Publications by authors named "Markus Rautiainen"

57 Publications

Effect of pulse waveforms on movement amplitudes and perceived discomfort in electric muscle stimulation in unresolved facial nerve palsy.

Biomed Phys Eng Express 2020 03 25;6(3):035013. Epub 2020 Mar 25.

Department of Clinical Neurophysiology, Medical Imaging Centre, Pirkanmaa Hospital District, PO Box 2000, 33521 Tampere, Finland. Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33014, Tampere, Finland.

Studies on the effects of the pulse waveform used in electrical muscle stimulation on the activations and perceived discomfort of the waveform have been mainly executed on limb muscles with variable results, however, knowledge of these effects on facial muscles is currently lacking. We studied two waveforms, square wave and sinusoidal wavelet, for the activation of the frontalis muscle in 9 individuals with unresolved facial nerve palsy. Both waveforms produced a movement that was greater in amplitude compared with the maximal voluntary movement of the affected side in 8 participants and at least as great as the healthy side's maximal voluntary movement in 4 participants. Both waveforms were equally successful in producing movements, and there was no significant difference in perceived discomfort ratings between the two waveforms. These findings will be useful for the future development of neuroprosthetic applications for reanimating facial muscles using electrical stimulation. Trial registration: ClinicalTrials.gov NCT03496025, registration date March 19, 2018.
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http://dx.doi.org/10.1088/2057-1976/ab7eeaDOI Listing
March 2020

The expression and prognostic relevance of programmed cell death protein 1 in tongue squamous cell carcinoma.

APMIS 2020 Dec 19;128(12):626-636. Epub 2020 Oct 19.

Haartman Institute, University of Helsinki, Helsinki, Finland.

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor which plays an important role in a patient's immune responses to microbial and cancer antigens. It is expressed in tumor-infiltrating lymphocytes (TILs) with many different malignancies. The aim of the study was to evaluate PD-1 expression and its prognostic value in tongue cancer. The data of tongue squamous cell carcinoma (TSCC) patients (N = 81) treated in Tampere University Hospital between 1999 and 2013 were used. Control data consisted of patients with non-malignant tongue mucous membrane lesions (N = 48). The formalin-fixed paraffin-embedded samples were stained immunohistochemically and scanned via digital microscope. The staining of PD-1 was examined semi-quantitatively. The density and intensity of PD-1 + cells were significantly higher in TSCC than in control samples. The expression of PD-1 correlated with better survival. The expression of PD-1 could be a potential prognostic marker in TSCC. Further research using larger sample size is needed.
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http://dx.doi.org/10.1111/apm.13084DOI Listing
December 2020

Assessment of PIV performance in validating CFD models from nasal cavity CBCT scans.

Respir Physiol Neurobiol 2020 11 30;282:103508. Epub 2020 Jul 30.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Otorhinolaryngology - Head and Neck Surgery, Tampere University Hospital, Tampere, Finland.

Objective: The aim of our study was to investigate how well Particle Image Velocimetry (PIV) measurements could serve Computational Fluid Dynamics (CFD) model validation for nasal airflow.

Material And Methods: For the PIV measurements, a silicone model of the nose based on cone beam computed tomography (CBCT) scans of a patient was made. Corresponding CFD calculations were conducted with laminar and two turbulent models (k-ω and k-ω SST).

Results: CFD and PIV results corresponded well in our study. Especially, the correspondence of CFD calculations between the laminar and turbulent models was found to be even stronger. When comparing CFD with PIV, we found that the results were most convergent in the wider parts of the nasal cavities.

Conclusion: PIV measurements in realistically modelled nasal cavities succeed acceptably and CFD calculations produce corresponding results with PIV measurements. Greater model scaling is, however, necessary for better validations with PIV and comparisons of competing CFD models.
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http://dx.doi.org/10.1016/j.resp.2020.103508DOI Listing
November 2020

Snoring toddlers with and without obstructive sleep apnoea differed with regard to snoring time, adenoid size and mouth breathing.

Acta Paediatr 2021 Mar 21;110(3):977-984. Epub 2020 Aug 21.

Department of Paediatrics, Tampere University Hospital, Tampere, Finland.

Aim: The difficulty of assessing the likelihood of obstructive sleep apnoea (OSA) in children who snore without full-night polysomnography is widely recognised. Our aim was to identify features that were characteristic of two-year-old children with OSA and evaluate whether this information could be used to assess the likelihood of OSA.

Methods: The study was carried out as part of the Child-Sleep Project, a longitudinal birth cohort study of children born at Tampere University Hospital, Finland. This part of the study focused on the children in the cohort who snored and was carried out between 2013 and 2015. The primary outcomes were measured using parental questionnaires, polysomnography and clinical examinations.

Results: In total, 52 children participated at a mean age of 27 months (range 23-34). Of these, 32 (44% male) snorers and 20 (70% male) controls. The most significant findings were that children who had OSA demonstrated longer snoring time (P = .003), a greater tendency for mouth breathing (P = .007) and bigger adenoid size (P = .008) than snorers without OSA.

Conclusion: Snoring time, adenoid tissue size and mouth breathing were important features that identified the likelihood of OSA in snoring toddlers.
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http://dx.doi.org/10.1111/apa.15496DOI Listing
March 2021

Is securing normal dentofacial development an indication for tonsil surgery in children? A systematic review and meta-analysis.

Int J Pediatr Otorhinolaryngol 2020 Jun 18;133:110006. Epub 2020 Mar 18.

Department of Ear and Oral Diseases, Tampere University Hospital, SKS/TAYS PL 2000 33521, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Institute of Dentistry, University of Eastern Finland, Kuopio, Finland. Electronic address:

Objective: Tonsil surgeries are common operations in the field of paediatric otorhinolaryngology. Often, the indication for these operations is hypertrophied tonsils. Paediatric sleep-disordered breathing and mouth-breathing are conventional situations caused by the hypertrophied tonsils. Both of these are further associated with dentofacial development alterations. Securing normal dentofacial development, or restoring it, is often used as an indication for tonsil surgery. In this review and meta-analysis, we assessed the contemporary literature to clarify whether tonsil surgery has an effect on dentofacial development in children.

Methods: Studies with children aged 3-10 years who underwent tonsil surgery and were compared to non-operated controls using dentofacial parameters were included to the review. Search strategies were planned for specific databases. The Newcastle-Ottawa scale was used to assess the risk of bias. A meta-analysis was performed when the data was methodologically homogenous enough to be pooled.

Results: The inclusion criteria for the review were fulfilled in 8 studies. The overall quality of the individual studies was judged to be moderate at best. The data were methodologically homogenous enough to be pooled for the meta-analysis in only 2 studies. The results of the meta-analysis revealed that tonsil surgery has a positive effect on the growth direction of the mandible (p < 0.001).

Conclusions: There is modest evidence that suggests that tonsil surgery has a positive effect on the dentofacial development in children with hypertrophied tonsils. Securing normal dentofacial development should be one component, but not the only one, when the indications for tonsil surgery in children are considered.
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http://dx.doi.org/10.1016/j.ijporl.2020.110006DOI Listing
June 2020

Ethmoidal drug-eluting stent therapy is not superior to nasal corticosteroid spray in the prevention of endoscopic sinus surgery: Results from a randomised, clinical trial.

Clin Otolaryngol 2020 05 10;45(3):402-408. Epub 2020 Mar 10.

Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.

Objectives: To evaluate whether an ethmoidal drug-eluting stent (DES) (the Relieva Stratus™ MicroFlow Spacer) could better prevent endoscopic sinus surgery (ESS) than standard non-invasive therapy using corticosteroid nasal spray in patients suffering from chronic rhinosinusitis (CRS).

Design: Prospective, randomised clinical trial.

Setting: Tertiary referral centre.

Participants: Sixty-three adult patients with ethmoidal involvement in cone beam computerised tomography (CBCT) whose first-line medical treatment with topical corticosteroids had failed and who were candidates for ESS were randomised either to a DES group, which received triamcinolone acetonide stents (n = 34), or to a topical intranasal corticosteroid group (n = 29) that used optimally dosed triamcinolone acetonide nasal spray.

Outcome Measures: Patients were followed up prospectively for 6 months and at 36 months. Freedom from ESS was the primary endpoint. Further, we identified those factors predicting ESS.

Results: At 6 months, ESS could be prevented in almost half of the patients in both groups (DES 13/28, 46.4%, nasal spray 14/29, 48.3%). At 36 months, 20/28 (71.4%) patients in the DES group and 18/29 (62.1%) in the nasal spray group had been operated. The differences were not statistically significant at either timepoint. Patients who smoked (14/19, 73.7% vs 16/38, 42.1%) were more likely to be operated at 6 months.

Conclusion: Endoscopic sinus surgery can be prevented using both therapies in the medium term in almost half of cases with neither therapy being statistically superior. This effect was somewhat diminished in the long term with a trend towards more patients being operated in the DES group. Considering the additional costs, the need for general anaesthesia and the potential side effects associated with DES, its potential clinical role appears to be limited. Smoking was significantly associated with ESS.
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http://dx.doi.org/10.1111/coa.13515DOI Listing
May 2020

Three-Dimensional Printing of the Nasal Cavities for Clinical Experiments.

Sci Rep 2020 01 16;10(1):502. Epub 2020 Jan 16.

Department of Otorhinolaryngology - Head and Neck Surgery, Tampere University Hospital, Tampere, Finland.

3D printing has produced many beneficial applications for surgery. The technique´s applicability in replicating nasal cavity anatomy for clinical use has not been studied. Our aim was to determine whether 3D printing could realistically replicate the nasal cavities and the airflow passing through them from a clinical point of view. We included Cone Beam Computed Tomography (CBCT) scans of five patients with symptoms of chronic nasal congestion. These CBCT scans were used to print plastic 3D prints of the nasal cavities, which were also CBCT scanned and the measurements were compared. The results in vivo were higher than the results in vitro in maxillary sinus volumes with a ratio of 1.05 ± 0.01 (mean ± SD) and in the nasal cavities with a ratio of 1.20 ± 0.1 (mean ± SD). Linear measurements in vitro were very close to those in vivo. Rhinomanometric results showed some differences, but rhinomanometric graphs in vitro were close to the graphs in vivo. 3D printing proved to be a suitable and fast method for replicating nasal cavity structures and for the experimental testing of nasal function. It can be used as a complementary examination tool for rhinomanometry.
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http://dx.doi.org/10.1038/s41598-020-57537-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965131PMC
January 2020

Association between snoring and deciduous dental development and soft tissue profile in 3-year-old children.

Am J Orthod Dentofacial Orthop 2019 Dec;156(6):840-845

Department of Ear and Oral Diseases, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Institute of Dentistry, University of Eastern Finland, Kuopio, Finland. Electronic address:

Introduction: The aim was to study the association between snoring and development of occlusion, maxillary dental arch, and soft tissue profile in children with newly completed deciduous dentition.

Methods: Thirty-two (18 female, 14 male) parent-reported snorers (snoring ≥3 nights/week) and 19 (14 female, 6 male) nonsnorers were recruited. Breathing preference (nose or mouth) was assessed at the mean age of 27 months by otorhinolaryngologist. At the mean age of 33 months, an orthodontic examination was performed, including sagittal relationship of second deciduous molars, overjet, overbite, and occurrence of crowding and lateral crossbite. Bite index was obtained to measure maxillary dental arch dimensions (intercanine and intermolar width, arch length). A profile photograph was obtained to measure facial convexity.

Results: No significant differences were found between nonsnorers and snorers in any of the studied occlusal characteristics or in measurements of maxillary dental arch dimensions. Snorers were found to have a more convex profile than nonsnorers. Occurrence of mouth breathing was more common among snorers.

Conclusions: Parent-reported snoring (≥3 nights/week) does not seem to be associated with an adverse effect on the early development of deciduous dentition, but snoring children seem to have more convex profile than nonsnorers. Snoring is a mild sign of sleep-disordered breathing, and in the present study its short time lapse may not have had adequate functional impact on occlusion.
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http://dx.doi.org/10.1016/j.ajodo.2019.02.015DOI Listing
December 2019

Facial muscle reanimation by transcutaneous electrical stimulation for peripheral facial nerve palsy.

J Med Eng Technol 2019 Apr 15;43(3):155-164. Epub 2019 Jul 15.

b Faculty of Medicine and Health Technology, Tampere University , Tampere , Finland.

Reanimation of paralysed facial muscles by electrical stimulation has been studied extensively in animal models, but human studies in this field are largely lacking. Twenty-four subjects with a peripheral facial nerve palsy with a median duration of three years were enrolled. We studied activations of four facial muscles with electrical stimulation using surface electrodes. In subjects whose voluntary movement was severely impaired or completely absent, the electrical stimulation produced a movement that was greater in amplitude compared with the voluntary effort in 10 out of 18 subjects in the muscle, in 5 out of 14 subjects in the muscle, and in 3 out of 8 subjects in the muscle. The electrical stimulation produced a stronger blink in 8 subjects out of 22 compared with their spontaneous blinks. The stimulation could produce a better movement even in cases where the muscles were clinically completely paretic, sometimes also in palsies that were several years old, provided that the muscle was not totally denervated. Restoring the function of paralysed facial muscles by electrical stimulation has potential as a therapeutic option in cases where the muscle is clinically paretic but has reinnervation.
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http://dx.doi.org/10.1080/03091902.2019.1637470DOI Listing
April 2019

Craniofacial and occlusal development in 2.5-year-old children with obstructive sleep apnoea syndrome.

Eur J Orthod 2019 05;41(3):316-321

Department of Ear and Oral Diseases, Tampere University Hospital.

Objectives: Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with a range of changes in craniofacial and occlusal development. There is, however, little knowledge of how early in life these changes can be found. The aim of the present study was to determine whether changes in dental arch morphology, occlusion, facial profile, tonsil size, breathing habit or body mass index (BMI) can already be found among 2.5-year-old children with OSAS.

Materials And Methods: Fifty-two children were recruited to the study. Of these, OSAS was diagnosed in 9 children and 18 children did not snore in polysomnography. These two groups were subsequently compared when evaluating polysomnographic, otorhinolaryngological and dental variables.

Results: Children with OSAS had narrower inter canine width than non-snoring children (P = 0.032). Furthermore, children with OSAS had larger adenoid size with respect to the nasopharyngeal volume (P = 0.020) and more tendency to mouth breathing (P = 0.002). No statistically significant differences were found when comparing palatine tonsil size, occlusal characteristics, soft tissue profile measurements or BMI.

Limitations: The limitation of the study is the small sample size.

Conclusion: Children with OSAS had narrower upper inter canine width than non-snoring children at the age of 2.5 years. Larger adenoid size and mouth breathing tendency were also more common among children with OSAS. Further studies with larger sample sizes are needed to determine if other changes in craniofacial and occlusal development can be found in this age group.
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http://dx.doi.org/10.1093/ejo/cjz009DOI Listing
May 2019

Mucociliary function of the eustachian tube in the eustachian tube dysfunction.

Acta Otolaryngol 2019 Mar 14;139(3):238-242. Epub 2019 Mar 14.

a Department of Otorhinolaryngology, University of Tampere, Faculty of Medicine and Life Sciences, Tampere University Hospital , Tampere , Finland.

Background: Most of the tests to evaluate the eustachian tube (ET) function are focused on the ventilation function of the ET.

Aim: Here we evaluate mucociliary function of the ET in patients with ET dysfunction.

Materials And Methods: Ten patients with ET dysfunction were enrolled into the study. Six patients had chronic tympanic membrane retraction and four patients had chronic middle ear effusion (MEE). All patients had intact tympanic membranes. Tympanometry and clinical examinations were done to all patients. Mucociliary function was evaluated with technetium labeled albumin and blue dye. Tympanometry and clinical examinations were done to six patients with chronic tympanic membrane retraction and four patients with chronic middle ear effusion (MEE). Mucociliary function of the ET was evaluated with technetium labeled albumin and blue dye placed into middle ear through an intact tympanic membrane and followed from nasopharynx ET orifice (blue dye) and with gamma camera (technetium).

Results: Blue dye was observed in tubal orifice in six (6 of 10) patients during 30 min observation. Five of those patients (5 of 6) had tympanic membrane retraction and one patient (1 of 6) had MEE. Tracer activity decreased from middle ear in six (6 of 10) patients. Four of those patients had tympanic membrane retraction and two had MEE.

Conclusion: Mucociliary function of the ET seems to be better in patients with tympanic membrane retraction than patients with middle ear effusion.

Significance: Mucociliary function of the ET is an important function for middle ear aeration, blue dye test is easily available to be used also in clinical practice.
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http://dx.doi.org/10.1080/00016489.2018.1562218DOI Listing
March 2019

Three-Dimensional Volumetric Evaluation of the Maxillary Sinuses in Chronic Rhinosinusitis Surgery.

Ann Otol Rhinol Laryngol 2018 Dec 22;127(12):931-936. Epub 2018 Sep 22.

1 Department of Ear and Oral Diseases, Tampere University Hospital and Department of Otorhinolaryngology, University of Tampere, Tampere, Finland.

Introduction:: The objective of this study was to ascertain whether the 3-dimensional volumetric measurement method could be used for the evaluation of operative treatment results in patients with chronic rhinosinusitis.

Methods:: A total of 61 adult patients with chronic rhinosinusitis were analyzed. Cone-beam computed tomographic images of the paranasal sinuses were examined preoperatively and at 12 months postoperatively. The results were compared using the Sino-Nasal Outcome Test (SNOT-22) and the Lund-Mackay (LM) and Zinreich modified staging systems.

Results:: The mean change in pneumatized volumes in the maxillary sinuses after operative treatment per patient was 2.0 ± 7.5 cm ( P = .146). The median for volumetric change was 0.97 cm (range, -11.6 to 33.6 cm). Both the LM and Zinreich modified LM staging systems showed no change in 32 of 61 patients (53%). The alterations in patients' maxillary sinuses measured using the volumetric measurement method correlated well with changes in Zinreich's modified LM staging (-0.77, P < .01).

Conclusions:: The 3D volumetric method is more sensitive in detecting small alterations in pneumatized volumes of the maxillary sinuses than Zinreich's modified LM staging and LM staging. The method correlates better with Zinreich's modified LM staging than with LM staging.
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http://dx.doi.org/10.1177/0003489418801386DOI Listing
December 2018

The effect of inferior turbinate surgery on ciliated epithelium: A randomized, blinded study.

Laryngoscope 2019 01 27;129(1):18-24. Epub 2018 Aug 27.

Department of Otorhinolaryngology, Tampere University Hospital, Tampere, Finland.

Objectives/hypothesis: The aim of this study was to evaluate statistically the effects of radiofrequency ablation, diode laser, and microdebrider-assisted inferior turbinoplasty techniques on ciliated epithelium and mucociliary function.

Study Design: Prospective randomized study.

Methods: A total of 66 consecutively randomized adult patients with enlarged inferior turbinates underwent either a radiofrequency ablation, diode laser, or microdebrider-assisted inferior turbinoplasty procedure. Assessments were conducted prior to surgery and 3 months subsequent to the surgery. The effect on ciliated epithelium was evaluated using a score based on the blinded grading of the preoperative and postoperative scanning electron microscopy images of mucosal samples. The effect on mucociliary function, in turn, was evaluated using saccharin transit time measurement.

Results: The score of the number of cilia increased statistically significantly in the radiofrequency ablation (P = .03) and microdebrider-assisted inferior turbinoplasty (P = .04) groups, but not in the diode laser group. The score of the squamous metaplasia increased statistically significantly in the diode laser group (P = .002), but not in the other two groups. There were no significant changes found between the preoperative and postoperative saccharin transit time values in any of the treatment groups.

Conclusions: Radiofrequency ablation and microdebrider-assisted inferior turbinoplasty are more mucosal preserving techniques than the diode laser, which was found to increase the amount of squamous metaplasia at the 3-month follow-up. The number of cilia seemed to even increase after radiofrequency ablation and microdebrider-assisted inferior turbinoplasty procedures, but not after diode laser. Nevertheless, the mucociliary transport was equally preserved in all three groups.

Level Of Evidence: 1b Laryngoscope, 129:18-24, 2019.
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http://dx.doi.org/10.1002/lary.27409DOI Listing
January 2019

In vitro detection of common rhinosinusitis bacteria by the eNose utilising differential mobility spectrometry.

Eur Arch Otorhinolaryngol 2018 Sep 24;275(9):2273-2279. Epub 2018 Jul 24.

Department of Otorhinolaryngology, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University Hospital, PL 2000, 33521, Tampere, Finland.

Acute rhinosinusitis (ARS) is a sudden, symptomatic inflammation of the nasal and paranasal mucosa. It is usually caused by respiratory virus infection, but bacteria complicate for a small number of ARS patients. The differential diagnostics between viral and bacterial pathogens is difficult and currently no rapid methodology exists, so antibiotics are overprescribed. The electronic nose (eNose) has shown the ability to detect diseases from gas mixtures. Differential mobility spectrometry (DMS) is a next-generation device that can separate ions based on their different mobility in high and low electric fields. Five common rhinosinusitis bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa) were analysed in vitro with DMS. Classification was done using linear discriminant analysis (LDA) and k-nearest neighbour (KNN). The results were validated using leave-one-out cross-validation and separate train and test sets. With the latter, 77% of the bacteria were classified correctly with LDA. The comparative figure with KNN was 79%. In one train-test set, P. aeruginosa was excluded and the four most common ARS bacteria were analysed with LDA and KNN; the correct classification rate was 83 and 85%, respectively. DMS has shown its potential in detecting rhinosinusitis bacteria in vitro. The applicability of DMS needs to be studied with rhinosinusitis patients.
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http://dx.doi.org/10.1007/s00405-018-5055-8DOI Listing
September 2018

A prospective, randomized, placebo-controlled study of inferior turbinate surgery.

Laryngoscope 2018 09 2;128(9):1997-2003. Epub 2018 Feb 2.

Department of Otorhinolaryngology, Tampere University Hospital, Tampere, Finland.

Objectives/hypothesis: The purpose of this study was to compare radiofrequency ablation, diode laser, and microdebrider-assisted inferior turbinoplasty techniques in the treatment of chronic nasal obstruction caused by inferior turbinate enlargement, and to compare these techniques with a placebo procedure.

Study Design: Prospective, randomized, single-blinded, placebo-controlled study.

Methods: A total of 98 consecutive patients with enlarged inferior turbinates due to persistent year-round rhinitis were randomized into a placebo, radiofrequency ablation, diode laser, and microdebrider-assisted inferior turbinoplasty groups in a ratio of 1:2:2:2. All the procedures were carried out under local anesthesia with the patients' eyes covered. Assessments were conducted prior to surgery and 3 months subsequent to the surgery.

Results: The severity of nasal obstruction measured by visual analog scale score decreased statistically significantly in all the groups, including placebo. Radiofrequency ablation (P = .03), diode laser (P = .02), and microdebrider-assisted inferior turbinoplasty (P = .04) all decreased the symptom score of the severity of nasal obstruction statistically significantly more compared to the placebo procedure.

Conclusions: The placebo effect had a large role in the overall improvement of the severity of nasal obstruction after the inferior turbinate surgery. However, all three techniques provided a statistically significant additional reduction of the severity of nasal obstruction compared to the placebo procedure.

Level Of Evidence: 1b. Laryngoscope, 128:1997-2003, 2018.
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http://dx.doi.org/10.1002/lary.27103DOI Listing
September 2018

Eustachian Tube Dysfunction-Related Symptoms in Chronic Nasal Obstruction Caused by Inferior Turbinate Enlargement.

Ann Otol Rhinol Laryngol 2017 Dec 4;126(12):798-803. Epub 2017 Oct 4.

1 Department of Otorhinolaryngology, Tampere University Hospital, Tampere, Finland.

Objective: The aim of this study was to evaluate the relationship between chronic nasal obstruction caused by inferior turbinate enlargement and Eustachian tube dysfunction-related symptoms using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) as an assessment method.

Methods: A total of 80 adults were enrolled. Group 1 comprised consecutive patients with enlarged inferior turbinates and group 2 comprised healthy controls. The ETDQ-7 scores and tympanometry results of both groups were analyzed and compared.

Results: The median total scores of the ETDQ-7 in groups 1 and 2 were 1.9 (interquartile range, 1.4-2.8) and 1.1 (interquartile range, 1.0-1.7), respectively ( P < .001). There was no significant difference in the abnormal tympanometry results between the groups. There was no significant difference in the ETDQ-7 total score between the patients with allergic sensitization and other patients in group 1.

Conclusions: Patients with inferior turbinate enlargement have more symptoms related to Eustachian tube dysfunction than healthy controls. Most patients with Eustachian tube dysfunction had normal tympanometry and normal otoscopy, which indicates a baro-challenge-induced Eustachian tube dysfunction. Whether the patient has allergic sensitization or not does not seem to cause a difference in symptoms related to Eustachian tube dysfunction.
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http://dx.doi.org/10.1177/0003489417735538DOI Listing
December 2017

The effect of inferior turbinate surgery on ear symptoms.

Laryngoscope 2018 03 22;128(3):568-572. Epub 2017 Aug 22.

Department of Otorhinolaryngology, Tampere University Hospital, Tampere, Finland.

Objective: The aim of this placebo-controlled study was to evaluate the effect of various inferior turbinate surgery techniques on Eustachian tube dysfunction-related symptoms.

Study Design: Outcomes were evaluated using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and tympanometry results.

Methods: A total of 72 consecutively blinded and randomized adult patients with enlarged inferior turbinates due to persistent year-round rhinitis underwent either a radiofrequency ablation, diode laser, microdebrider-assisted inferior turbinoplasty, or sham surgery procedure. Assessments were conducted prior to surgery and 3 months subsequent to the surgery.

Results: In the evaluation of all patients, radiofrequency ablation, microdebrider-assisted inferior turbinoplasty, and sham surgery procedures decreased the ETDQ-7 total score significantly. In a three-way analysis of covariance, there were no significant differences in the results between sham surgery and any of the active treatment procedures. Allergic sensitization, sex, and age also had no effect on the results. There were no significant changes in the pre- and postoperative amounts of abnormal tympanometry curves or in the pre- and postoperative tympanometric peak pressure values in the actively treated patients or in the sham surgery group.

Conclusion: The improvement of Eustachian tube dysfunction-related symptoms due to surgery of the anterior half of the inferior turbinate was found to be equal to placebo. The findings of this study do not support the use of reduction of the anterior half of the inferior turbinate as a sole procedure intended to treat the ear symptoms assessed by the ETDQ-7 questionnaire.

Level Of Evidence: 1b. Laryngoscope, 128:568-572, 2018.
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http://dx.doi.org/10.1002/lary.26823DOI Listing
March 2018

Balloon Eustachian tuboplasty under local anesthesia: Is it feasible?

Laryngoscope 2017 May 3;127(5):1021-1025. Epub 2017 Feb 3.

Department of Otorhinolaryngology-Head and Neck Surgery, Head and Neck Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objective: To study whether balloon Eustachian tuboplasty (BET) is a feasible and safe procedure under local anesthesia.

Study Design: Prospective multicenter case-control study.

Methods: Patients undergoing either BET (n = 13) or endoscopic sinus surgery (ESS) (n = 12) under local anesthesia, with the possibility of sedation and analgesia, were monitored during the procedure and recovery period for possible adverse effects. After the procedure, the patients responded to a questionnaire assessing their experience.

Results: No adverse effects were detected in the BET group. Patients in the BET group reported similar Visual Analog Scale scores for pain during the operation as the ESS group (5.0 ± 0.7 vs. 3.2 ± 0.7, mean ± standard error of the mean). However, patients in the BET group experienced more discomfort (4.2 ± 0.6 vs. 2.5 ± 0.3, respectively, P = 0.049). Seventy-seven and 92% of the patients in the BET and ESS groups, respectively, considered the anesthesia and pain relief to be sufficient. Patients from both the BET and ESS groups were almost devoid of pain 1 to 2 hours postoperatively (0.8 ± 0.2 and 1.4 ± 0.3, respectively). In total, 12 of 13 patients in the BET group, and all 12 patients in the ESS group, would choose local anesthesia with sedation and analgesia if they needed to undergo the same procedure again.

Conclusion: BET is a safe and feasible procedure under monitored anesthesia care, including local anesthesia along with sedation and analgesia. There is need for further methodological improvement to reduce pain and discomfort during the operation.

Level Of Evidence: 4. Laryngoscope, 127:1021-1025, 2017.
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http://dx.doi.org/10.1002/lary.26488DOI Listing
May 2017

Next-Generation Sequencing Combined with Specific PCR Assays To Determine the Bacterial 16S rRNA Gene Profiles of Middle Ear Fluid Collected from Children with Acute Otitis Media.

mSphere 2017 Mar-Apr;2(2). Epub 2017 Mar 22.

Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.

The aim of the study was to analyze the bacteriome of acute otitis media with a novel modification of next-generation sequencing techniques. Outpatient children with acute otitis media were enrolled in the study, and middle ear fluids were collected during 90 episodes from 79 subjects aged 5 to 42 months (median age, 19 months). The bacteriome profiles of middle ear fluid samples were determined by a nested-PCR amplification of the 16S rRNA gene (V4 region), followed by mass sequencing. The profiling results were compared to the results of specific PCR assays targeting selected prevalent pathogens. Bacteriome profiling using nested amplification of low-volume samples was aided by a bioinformatic subtraction of signal contaminants from the recombinant polymerase, achieving a sensitivity slightly lower than that of specific PCR detection. was detected in 28 (31%) samples, in 24 (27%), in 18 (20%), spp. in 21 (23%), in 5 (5.6%), in 3 (3.3%), and other bacteria in 14 (16%) using bacteriome profiling. was the dominant pathogen in 14 (16%) samples, in 15 (17%), in 5 (5.6%), in 2, and in 2. Weaker signals of , , and were noted in several samples. Fourteen samples (16%) were not explainable by bacterial pathogens; novel causative agents were not detected. In conclusion, unbiased bacteriome profiling helped in depicting the true mutual quantitative ratios of ear bacteria, but at present, its complicated protocol impedes its routine clinical use. Although , , and have been long established as the most important pathogens in acute otitis media using culture and specific PCR assays, the knowledge of their mutual quantitative relations and possible roles of other bacteria is incomplete. The advent of unbiased bacteriome 16S rRNA gene profiling has allowed the detection of nearly all bacteria present in the sample, and it helps in depicting their mutual quantitative ratios. Due to the difficulties in performing mass sequencing in low-volume samples, only a few bacteriome-profiling studies of otitis media have been published, all limited to cases of chronic otitis media. Here, we present a study on samples obtained from young children with acute otitis media, successfully using a strategy of nested PCR coupled with mass sequencing, and demonstrate that the method can confer quantitative information hardly obtainable by other methods.
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http://dx.doi.org/10.1128/mSphere.00006-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362748PMC
March 2017

A survey on the feasibility of surface EMG in facial pacing.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:1688-1691

A survey on the feasibility of surface electromyography (EMG) measurements in facial pacing is presented. Pacing for unilateral facial paralysis consists of the measurement of activity from the healthy side of the face and functional electrical stimulation to reanimate the paralyzed one. The goal of this study is to evaluate the feasibility of surface EMG as a measurement method to detect muscle activations and to determine their intensities. Prior work is discussed, and results from experiments where 12 participants carried out a set of facial movements are presented. EMG was registered from zygomaticus major (smile), orbicularis oris (lip pucker), orbicularis oculi (eye blink), corrugator supercilii (frown), and masseter (chew). Most important facial functions that are limited due to the paralysis are blinking, smiling, and puckering. With majority of the participants, crosstalk between the measured EMG channels was found to be acceptably small to be able to pace smiling and puckering based on detecting their contraction intensities from the healthy side. However, pacing blinking based on orbicularis oculi EMG measurement does not seem possible due to crosstalk from other muscles, but the electro-oculographic (EOG) signals that couple to the same measurement channel could help to detect eye blinks and trigger stimuli. Futhermore, masseter greatly disturbs EMG measurement of most facial muscles, which needs to be addressed in the pacing system to avoid falsely interpreting its activity as the activity of another muscle.
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http://dx.doi.org/10.1109/EMBC.2016.7591040DOI Listing
August 2016

Significance of imaging in the diagnosis of olfactory disorder.

Ear Nose Throat J 2017 Feb;96(2):E13-E17

Department of Otorhinolaryngology, Tampere University Hospital, Teiskontie 35, 33521 Tampere, Finland.

The aim of this retrospective analysis was to examine olfactory disorders among the patients in the Ear, Nose, and Throat Clinic of Tampere University Hospital, Finland, from 2001 to 2011, and to evaluate the necessity of imaging in the examination of patients with olfactory disorders. Charts of 143 consecutive patients with a primary olfactory disorder were examined, and 69 patients who had undergone the necessary testing were included in the study. The most common causes of olfactory disorder were upper respiratory infection (23%), chronic rhinosinusitis (19%), head trauma (17%), and allergic or nonallergic rhinitis (6%). In 25% of the patients, no obvious cause for the symptoms was found. Computed tomography (CT) scans were normal in 37 of 52 (71%) patients and magnetic resonance imaging was normal in 21 of 25 (84%) patients. No intracranial or intranasal tumors were found in the overall cohort. Of the patients with additional symptoms (facial pain, headache, nasal discharge, or stuffiness), 58% had chronic rhinosinusitis. Of the patients with no additional symptoms or signs associated with chronic rhinosinusitis on clinical evaluation, only 2% had chronic rhinosinusitis on imaging. Only the detection of chronic rhinosinusitis and head trauma had clinical value in the determination of the etiology. A sinonasal CT scan should be considered in patients who have at least one symptom associated with sinusitis in addition to an olfactory disorder to confirm the etiology and to find those patients who may benefit from medical therapy or surgical treatment.
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http://dx.doi.org/10.1177/014556131709600213DOI Listing
February 2017

Inter-observer agreement of paranasal sinus computed tomography scans.

Acta Otolaryngol 2017 Jun 16;137(6):611-617. Epub 2016 Dec 16.

a Transplantation Laboratory , Haartman Institute, University of Helsinki , Helsinki , Finland.

Conclusion: The study demonstrated considerable inter-observer variation in certain surgically important structures. This would indicate the significance for consultation when evaluating sinus CT scans of CRS patients for planned advanced sinus surgery.

Objectives: After the failure of medical treatment of chronic rhinosinusitis (CRS), the need for surgery and the pre-operative planning of safe surgery is based on computed tomography (CT) findings. The aim of this prospective study was to compare inter-observer agreement of anatomical and surgical structures of sinus CT scans. The hypothesis was that the agreement between observers is good.

Methods: Of these 57 CRS patients, Lund-Mackay (LM) scores and 43 other structural parameters were analyzed blinded. The reproducibility of the findings between three observers, a radiologist, an Ear, nose and throat (ENT) surgeon, and an ENT resident, were compared.

Results: In general, there was moderate inter-observer agreement of the structures by Cohen's kappa coefficient. Poor reproducibility was observed in the following structures: optic nerve, insertion of the uncinated process, anterior ethmoidal artery, and Keros class.
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http://dx.doi.org/10.1080/00016489.2016.1262552DOI Listing
June 2017

Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children.

J Clin Microbiol 2016 09 13;54(9):2373-9. Epub 2016 Jul 13.

Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague, and University Hospital Motol, Prague, Czech Republic.

According to studies based on bacterial cultures of middle ear fluids, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis have been the most common pathogens in acute otitis media. However, bacterial culture can be affected by reduced viability or suboptimal growth of bacteria. PCR detects bacterial DNA from samples with greater sensitivity than culture. In the present study, we analyzed the middle ear pathogens with both conventional culture and semiquantitative real-time PCR in 90 middle ear fluid samples obtained from children aged 5 to 42 months during acute otitis media episodes. Samples were tested for the presence of S. pneumoniae, H. influenzae, M. catarrhalis, Alloiococcus otitidis, Staphylococcus aureus, and Pseudomonas aeruginosa One or more bacterial pathogens were detected in 42 (47%) samples with culture and in 69 (77%) samples with PCR. According to PCR analysis, M. catarrhalis results were positive in 42 (47%) samples, H. influenzae in 30 (33%), S. pneumoniae in 27 (30%), A. otitidis in 6 (6.7%), S. aureus in 5 (5.6%), and P. aeruginosa in 1 (1.1%). Multibacterial etiology was seen in 34 (38%) samples, and M. catarrhalis was detected in most (85%) of those cases. Fifteen signals for M. catarrhalis were strong, suggesting a highly probable etiological role of the pathogen. In conclusion, even though M. catarrhalis is often a part of mixed flora in acute otitis media, a considerable proportion of cases may be primarily attributable to this pathogen.
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http://dx.doi.org/10.1128/JCM.01146-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005485PMC
September 2016

Factors affecting revision rate of chronic rhinosinusitis.

Laryngoscope Investig Otolaryngol 2016 08 5;1(4):96-105. Epub 2016 Jul 5.

Haartman Institute, University of Helsinki (a.k., r.s., r.r., s.t-s.).

Objective: Chronic rhinosinusitis (CRS) is a variable multifactorial disease. It can be divided into forms with nasal polyps (CRSwNP) and without (CRSsNP). Sinus and/or nasal polypectomy surgery are considered if maximal conservative treatment is insufficient. The predictive factors of the need of revision surgery comprise mostly the CRSwNP phenotype and are not fully understood.

Study Design: The aim of this follow-up study was to evaluate the factors associated with the revision surgery rate in CRS patients with variable extent of disease.

Methods: Data of CRS patients (N = 178) undergoing sinus surgery and/or nasal polypectomy in 2001 to 2010 were used. Patient characteristics and follow-up data were collected from patient records and questionnaires. Associations were analyzed by Fisher's exact, Mann Whitney U, and the Kaplan-Meier method with log-rank test. Unadjusted Cox's proportional hazard models were used for 12 variables and were fitted for the need for revision sinus surgery and/or nasal polypectomy during follow-up of in average 9 years.

Results: The proportion of CRS patients who had undergone revision in 5 years was 9.6%. After adjustment, the following factors associated significantly with the need for recurrent CRS surgery: allergic rhinitis, corticosteroid treatment, previous surgery of CRS, and recurrent NP.

Conclusion: Increased risk of progressive CRS phenotypes with the need for revision surgery would putatively be recognized by relatively simple clinical questions. Further studies with increased sample size are needed to evaluate whether these predictive factors would be relevant for developing better detection and management of progressive CRS.

Level Of Evidence: 2b.
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http://dx.doi.org/10.1002/lio2.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510254PMC
August 2016

High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2016 Dec 21;273(12):4515-4524. Epub 2016 Jun 21.

Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Helsinki, Finland.

Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.
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http://dx.doi.org/10.1007/s00405-016-4150-yDOI Listing
December 2016

Quality of Life and Hearing Eight Years After Sudden Sensorineural Hearing Loss.

Laryngoscope 2017 04 21;127(4):927-931. Epub 2016 Jun 21.

Department of Ear and Oral Diseases, Tampere University Hospital, Tampere, Finland.

Objectives/hypothesis: To explore long-term hearing results, quality of life (QoL), quality of hearing (QoH), work-related stress, tinnitus, and balance problems after idiopathic sudden sensorineural hearing loss (ISSNHL).

Study Design: Cross-sectional study.

Methods: We reviewed the audiograms of 680 patients with unilateral ISSNHL on average 8 years after the hearing impairment, and then divided the patients into two study groups based on whether their ISSNHL had recovered to normal (pure tone average [PTA] ≤ 30 dB) or not (PTA > 30 dB). The inclusion criteria were a hearing threshold decrease of 30 dB or more in at least three contiguous frequencies occurring within 72 hours in the affected ear and normal hearing in the contralateral ear. Audiograms of 217 patients fulfilled the criteria. We reviewed their medical records; measured present QoL, QoH, and work-related stress with specific questionnaires; and updated the hearing status.

Results: Poor hearing outcome after ISSNHL was correlated with age, severity of hearing loss, and vertigo together with ISSNHL. Quality of life and QoH were statistically significantly better in patients with recovered hearing, and the patients had statistically significantly less tinnitus and balance problems. During the 8-year follow-up, the PTA of the affected ear deteriorated on average 7 dB, and healthy ear deteriorated 6 dB.

Conclusion: Idiopathic sudden sensorineural hearing loss that failed to recover had a negative impact on long-term QoL and QoH. The hearing deteriorated as a function of age similarly both in the affected and the healthy ear, and there were no differences between the groups. The cumulative recurrence rate for ISSNHL was 3.5%.

Level Of Evidence: 4 Laryngoscope, 127:927-931, 2017.
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http://dx.doi.org/10.1002/lary.26133DOI Listing
April 2017

Treatment of rhinosinusitis and histopathology of nasal mucosa: A controlled, randomized, clinical study.

Laryngoscope 2016 12 3;126(12):2652-2658. Epub 2016 Jun 3.

Department of Otorhinolaryngology and Oral Diseases, Tampere University and University Hospital of Tampere, Tampere, Finland.

Objectives/hypothesis: To study the pathology of upper airway mucosa, as well as valuate and compare changes in pathology after the treatment of chronic rhinosinusitis (CRS) patients with balloon sinuplasty versus uncinectomy.

Methods: A prospective randomized controlled trial in patients with CRS of the maxillary sinuses without severe pathology of other sinuses. Patients were randomized into two groups: uncinectomy and balloon sinuplasty. The main variables in our study are histopathology of nasal mucosa and expression of metalloproteinase-9 protein. These parameters were analyzed preoperatively and at 3 months, 6 months, and 12 months postoperatively.

Results: Thickened epithelium, absence of cilia, metaplasia of epithelium, hyperplasia of mucosal glands, angiogenesis, and increased inflammatory cells were observed in the majority of preoperative samples. History of allergy was associated with a higher number of goblet cells, and shedding of epithelium was associated with worse quality of life. A higher number of inflammatory cells were associated with an increased number of goblet cells preoperatively, as well as after treatment. Both treatments resulted in a decrease of inflammation in the mucosa and epithelium. Hypertrophy of the mucosal glands, hyperplasia of blood vessels, and mucosal edema decreased after treatment. These changes were more noticeable in uncinectomy group. Balloon sinuplasty was associated with a higher number of inflammatory cells at 6 months after treatment (P = 0.05).

Level Of Evidence: 1b. Laryngoscope, 126:2652-2658, 2016.
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http://dx.doi.org/10.1002/lary.26072DOI Listing
December 2016

Antibiotic resistance in pathogens causing acute otitis media in Finnish children.

Int J Pediatr Otorhinolaryngol 2016 Jun 11;85:91-4. Epub 2016 Apr 11.

Department of Otorhinolaryngology and Head and Neck Surgery, Tampere University Hospital and School of Medicine, University of Tampere, 33520 Tampere, Finland.

Introduction: Microbiology and susceptibility of middle ear pathogens in children change over time and antibiotic resistance is increasing globally. For the clinicians it is important to be up to date about the resistance situation when considering antibiotic treatment in acute otitis media (AOM). In this study we analysed the resistance profile of AOM pathogens in out-patient children in Finland.

Methods And Materials: A total of 41 culture positive middle ear fluid (MEF) samples were analysed for bacteria and the presence of antibiotic resistant strains. The samples were obtained from children aged six - 39 months who participated in the otitis media trial during one year period.

Results: The most common pathogen was Haemophilus influenzae 17 (40%), followed by Streptococcus pneumoniae in 15 (35%) and Moraxella catarrhalis in 8 (19%). Other pathogens were detected in 3 (7%) of cases. Antibiotic resistance or diminished sensitivity was seen in 63% of the detected bacteria and 28% of pathogens produced beta-lactamase.

Conclusions: Antibiotic resistant bacterial strains causing AOM have increased in Finland. Nevertheless, most of the pathogens (72%) were sensitive to amoxicillin, which is still recommended as the first line antibiotic in the treatment of AOM.
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http://dx.doi.org/10.1016/j.ijporl.2016.03.037DOI Listing
June 2016

Myxoinflammatory fibroblastic sarcoma of the nose: First reported case at an unusual location (nasal dorsum), with a review of the literature.

Ear Nose Throat J 2016 Mar;95(3):E32-5

Department of Ear and Oral Diseases, Tampere University Hospital, PO Box 2000, 33 521 Tampere, Finland.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade, malignant, soft-tissue tumor that typically affects the distal extremities of middle-aged patients. In most cases, it presents as a painless, slowly growing mass within the subcutaneous tissue. It is associated with a low rate of metastasis but a high rate of local recurrence. In addition to the distal extremities, MIFS has been reported in the thigh, arm, forearm, groin, upper back, neck, and temporal area. As far as we know, no case has been previously reported in the nasal area. We report for the first time a case of MIFS presenting on the dorsum of the nose. The painless, 3.0-cm tumor was initially mistaken for reticular erythematous mucinosis, a benign skin condition that occurs when fibroblasts produce abnormally large amounts of mucopolysaccharides. The tumor was surgically removed in its entirety with surgical margins of 3 to 5 mm. During 4 years of follow-up, no clinical or radiologic evidence of a recurrence or metastasis was seen. We discuss the imaging and histologic features of MIFS, as well as its clinical management and follow-up, and we review related reports in the literature.
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http://dx.doi.org/10.1177/014556131609500304DOI Listing
March 2016

The expression and prognostic relevance of indoleamine 2,3-dioxygenase in tongue squamous cell carcinoma.

Acta Otolaryngol 2016 Jul 16;136(7):729-35. Epub 2016 Mar 16.

a Haartman Institute, University of Helsinki , Helsinki , Finland ;

Conclusion IDO might be useful for predicting progression of primary tumor stage T2 and T3 in tongue squamous cell carcinoma (TSCC), but does not seem like a specific biomarker for diagnosing TSCC and predicting patient survival. Objectives Indoleamine 2,3-dioxygenase (IDO) is expressed in many cells and it catabolises the essential amino acid tryptophan to kynurenine. IDO acts as an immune modulator through suppression of T-cell immunity and other pathways. In cancer cells, IDO has been proposed to promote tumor progression by enabling malignant cells to escape from the immune system. The aim of this study was to evaluate the association and prognostic relevance of IDO expression in TSCC. Method One hundred and eight retrospective tongue and lymph node specimens were stained immunohistochemically with monoclonal antibody anti-indoleamine 2,3-dioxygenase. The relative abundance of IDO positive epithelial cells, IDO staining intensity, and inflammation were assessed semi-quantitatively with light microscopy. Results IDO was expressed stronger in tongue hyperplasia than in TSCC. However, IDO expression associated with poor survival in the sub-groups with primary tumor stage T2-T4 and in the sub-group with strong inflammation in tumors' invasive front.
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http://dx.doi.org/10.3109/00016489.2016.1152631DOI Listing
July 2016