacterial reservoir where gram-negative bacteria adapt to the airways and repeatedly are aspirated to and colonize the lungs according to the theory of the united (unified) airways. Whereas the pattern of bacterial flora in the lower airways has been extensively studied, the upper airways have drawn limited attention. Objective Our aim was to review the literature that reported bacterial flora in the sinuses and nasal cavities of patients with CF or PCD. Methods A number of medical literature data bases were systematically searched between January 1960 and July 2016. We applied the following inclusion criteria: a minimum of one case of PCD (or Kartagener syndrome) or CF, and microbiology analyses from the nose or paranasal sinuses. Results We included 46 studies (1823 patients) from 16 countries. Staphylococcus aureus was found in 30% of the noses and sinuses of patients with CF. Other common bacteria found included Pseudomonas aeruginosa, coagulase negative staphylococci, and Haemophilus influenzae. In PCD, H. influenzae was the most common bacteria (28%), followed by Streptococcus pneumoniae and P. aeruginosa. If studies that included nonsurgical swab and blowing samples were excluded, then P. aeruginosa was the most common bacterium in patients with CF (34%) and in patients with PCD (50%), followed by S. aureus and H. influenza. Conclusion S. aureus, P. aeruginosa, coagulase negative staphylococci, and H. influenzae dominated in the upper airways of patients with CF. In patients with PCD, H. influenzae, S. pneumoniae, and P. aeruginosa dominated. When studies that included swab and blowing samples were excluded, P. aeruginosa was the most common bacterium in both groups. Direct comparisons among the studies were restricted due to very heterogeneous methods, and a better standardization of procedures and outcomes is needed.

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

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.

Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting.