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  • 1.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA..
    Kamel, Wael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, e0177275Article in journal (Refereed)
    Abstract [en]

    We have used high-throughput small RNA sequencing to characterize viral small RNA expression in purified tonsillar B and T lymphocytes isolated from patients tested positive for Epstein-Barr virus (EBV) or human adenovirus (HAdV) infections, respectively. In the small set of patients analyzed, the expression profile of EBV and HAdV miRNAs could not distinguish between patients diagnosed with tonsillar hypertrophy or chronic/recurrent tonsillitis. The EBV miR-BART expression profile among the patients diagnosed with tonsillar diseases resembles most closely the pattern seen in EBV+ tumors (Latency II/I). The miRBARTs that appear to be absent in normal EBV infected cells are essentially all detectable in the diseased tonsillar B lymphocytes. In the EBV+ B cells we detected 44 EBV miRBARTs derived from the proposed BART precursor hairpins whereof five are not annotated in miRBase v21. One previously undetected miRNA, BART16b-5p, originates from the miR-BART16 precursor hairpin as an alternative 5 A miR-BART16 located precisely upstream of the annotated miR-BART16-5p. Further, our analysis revealed an extensive sequence variation among the EBV miRNAs with isomiRs having a constant 5 A end but alternative 3 A ends. A range of small RNAs was also detected from the terminal stem of the EBER RNAs and the 3 A part of v-snoRNA1. During a lytic HAdV infection in established cell lines the terminal stem of the viral non-coding VA RNAs are processed to highly abundant viral miRNAs (mivaRNAs). In contrast, mivaRNA expression in HAdV positive tonsillar T lymphocytes was very low. The small RNA profile further showed that the 5 A mivaRNA from VA RNAI and the 3 A mivaRNA from VA RNAII were as predicted, whereas the 3 A mivaRNA from VA RNAI showed an aberrant processing upstream of the expected Dicer cleavage site.

  • 2.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandström, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lidian, Adnan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, e0154814Article in journal (Refereed)
    Abstract [en]

    Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.

  • 3.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandström, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Efficient Isolation Protocol for B and T Lymphocytes from Human Palatine Tonsils2015In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, Vol. 105, e53374Article in journal (Refereed)
    Abstract [en]

    Palatine tonsils are a rich source of B and T lymphocytes. Here we provide an easy, efficient and rapid protocol to isolate B and T lymphocytes from human palatine tonsils. The method described has been specifically adapted for studies of the viral etiology of tonsil inflammation known as tonsillitis.

  • 4.
    Berglin, Cecilia Engmer
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Pierre, Pernilla Videhult
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ekborn, Andreas
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hultcrantz, Malou
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration2015In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 10, 985-994 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.

  • 5. Berglin, Cecilia Engmér
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Counter, S Allen
    Klason, Tomas
    Ekborn, Andreas
    Magnetic Resonance Imaging of the Middle and Inner Ear After Intratympanic Injection of a Gadolinium-Containing Gel2014In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 35, no 3, 526-532 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the distribution and elimination of a gadolinium containing high viscosity formulation of sodium hyaluronan (HYA gel) after injection to the middle ear.

    MATERIALS AND METHODS:

    The T1 contrast agent gadolinium-diethylenetriamine pentaacetic acid-bis methylamine (Gd-DTPA-BMA) was added to HYA gel and delivered to the middle ear of 13 albino guinea pigs by 3 different ways of injection. Magnetic resonance imaging was performed with a 4.7 T MRI system using a T1-weighted 3-dimentional rapid acquisition with relaxation enhancement sequence.

    RESULTS:

    An injection technique where the Gd-DTPA-BMA-containing HYA gel was delivered to the middle ear through a percutaneous injection through the auditory bulla after a small incision had been made in the tympanic membrane gave the best filling of the middle ear, covering the cochlea and the region of the round window niche for 24 hours in a majority of the ears studied. Ears injected without an incision in the tympanic membrane showed an immediate uptake of Gd-DTPA-BMA in the inner ear as a sign of rupture of the round window membrane.

    CONCLUSION:

    A percutaneous injection of a HYA gel into the tympanic bulla is distributed in a predictable way and gives a good filling of the middle ear cavity. The HYA gel remains in close vicinity to the RWM for more than 24 hours. Injection should be performed after an incision of the tympanic membrane has been made to prevent rupture of the round window membrane.

  • 6. Boldrup, L.
    et al.
    Coates, P. J.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wilms, T.
    Fahraeus, R.
    Nylander, K.
    Downregulation of miRNA-424: a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma2015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 11, 1760-1765 p.Article in journal (Refereed)
    Abstract [en]

    Background: The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. Methods: On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. Results: Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. Conclusions: Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.

  • 7.
    Boldrup, Linda
    et al.
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Gu, Xiaolian
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Coates, Philip J.
    Masaryk Mem Canc Inst, RECAMO, Brno 65653, Czech Republic..
    Norberg-Spaak, Lena
    Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden..
    Fahraeus, Robin
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden.;Masaryk Mem Canc Inst, RECAMO, Brno 65653, Czech Republic.;Univ Paris 07, Hop St Louis, Inst Genet Mol, F-75010 Paris, France..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden.
    Wilms, Torben
    Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden..
    Nylander, Karin
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 12, 19389-19402 p.Article in journal (Refereed)
    Abstract [en]

    Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.

  • 8.
    Counter, S. Allen
    et al.
    Harvard Med Sch, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA.;Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA..
    Buchanan, Leo H.
    Harvard Univ Hlth Serv, Audiol Clin, Dept Otolaryngol, Cambridge, MA USA..
    Ortega, Fernando
    Univ San Francisco Quito, Galapagos Inst Arts & Sci GAIAS, Colegio Ciencias Salud, Escuela Salud Publ, Quito, Ecuador..
    Jacobs, Anthony B.
    Harvard Biol Labs, Cambridge, MA USA..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Assessment of the Brainstem- Mediated Stapedius Muscle Reflex in Andean Children Living at High Altitudes2017In: High Altitude Medicine & Biology, ISSN 1527-0297, E-ISSN 1557-8682, Vol. 18, no 1, 37-45 p.Article in journal (Refereed)
    Abstract [en]

    This study examined the physiological thresholds, amplitude growth, and contraction duration of the acoustic stapedius reflex (ASR) in Andean children aged 2-17 years living at altitudes of 2850m (Altitude I Group) and 3973m (Altitude II Group) as part of a general medical assessment of the health status of the children. The brainstem-mediated ASR reveals the integrity of the neuronal components of the auditory reflex arc, including the cochlea receptors, eight cranial nerves, and brainstem neural projections to the cochlear nuclei, bilateral superior olivary nuclei, facial nerve nuclei, and facial nerve and its stapedius branch. Uncrossed (ipsilateral) and crossed (contralateral) ASR thresholds (ASRT), ASR amplitude growth (ASRG) function, and ASR muscle contraction duration (decay/ fatigue) (ASRD) were measured noninvasively with 500, 1000 Hz and broadband (bandwidth = 125-4000 Hz) noise stimulus activators using a middle ear immittance system. Oxygen saturation (SaO(2)) level and heart rate were measured in a subsample of the study group. Statistical analyses revealed that the Altitude I and Altitude II groups had ASRT, ASRG function, and ASRD rates comparable to children at sea level and that the two groups were not significantly different for any of the ASR measures. No significant association was found between SaO(2) or heart rate and ASRT, growth, and muscle fatigue rate. In conclusion, the assessment of the ASR in children in the high-altitude groups revealed normal function. Furthermore, the results indicate no adverse oto-physiological effects of altitude on the brainstem-mediated ASR at elevations between 2850 and 4000m and suggest normal middle ear and auditory brainstem function.

  • 9.
    Counter, S. Allen
    et al.
    Harvard Univ, Harvard Med Sch, Dept Neurol, Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA.;Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA..
    Buchanan, Leo H.
    Harvard Univ, Dept Otolaryngol, Audiol Clin, Hlth Serv, 16 Divin Ave, Cambridge, MA 02138 USA..
    Ortega, Fernando
    Univ San Francisco Quito, Escuela Salud Publ, Colegio Ciencias Salud, Quito, Ecuador.;Univ San Francisco Quito, Galapagos Inst Arts & Sci GAIAS, Quito, Ecuador..
    Jacobs, Anthony B.
    Harvard Univ, Harvard Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Middle Ear Function and Pathophysiology in Andean Children Living at High Altitudes2017In: High Altitude Medicine & Biology, ISSN 1527-0297, E-ISSN 1557-8682, Vol. 18, no 2, 163-170 p.Article in journal (Refereed)
    Abstract [en]

    The extent of altitude-related middle ear disorders in children native to high altitudes is unclear. This study examined middle ear pathophysiology in two groups of children living in high-altitude Ecuadorian Andean communities by investigating middle ear pressure (MEP), tympanic membrane compliance (TMC), and ear canal volume (ECV) using tympanometry, and by otological examination. Altitude I Group lived at 2850m, and Altitude II Group resided at around 4000m. The two high-altitude groups were compared with a reference group of children residing at sea level. Mean MEP was -3.6daPa (SD: 39.2), 3.5daPa (SD: 28.7), and 1.3daPa (SD: 13.6) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The MEP was not significantly different among the three groups. Mean TMC was 0.63cm3 (SD: 0.51), 0.60cm3 (SD: 0.43), and 0.60cm3 (SD: 0.24) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The TMC was not significantly different among the three groups. Mean ECV was 1.1 (SD: 0.26), 1.2 (SD: 0.26), and 1.0 (SD: 0.23) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The difference in ECV between Altitude I Group and Altitude II Group was significant (p=0.043), as was the difference between Altitude II Group and the Sea Level Group (p=0.001). ECV did not differ significantly between Altitude I Group and the Sea Level Group. Otological examination revealed a low incidence of ear canal and middle ear pathology. In conclusion, tympanometric and otological findings did not reveal a high incidence of middle ear pathophysiology in children living at altitudes as high as around 4000m.

  • 10. Counter, S Allen
    et al.
    Damberg, Peter
    Aski, Sahar Nikkhou
    Nagy, Kálmán
    Berglin, Cecilia Engmér
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Experimental Fusion of Contrast Enhanced High-Field Magnetic Resonance Imaging and High-Resolution Micro-Computed Tomography in Imaging the Mouse Inner Ear2015In: The Open Neuroimaging Journal, ISSN 1874-4400, E-ISSN 1874-4400, Vol. 9, 7-12 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Imaging cochlear, vestibular, and 8th cranial nerve abnormalities remains a challenge. In this study, the membranous and osseous labyrinths of the wild type mouse inner ear were examined using volumetric data from ultra high-field magnetic resonance imaging (MRI) with gadolinium contrast at 9.4 Tesla and high-resolution micro-computed tomography (µCT) to visualize the scalae and vestibular apparatus, and to establish imaging protocols and parameters for comparative analysis of the normal and mutant mouse inner ear.

    METHODS: For in vivo MRI acquisition, animals were placed in a Milleped coil situated in the isocenter of a horizontal 9.4 T Varian magnet. For µCT examination, cone beam scans were performed ex vivo following MRI using the µCT component of a nanoScan PET/CT in vivo scanner.

    RESULTS: The fusion of Gd enhanced high field MRI and high-resolution µCT scans revealed the dynamic membranous labyrinth of the perilymphatic fluid filled scala tympani and scala vestibule of the cochlea, and semicircular canals of the vestibular apparatus, within the µCT visualized contours of the contiguous osseous labyrinth. The ex vivo µCT segmentation revealed the surface contours and structural morphology of each cochlea turn and the semicircular canals in 3 planes.

    CONCLUSIONS: The fusion of ultra high-field MRI and high-resolution µCT imaging techniques were complementary, and provided high-resolution dynamic and static visualization of the complex morphological features of the normal mouse inner ear structures, which may offer a valuable approach for the investigation of cochlear and vestibular abnormalities that are associated with birth defects related to genetic inner ear disorders in humans.

  • 11. Counter, S Allen
    et al.
    Nikkhou, Sahar
    Brené, Stefan
    Damberg, Peter
    Sierakowiak, Adam
    Klason, Tomas
    Berglin, Cecilia Engmér
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    MRI evidence of endolymphatic impermeability to the gadolinium molecule in the in vivo mouse inner ear at 9.4 tesla2013In: The Open Neuroimaging Journal, ISSN 1874-4400, E-ISSN 1874-4400, Vol. 7, 27-31 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Previous in vivo experimental magnetic resonance imaging (MRI) investigations of the mammalian inner ear at 4.7 Tesla have indicated that intravenously injected gadolinium (Gd) penetrates the perilymphatic labyrinth, but not the endolymphatic membranous labyrinth. In the present study, high field MRI at 9.4T was used to visualize the in vivo mouse vestibulo-cochlea system, and to determine whether the endolymphatic system is permeable to a Gd complex.

    METHODS:

    A 9.4 T Varian magnet equipped with a 12 cm inner diameter gradient system with maximum gradient strength of 600 mT/m, a millipede coil (Varian design) and a Gd contrast agent were used for image acquisition in the normal C57 BL-6 mouse.

    RESULTS:

    High-resolution 2D and 3D images of the mouse cochlea were acquired within 80 minutes following intravenous injection of Gd. Gd initially permeated the perilymphatic scala tympani and scala vestibuli, and permitted visualization of both cochlear turns from base to apex. The superior, inferior and lateral semicircular canals were subsequently visualized in 3 planes. The membranous endolymphatic labyrinth was impermeable to intravenously injected Gd, and thus showed no apparent uptake of Gd at 9.4T.

    CONCLUSION:

    The 9.4T field strength MRI permitted acquisition of high resolution images of anatomical and physiological features of the normal, wild type mouse perilymphatic inner ear in vivo, and provided further evidence that the endolymphatic system is impermeable to intravenously injected Gd.

  • 12.
    Counter, S. Allen
    et al.
    Harvard Univ, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA..
    Nikkhou-Aski, Sahar
    Karolinska Univ Sjukhuset Solna, Karolinska Expt Res & Imaging Ctr, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Damberg, Peter
    Karolinska Univ Sjukhuset Solna, Karolinska Expt Res & Imaging Ctr, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Berglin, Cecilia Engmer
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ultra-high-field (9.4 T) MRI Analysis of Contrast Agent Transport Across the Blood-Perilymph Barrier and Intrastrial Fluid-Blood Barrier in the Mouse Inner Ear2017In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 38, no 7, 1052-1059 p.Article in journal (Refereed)
    Abstract [en]

    Hypothesis: Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla.

    Background: A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI.

    Methods: Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces.

    Results: ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear.

    Conclusion: Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.

  • 13. Dammeyer, Pascal
    et al.
    Hellberg, Victoria
    Wallin, Inger
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Shoshan, Maria
    Ehrsson, Hans
    Arner, Elias S. J.
    Kirkegaard, Mette
    Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures2014In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 5, 448-454 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion: Inhibition of thioredoxin reductase (TrxR) may be a contributing factor in cisplatin- induced ototoxicity. Direct exposure of organ of Corti to cisplatin and oxaliplatin gives equal loss of hair cells. Objectives: Platinum- containing drugs are known to target the anti- oxidant selenoprotein TrxR in cancer cells. Two such anti- cancer, platinum- containing drugs, cisplatin and oxaliplatin, have different side effects. Only cisplatin induces hearing loss, i.e. has an ototoxic side effect that is not seen after treatment with oxaliplatin. The objective of this study was to evaluate if TrxR is a target in the cochlea. Loss of outer hair cells was also compared when cisplatin and oxaliplatin were administered directly to the organ of Corti. Methods: Organ of Corti cell culture was used for direct exposure to cisplatin and oxaliplatin. Hair cells were evaluated and the level of TrxR was assessed. Immunohistochemical staining for TrxR was performed. An animal model was used to evaluate the effect on TrxR after treatment with cisplatin and oxaliplatin in vivo. Results: Direct exposure of cochlear organotypic cultures to either cisplatin or oxaliplatin induced comparable levels of outer hair cell loss and inhibition of TrxR, demonstrating that both drugs are similarly ototoxic provided that the cochlea becomes directly exposed.

  • 14.
    Ehrsson, Ylva Tiblom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Sundberg, Kay
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Langius-Eklöf, Ann
    Head and neck cancer patients' perceptions of quality of life and how it is affected by the disease and enteral tube feeding during treatment2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, 280-289 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To explore individual quality of life in patients with head and neck cancer from diagnosis up to 3 months after termination of radiotherapy.

    RESEARCH QUESTIONS: 1) Which areas in life are important to quality of life, and which are influenced by the disease and by having oral or enteral nutrition; and 2) Which areas in life are influenced by having a nasogastric feeding tube (NGT) or a percutaneous endoscopic gastrostomy (PEG) tube?

    MATERIAL AND METHODS: Data were collected in 36 patients. Semi-structured interviews were conducted using an extended version of the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) and analysed with content analysis.

    RESULTS: Negative and positive experiences of quality of life in general were about relation to family, own health, and leisure activities. Negative impacts on physical, psychological, existential and social problems, but also positive experiences are described by the patients related to the disease. More than half expressed eating-related problems. Enteral nutrition entailed negative and positive experiences, and no greater variations were described by the patients with NGT or PEG tube. Overall, there were interindividual variations.

    CONCLUSIONS: The patients' perception of general or disease-related quality of life was not affected by whether they had enteral nutrition or not. From the patients' perspective neither of the two feeding tubes (NGT or PEG) was clearly in favour. We suggest that more studies are needed on how the choice of enteral feeding tube can be evidence-based, and incorporating the patients' perspective.

  • 15. Engmér, Cecilia
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bagger-Sjöbäck, Dan
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Immunodefense of the round window2008In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 118, no 6, 1057-62 p.Article in journal (Refereed)
    Abstract [en]

    A systematic analysis using serial sectioning of the round window membrane (RWM) in the cynomolgus monkey was performed. Light and transmission electron microscopy (LM and TEM) revealed that the RWM rim may be endowed with gland-like structures with glyco-protein material secernated into the window niche. This was detected in one third of the specimens. The secreted material displayed waste material and scavenger cells. There was also a rich network of capillaries, lymph channels, and sinusoidal veins containing leukocytes. Their abluminal surfaces displayed mature plasma cells and monocytes. These findings suggest that in certain primates the middle ear may have developed specific immunoprotective means for disposal of foreign and noxious substances before they reach the inner ear.

  • 16.
    Farnebo, Lovisa
    et al.
    Linkoping Univ, Dept Otorhinolaryngol, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Makitie, Antti
    Univ Helsinki, Dept Otorhinolaryngol, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Karolinska Inst, Div Ear Nose & Throat Dis, Dept Clin Sci Intervent & Technol, Karolinska Univ Hosp, Stockholm, Sweden..
    A Nordic survey on the management of head and neck CUP2016In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, no 11, 1159-1163 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion: The management of Head and Neck Cancer of Unknown Primary (HNCUP) patients varies both between centres within and also between the Nordic countries. This study contributes to a continuing discussion of how to improve the accuracy of diagnosis and quality of treatment of HNCUP patients.Objectives: The initiative for this study was based on the lack of common guidelines for diagnostic procedures and for treatment of HNCUP patients in the Nordic countries constituting a region having a rather homogeneous population.Method: A structured questionnaire was sent to all university hospitals in the five Nordic countries.Results: Four of the five Nordic countries use either national guidelines or specific protocols when handling HNCUP. The main diagnostic tools are PET-CT, fine needle aspiration, endoscopic evaluation with biopsies, and most often bilateral tonsillectomy. At 21 of 22 university hospitals the treatment decision is made at a multidisciplinary conference. Three of seven Swedish centres use only radiotherapy or chemoradiotherapy to treat N+ HNCUP patients. Robotic surgery for biopsy of the tongue base is beginning to become an alternative to targeted biopsies in Sweden and Finland. Narrow Band Imaging is used only in Finland.

  • 17.
    Farnebo, Lovisa
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Dept Otorhinolaryngol, Linkoping, Sweden..
    Malila, Nea
    Finnish Canc Registry, FIN-00170 Helsinki, Finland..
    Makitie, Antti
    Karolinska Inst, Div Ear Nose & Throat Dis Intervent & Technol, Dept Clin Sci, Stockholm, Sweden.;Karolinska Hosp, S-10401 Stockholm, Sweden.;Univ Helsinki, Dept Otorhinolaryngol Head & Neck Surg, Helsinki, Finland.;Helsinki Univ Hosp, FI-00029 Helsinki, Hus, Finland..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Early death among head and neck cancer patients2016In: Current Opinion in Otolaryngology & Head and Neck Surgery, ISSN 1068-9508, E-ISSN 1531-6998, Vol. 24, no 2, 115-120 p.Article, review/survey (Refereed)
    Abstract [en]

    Purpose of reviewManagement of advanced head and neck cancer (HNC) is characterized by high mortality. Furthermore, the treatment involves significant burden to patients and high costs to healthcare systems. Recognizing the risks of early death in patients with a high probability of noncurable disease is important for each individual treatment decision-making. It is thus critical to consider the benefits and side-effects of the planned treatment in relation to the expected survival and to discuss these factors with the patient. However, only few studies have documented early death in HNC patients, that is, during the first posttreatment 6 months. We performed a systematic literature review to find the incidence of this phenomenon and to outline the probable cause.Recent findingsEarly mortality in patients with HNC can be explained either by direct effect of malignant disease, may be related to comorbidities, or secondary to the treatment. These factors act together resulting in expected or unexpected early death.SummaryThe present review provides information on the mechanisms leading to early phase mortality (<6 months) after management of HNC. It also reports the incidence of this phenomenon among Finnish and Swedish patient populations.

  • 18.
    Fransson, Anette E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kisiel, Marta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Pirttilä, Kristian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Pettersson, Curt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Videhult Pierre, Pernilla
    Division of Audiology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hydrogen Inhalation Protects against Ototoxicity Induced by Intravenous Cisplatin in the Guinea Pig2017In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 11, 280Article in journal (Refereed)
    Abstract [en]

    Introduction: Permanent hearing loss and tinnitus as side-effects from treatment with the anticancer drug cisplatin is a clinical problem. Ototoxicity may be reduced by co-administration of an otoprotective agent, but the results in humans have so far been modest.

    Aim: The present preclinical in vivo study aimed to explore the protective efficacy of hydrogen (H2) inhalation on ototoxicity induced by intravenous cisplatin.

    Materials and Methods: Albino guinea pigs were divided into four groups. The Cispt (n = 11) and Cispt+H2 (n = 11) groups were given intravenous cisplatin (8 mg/kg b.w., injection rate 0.2 ml/min). Immediately after, the Cispt+H2 group also received gaseous H2 (2% in air, 60 min). The H2 group (n = 5) received only H2 and the Control group (n = 7) received neither cisplatin nor H2. Ototoxicity was assessed by measuring frequency specific ABR thresholds before and 96 h after treatment, loss of inner (IHCs) and outer (OHCs) hair cells, and by performing densitometry-based immunohistochemistry analysis of cochlear synaptophysin, organic transporter 2 (OCT2), and copper transporter 1 (CTR1) at 12 and 7 mm from the round window. By utilizing metabolomics analysis of perilymph the change of metabolites in the perilymph was assessed.

    Results: Cisplatin induced electrophysiological threshold shifts, hair cell loss, and reduced synaptophysin immunoreactivity in the synapse area around the IHCs and OHCs. H2 inhalation mitigated all these effects. Cisplatin also reduced the OCT2 intensity in the inner and outer pillar cells and in the stria vascularis as well as the CTR1 intensity in the synapse area around the IHCs, the Deiters' cells, and the stria vascularis. H2 prevented the majority of these effects.

    Conclusion: H2 inhalation can reduce cisplatin-induced ototoxicity on functional, cellular, and subcellular levels. It is proposed that synaptopathy may serve as a marker for cisplatin ototoxicity. The effect of H2 on the antineoplastic activity of cisplatin needs to be further explored.

  • 19.
    Hellberg, Victoria
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Gahm, Caroline
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ehrsson, Hans
    Karolinska Univ Hosp, Karolinska Pharm, Stockholm, Sweden..
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    In Response to Immunohistochemical Localization of OCT2 in the Cochlea of Various Species2016In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, no 6, E232-E232 p.Article in journal (Refereed)
  • 20.
    Hellberg, Victoria
    et al.
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
    Gahm, Caroline
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ehrsson, Hans
    Karolinska Univ Hosp, Karolinska Pharm, S-14186 Stockholm, Sweden..
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Immunohistochemical localization of OCT2 in the cochlea of various species2015In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 125, no 9, E320-E325 p.Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo locate the organic cation transporter 2 (OCT2) in the cochlea of three different species and to modulate the ototoxicity of cisplatin in the guinea pig by pretreatment with phenformin, having a known affinity for OCT2. Study DesignImmunohistochemical and in vivo study. MethodsSections from the auditory end organs were subjected to immunohistochemical staining in order to identify OCT2 in cochlea from untreated rats, guinea pigs, and a pig. In the in vivo study, guinea pigs were given phenformin intravenously 30 minutes before cisplatin administration. Electrophysiological hearing thresholds were determined, and hair cells loss was assessed 96 hours later. The total amount of platinum in cochlear tissue was determined using mass spectrometry. ResultsOrganic cation transporter 2 was found in the supporting cells and in type I spiral ganglion cells in the cochlea of all species studied. Pretreatment with phenformin did not reduce the ototoxic side effect of cisplatin. Furthermore, the concentration of platinum in the cochlea was not affected by phenformin. ConclusionsThe localization of OCT2 in the supporting cells and type I spiral ganglion cells suggests that this transport protein is not primarily involved in cisplatin uptake from the systemic circulation. We hypothesize that OCT2 transport intensifies cisplatin ototoxicity via transport mechanisms in alternate compartments of the cochlea. Level of EvidenceN/A. Laryngoscope, 125:E320-E325, 2015

  • 21. Hellberg, Victoria
    et al.
    Wallin, Inger
    Ehrsson, Hans
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Cochlear Pharmacokinetics of Cisplatin: An In Vivo Study in the Guinea Pig2013In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 123, no 12, 3172-3177 p.Article in journal (Refereed)
    Abstract [en]

    Objectives/HypothesisCisplatin produces toxic lesions to outer hair cells (OHCs) in the cochlear base but not in the apex. The objective of this study was to compare the pharmacokinetic profile of cisplatin in scala tympani (ST) perilymph in the cochlear base and apex, respectively. Study DesignIn vivo animal study. MethodsForty-seven guinea pigs were given an intravenous bolus injection of an ototoxic dose of cisplatin. Ten to 240 minutes after cisplatin was given, blood, cerebrospinal fluid (CSF), and ST perilymph were aspirated within the same target time. ST perilymph was aspirated from the basal turn and from the apex of the cochlea by two different sampling techniques. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the parent drug. ResultsTen minutes after administration, the concentration of cisplatin in ST perilymph was 4-fold higher in the basal turn of the cochlea than in the apex. At 30 minutes, the drug concentrations did not differ. At 60 minutes, the level of cisplatin in ST perilymph and blood UF was equivalent. The perilymph-blood ratio increased thereafter with time. ConclusionThe pharmacokinetic findings of an early high concentration of cisplatin in the base of the cochlea and delayed elimination of cisplatin from ST perilymph compared to blood might correlate to the cisplatin-induced loss of OHCs in the base of the cochlea. Level of EvidenceN/A. Laryngoscope, 123:3172-3177, 2013

  • 22. Isaksson, Joakim
    et al.
    Salander, Par
    Granstrom, Brith
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Critical Incidents Reveal How Patients with Head and Neck Cancer Construct Their "Secure Base" as a "Helping System"2014In: Journal of psychosocial oncology, ISSN 0734-7332, E-ISSN 1540-7586, Vol. 32, no 3, 322-341 p.Article in journal (Refereed)
    Abstract [en]

    Most studies of the psychosocial needs of patients with head and neck cancers (HNC) use predefined categories and explicitly ask for specified needs. These studies are important but should be complemented with inductive studies based on patients' own descriptions of experiences. This qualitative study is such a contribution. In repeated interviews positive and negative incidents were collected from 137 patients with HNC, and these experiences were categorized in dimensions expressing needs. A core category-"being included-neglected by a helping system"-emerged from the narrated incidents and was based on the dimensions engagement, competence, and information. The findings are easily related to attachment theory by stressing the significance of establishing trustful relationships with the health care staff, as attachment figures, who respond flexibly and sensitively to the patient's needs. In the constitution of health care as a helping system, all encounters between the patient and health care staff matters. Further research should preferably focus on the creation of guidelines for the constitution of health care as a helping system, that is, how the found factors of a helping system can be operationalized in clinical practice.

  • 23. Isaksson, Joakim
    et al.
    Salander, Par
    Granstrom, Brith
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Patients With Head and Neck Cancer Narrate the Importance of Being Included in a Helping System2013In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 22, no SI3, 63-63 p.Article in journal (Other academic)
  • 24.
    Isaksson, Joakim
    et al.
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Salander, Par
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Lilliehorn, Sara
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden.;Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Living an everyday life with head and neck cancer 2-2.5 years post-diagnosis - A qualitative prospective study of 56 patients2016In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 154, 54-61 p.Article in journal (Refereed)
    Abstract [en]

    Rationale: There are many studies available describing how patients are affected by head and neck cancer (HNC) and its treatment. Usually these studies are quantitative and focus on assessing patients' quality of life or distress post-treatment. These studies are important, but they are of limited value if we are interested in understanding more about HNC in an everyday life context. Objective: The purpose was to determine how life was lived and valued during and after treatment for HNC and to detect different transitions in returning to everyday life. Methods: During 2009-2012, 56 patients with HNC were consecutively included, and interviewed at 6, 12, and 24 months post-treatment about how they lived their lives. All patients received primary treatment at a tertiary referral university hospital in Sweden. Results: Four different trajectories and transitions emerged. The first group (n = 15) evaluated their illness experience as a past parenthesis in their life suggesting that they had psychologically left the illness behind. In the second group (n = 9), the impact of the disease seemed to be diluted by other strains in their life, and although these patients to some extent were still hampered by side effects, they regarded them as `no big deal'. The cancer really made a difference in the third group (n = 12) in both positive and negative ways and seemed to reflect a balance between such effects. In the fourth group (n = 20), the physical and/or psychological problems predominated and the patients' lives had changed for the worse. Conclusion: The narratives showed that being afflicted by HNC has different impacts depending on how the patients live their lives it is a matter of individual transition in an everyday life context. This idiosyncrasy challenges the meaningfulness of screening efforts to identify vulnerable groups for psychosocial intervention.

  • 25. Isaksson, Joakim
    et al.
    Salander, Par
    Lilliehorn, Sara
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Impact of Head and Neck Cancer on Living an Everyday Life 2 Years Post-treatment - A Qualitative Prospective Study2015In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 24, no S2, 256-257 p., P2-52Article in journal (Other academic)
  • 26.
    Isaksson, Joakim
    et al.
    Umeå Univ, Dept Social Work, Umeå, Sweden..
    Salander, Pär
    Umeå Univ, Dept Social Work, Umeå, Sweden..
    Lilliehorn, Sara
    Umeå Univ, Dept Social Work, Umeå, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala Univ, Dept Surg Sci Othorinolaryngol & Head & Neck Surg, Uppsala, Sweden..
    Different transitions in returning to everyday life for patients with head and neck cancer - a qualitative prospective study2016In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 25, no SP. S3, 95-95 p.Article in journal (Other academic)
  • 27.
    Isaksson, Joakim
    et al.
    Umea Univ, Dept Social Work, SE-90187 Umea, Sweden.
    Wilms, Torben
    Umea Univ, Dept Med Biosci, SE-90187 Umea, Sweden;Umea Univ, Dept Clin Sci Otorhinolaryngol, SE-90187 Umea, Sweden.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Fransson, Per
    Ehrsson, Ylva Tiblom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Meaning of work and the process of returning after head and neck cancer2015In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 24, no 1, 205-213 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purposes of this study were (1) to investigate employment status at diagnosis, sick leave, and returning to work patterns in correlation to quality of life, anxiety, and depression in patients treated for head and neck cancer (HNC) and (2) to explore patients' experiences of the process of returning to work.

    METHODS: Sixty-six patients with HNC (aged 34-66 years) were repeatedly interviewed over a period of 24 months. Interview responses that concerned the patients' experiences and ideas about work were categorised using the similarities-differences technique. Questionnaires on quality of life, anxiety, and depression were used to describe the patient characteristics and the differences between groups.

    RESULTS: In total, 53 % of the patients had returned to work at 24 months after treatment, and 17 % were deceased. Several quality of life parameters were significantly worse for patients not working at 24 months after treatment. Nine categories were found to describe the return-to-work process starting with symptoms causing sick leave, thoughts about the sick leave, and ending with the return to work and/or retirement.

    CONCLUSIONS: Returning to work is an important part of life because it structures everyday life and strengthens the individual's identity. The quality of life results showed significant differences between workers and non-workers at the 24-month follow-up. The patients need to be both physically and mentally prepared for the process of returning to work. It is important to take an individual rehabilitation approach to guide and support the patients in returning to work and regaining an important aspect of their everyday life. In such an approach, it is vital to understand the patients' overall life context and the patients' own perspective on the process and meaning associated with work.

  • 28.
    Jonsson, Eva Lindell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nylander, Karin
    Hallén, Lars
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Effect of radiotherapy on expression of hyaluronan and EGFR and presence of mast cells in squamous cell carcinoma of the head and neck.2012In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 4, no 6Article in journal (Refereed)
    Abstract [en]

    Head and neck squamous cell carcinoma is a common form of cancer, and despite improvements in treatment during the last decades, survival rates have not significantly increased. There is therefore a need to better understand how these tumours and the adjacent tissues react to radiotherapy, the most common type of treatment for this group of tumours. In order to improve this understanding, the expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) and the presence of mast cells were mapped before and after radiotherapy using immunohistochemistry. The results showed HA and EGFR to have similar expression patterns in tumour tissue and histologically normal squamous epithelium prior to radiotherapy. Following radiotherapy, EGFR increased in histologically normal epithelium. An increased number of mast cells were also observed as a result of radiotherapy. No expression of EGFR was observed in the connective tissue either prior to or following radiotherapy.

  • 29.
    Jonsson, Eva Lindell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nylander, Karin
    Umea Univ, Dept Med Biosci, Umea, Sweden.
    Hallén, Lars
    Umea Univ, Dept Clin Sci, Umea, Sweden.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N02017In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 8, 877-882 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether the extent of expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) in squamous cell carcinoma of the mobile tongue can predict the risk of cervical metastasis and survival. Study design: Retrospective histopathologic study. Methods: Surgical specimens from 64 patients who had undergone surgery for squamous cell carcinoma of the mobile tongue were assessed using immunohistochemistry to investigate the expression of HA and EGFR in the primary tumours, and the data were then correlated to cervical metastasis and survival. Results: There was a significant correlation between the intensity of HA staining and patient survival (p .024), and a weak correlation between the staining proportion of EGFR and the risk for regional recurrence (AUC 66). Conclusions: This study indicates that immunoscoring using HA could be used to provide prognostic tools for tongue cancer, and that it might be of interest to study the prognostic properties of EGFR further concerning the risk for regional recurrence after the primary treatment.

  • 30. Kreimer, Aimée R
    et al.
    Johansson, Mattias
    Waterboer, Tim
    Kaaks, Rudolf
    Chang-Claude, Jenny
    Drogen, Dagmar
    Tjønneland, Anne
    Overvad, Kim
    Quirós, J Ramón
    González, Carlos A
    Sánchez, Maria José
    Larrañaga, Nerea
    Navarro, Carmen
    Barricarte, Aurelio
    Travis, Ruth C
    Khaw, Kay-Tee
    Wareham, Nick
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Peeters, Petra H M
    Panico, Salvatore
    Masala, Giovanna
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, H Bas
    Laurell, Göran
    Umeå University, Umeå, Sweden.
    Hallmans, Göran
    Manjer, Jonas
    Ekström, Johanna
    Skeie, Guri
    Lund, Eiliv
    Weiderpass, Elisabete
    Ferrari, Pietro
    Byrnes, Graham
    Romieu, Isabelle
    Riboli, Elio
    Hildesheim, Allan
    Boeing, Heiner
    Pawlita, Michael
    Brennan, Paul
    Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 21, 2708-2715 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.

    METHODS:

    We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.

    RESULTS:

    HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.

    CONCLUSION:

    HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

  • 31.
    Kämpfe Nordström, Charlotta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Human Vestibular Aqueduct: Anatomical Characteristics and Enlargement Criteria2016In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 37, no 10, 1637-1645 p.Article in journal (Refereed)
    Abstract [en]

    Hypothesis: The human vestibular aqueduct (VA) shows great anatomical variations, and imaging can be difficult, so we need more data on the normal anatomy of the VA for better radiologic evaluation of large vestibular aqueduct syndrome (LVAS). Background: The normal anatomy of the human VA was analyzed in micro-dissected human temporal bones. Methods: The study is based on two sets of human temporal bones. One set of 32 human temporal bones was selected from a collection of 50 micro-dissected specimens. The outline of the intraosseous portion of the VA was drawn and digitized, and dimensions were assessed. The other set of 20 plastic molds were randomly selected from a collection of 324 specimens, and the VA dimensions were assessed. Results: Measurements from this study are presented in means, standard deviations, and ranges. The results from these measurements are considered normal and compared with previously published data. The variations in the normal anatomy of the VA are presented and discussed. Conclusion: The VA courses sagittal in the human skull. Therefore, we recommend the lateral projection (reformatted) to demonstrate the VA in LVAS patients. We advocate assessing: 1) the width (or height) of the external aperture (EA), 2) the width at the half distance between the EA and the common crus (CC), and if possible 3) the width of the proximal portion of the VA. Based on the measurements, our criteria for enlargement are 2.0mm or greater, 1.5mm or greater, and more than 1mm at these sites.

  • 32. Lindblom, Ulrika
    et al.
    Garskog, Ola
    Kjellen, Elisabeth
    Laurell, Goran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jaghagen, Eva Levring
    Wahlberg, Peter
    Zackrisson, Bjorn
    Nilsson, Per
    Radiation-induced trismus in the ARTSCAN head and neck trial2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 5, 620-627 p.Article in journal (Refereed)
    Abstract [en]

    Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patient's oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose-response relationship for trismus. Material and methods. Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21-127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite (R) range of motion scale was used to measure maximal interincisal distance. The dose-response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. Results. No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose-response fit to the endpoint data was found for the dose to the ipsilateral masseter. Conclusions. Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensity-modulated radiation therapy will reduce problems with trismus.

  • 33.
    Lindblom, Ulrika
    et al.
    Lund Univ, Dept Clin Sci Oncol & Radiat Phys, S-22100 Lund, Sweden.;Kirkenes Hosp, Dept Otorhinolaryngol, Kirkenes, Norway..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Garskog, Ola
    Umea Univ, Dept Clin Sci, Otorhinolaryngol, SE-90187 Umea, Sweden..
    Kjellen, Elisabeth
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Dept Clin Sci, Otorhinolaryngol, SE-90187 Umea, Sweden..
    Wahlberg, Peter
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Otorhinolaryngol, S-22100 Lund, Sweden..
    Zackrisson, Bjorn
    Umea Univ, Dept Radiat Sci, Oncol, SE-90187 Umea, Sweden..
    Jaghagen, Eva Levring
    Umea Univ, Dept Odontol Oral & Maxillofacial Radiol, SE-90187 Umea, Sweden..
    Aspiration as a late complication after accelerated versus conventional radiotherapy in patients with head and neck cancer2016In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, no 3, 304-311 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion Neck dissection after radiotherapy increased the risk of aspiration as a late effect in a sub-sample of patients treated for head and neck cancer in the ARTSCAN study. Patients treated with accelerated fractionation (AF) developed aspiration, with or without coughing, more frequently than patients treated with conventional fractionation (CF). Objectives A long-term follow-up study was conducted to determine the frequency of aspiration as a late effect in patients with head and neck cancer treated with AF or CF. Method One-hundred and eight patients were recruited from two centres of the Swedish multi-centre study, ARTSCAN, where AF and CF were compared. Patients with positive lymph nodes were treated with neck dissection after completing radiotherapy. The follow-up was performed at a median of 65 months after initiation of radiotherapy and included an ENT and a videofluoroscopic examination. Results Aspiration was found in 51/108 (47%) and silent aspiration in 34/96 (35%) patients. Neck dissection (n = 47 patients) was significantly associated with both aspiration and silent aspiration. Aspiration was more common among patients treated with AF (34/61; 56%) compared to CF (17/47; 36%; p = 0.053). Silent aspiration was also more common after AF (24/54; 44%) than after CF (10/42; 24%; p = 0.052).

  • 34.
    Liu, Wei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Blom, Hans
    Royal Inst Technol, Dept Appl Phys, Sci Life Lab, Tomtebodavagen 23A, S-17121 Solna, Sweden..
    Magnusson, Peetra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Schrott-Fischer, Annelies
    Med Univ Innsbruck, Dept Otolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Glueckert, Rudolf
    Med Univ Innsbruck, Dept Otolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Santi, Peter A.
    Univ Minnesota, Dept Otolaryngol, 121 Lions Res Bldg,2001 Sixth St SE, Minneapolis, MN 55455 USA..
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea: the Connexin26/30 proteins are separately expressed in man2016In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 365, no 1, 13-27 p.Article in journal (Refereed)
    Abstract [en]

    Globally 360 million people have disabling hearing loss and, of these, 32 million are children. Human hearing relies on 15,000 hair cells that transduce mechanical vibrations to electrical signals in the auditory nerve. The process is powered by the endo-cochlear potential, which is produced by a vascularized epithelium that actively transports ions in conjunction with a gap junction (GJ) system. This "battery" is located "off-site" in the lateral wall of the cochlea. The GJ syncytium contains the GJ protein genes beta 2 (GJB2/connexin26 (Cx26)) and 6 (GJB6/connexin30 (Cx30)), which are commonly involved in hereditary deafness. Because the molecular arrangement of these proteins is obscure, we analyze GJ protein expression (Cx26/30) in human cochleae by using super-resolution structured illumination microscopy. At this resolution, the Cx26 and Cx30 proteins were visible as separate plaques, rather than being co-localized in heterotypic channels, as previously suggested. The Cx26 and Cx30 proteins thus seem not to be co-expressed but to form closely associated assemblies of GJ plaques. These results could assist in the development of strategies to treat genetic hearing loss in the future.

  • 35.
    Loizou, Christos
    et al.
    Umea Univ, Dept Clin Sci, Div Otorhinolaryngol, SE-90185 Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Dept Clin Sci, Div Otorhinolaryngol, SE-90185 Umea, Sweden..
    Arvidsson, Andreas
    Umea Univ, Dept Clin Sci, Div Otorhinolaryngol, SE-90185 Umea, Sweden..
    Lindquist, David
    Umea Univ, Dept Radiat Sci, Div Oncol, SE-90185 Umea, Sweden..
    Nylander, Karin
    Umea Univ, Dept Med Biosci, Div Pathol, SE-90185 Umea, Sweden..
    Olofsson, Katarina
    Umea Univ, Dept Clin Sci, Div Otorhinolaryngol, SE-90185 Umea, Sweden..
    Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance2015In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 10, 1058-1064 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion: Recurrent respiratory papillomatosis (RRP) patients with high surgical treatment frequency (>= 1/year, HF) were significantly younger and had a more widespread laryngeal disease compared to a low frequency treated group (< 1 treatment/year, LF). This study confirms the existence of a clinical RRP group, not primarily related to HPV sub-type, but more care-intensive and in need of more vigilant follow-up. Objectives: RRP is associated with high morbidity due to its influence on breathing and voice. The purpose of this study was to characterize RRP patients in northern Sweden and investigate possible predictor factors affecting therapeutic needs. Method: Patients from the regional referral area (northern Sweden) were categorized for age, disease duration, juvenile or adult onset, profile of disease development, number of surgical sessions in relation to disease duration, laryngeal deposition of papilloma, gender, and HPV sub-types, in order to identify patients with increased need for frequent surgical treatment. Results: The median age of the RRP patients (n = 48) was 44.5 years; 34 (71%) were males and 14 (29%) females, most were infected with HPV 6. Patients with high surgical treatment frequency/year were significantly younger and showed more widespread papillomatous vegetation in the larynx, compared to the low frequency treated group.

  • 36.
    Loizou, Christos
    et al.
    Umea Univ, Div Otorhinolaryngol, Dept Clin Sci, S-90185 Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Div Otorhinolaryngol, Dept Clin Sci, S-90185 Umea, Sweden..
    Lindquist, David
    Umea Univ, Div Oncol, Dept Radiat Sci, S-90185 Umea, Sweden..
    Ofverman, Charlotte
    Umea Univ, Div Oncol, Dept Radiat Sci, S-90185 Umea, Sweden..
    Stefansson, Kristina
    Umea Univ, Div Oncol, Dept Radiat Sci, S-90185 Umea, Sweden..
    Nylander, Karin
    Umea Univ, Div Pathol, Dept Med Biosci, S-90185 Umea, Sweden..
    Olofsson, Katarina
    Umea Univ, Div Otorhinolaryngol, Dept Clin Sci, S-90185 Umea, Sweden..
    Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus2015In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 10, no 6, 3565-3572 p.Article in journal (Refereed)
    Abstract [en]

    The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2-fold increase between 1990 and 2013; specifically, a 2.7-fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV-positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.

  • 37. Loizou, Christos
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lindquist, David
    Olofsson, Katarina
    Voice and quality of life in patients with recurrent respiratory papillomatosis in a northern Sweden cohort2014In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 4, 401-406 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion:

    The frequency of operations, age at onset, gender and subtype of the human papilloma virus (HPV) may be used as factors to predict voice disability.

    Objectives:

    Patients with recurrent respiratory papillomatosis (RRP) are characterized by morbid consequences due to a lifelong repetitive influence on voice and breathing ability and the need for recurrent surgical treatments. The aim of the study was to measure the quality of voice and life using evaluated and validated questionnaires in a northern Sweden RRP population.

    Methods:

    A total of 27 consecutive patients with RRP (age 21-71 years, median 47 years) were evaluated 3 months postoperatively (CO2 laser treatment) using the voice handicap index (VHI) and SF-36 questionnaires to assess the impact on life and voice in an RRP population. The values were compared to historical normative data, VHI ≤ 20.

    Results:

    Patients that underwent more than one operation per year were younger (p = 0.028) than those treated less frequently. The mean VHItotal score in patients with RRP was 39.3, indicating a statistically significant impairment of voice quality (p < 0.001) as compared with normal subjects. Voice dysfunction was observed in 21 patients (78%). Significantly lower values than the normal population regarding the quality of life in patients with RRP were obtained in the domain of social functioning (p = 0.029). Females, patients with frequent surgical treatment sessions and patients with the high-risk HPV types scored significantly lower in several domains of the quality of life assessment as compared with normal subjects. The results should be interpreted with caution due to the limited number of subjects.

  • 38. Loljung, Lotta
    et al.
    Coates, Philip J
    Nekulova, Marta
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wahlgren, Magnus
    Wilms, Torben
    Widlöf, Mikael
    Hansel, Anna
    Nylander, Karin
    High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue2014In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 43, no 1, 14-19 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    p63 proteins are important in formation of the oral mucosa. Normal oral mucosa shows a balance between the six protein isoforms, whereas an imbalance between them is seen in squamous cell carcinomas (SCC). There is controversy over the clinical impact of p63 in SCC, which may relate to different expression in different areas. In addition, p63 isoforms can act as p53-like molecules (TAp63) or can inhibit p53 functions (ΔNp63) and expression of these isoforms varies in different tumours. Here, we chose to concentrate on the most common intra-oral sub-site, SCC of the mobile tongue.

    METHODS:

    Total p63, ΔNp63 and TAp63 were analysed separately using immunohistochemistry. The percentage of cells and intensity of expression of different isoforms of p63 was evaluated using a quick score method and correlated with clinical data in a group of 87 patients with tongue SCC.

    RESULTS:

    All tumours expressed p63 in at least 60% of the cells when using two different antibodies detecting all 6 isoforms. p63 expression correlated significantly with 2-year survival (P = 0.018), with fewer patients surviving 2 years if their tumours expressed p63 with strong intensity in at least 80% of the cells (quick score 18). Looking at 5-year survival, this was even more emphasized. ΔNp63 was expressed in all tumours, whereas expression of TAp63 was seen only in 59/87 patients, usually at very low levels.

    CONCLUSIONS:

    Based on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.

  • 39.
    Nyqvist, Johanna
    et al.
    Skane Univ Hosp, Dept Otolaryngol & Head & Neck Surg, Lund, Sweden.;Umea Univ, Dept Clin Sci Otolaryngol & Head & Neck Surg, S-90187 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, S-90187 Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Dept Clin Sci Otolaryngol & Head & Neck Surg, S-90187 Umea, Sweden..
    Hammerlid, Eva
    Sahlgrens Univ Hosp, Dept Otolaryngol & Head & Neck Surg, Gothenburg, Sweden..
    Kjellen, Elisabeth
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Franzen, Lars
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Soderstrom, Karin
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Wickart-Johansson, Gun
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Friesland, Signe
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Sjodin, Helena
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Brun, Eva
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Ask, Anders
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Ekberg, Lars
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Bjork-Eriksson, Thomas
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Nyman, Jan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Loden, Britta
    Karlstad Cent Hosp, Dept Clin Oncol, Karlskrona, Sweden..
    Lewin, Freddi
    Ryhov Cty Hosp, Dept Oncol, Jonkoping, Sweden..
    Reizenstein, Johan
    Orebro Univ Hosp, Dept Oncol, Orebro, Sweden..
    Lundin, Erik
    Ryhov Cty Hosp, Dept Oncol, Jonkoping, Sweden..
    Zackrisson, Bjorn
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 118, no 2, 335-341 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.

  • 40. Ottosson, Sandra
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Olsson, Cecilia
    The experience of food, eating and meals following radiotherapy for head and neck cancer: a qualitative study2013In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 22, no 7-8, 1034-1043 p.Article in journal (Refereed)
    Abstract [en]

    Aims and objectives To describe the experience of food, eating and meals following radiotherapy in patients with head and neck cancer. Background Eating problems are common in patients with head and neck cancer and may remain for a long period of time after treatment. Design A qualitative study design using in-depth semi-structured interviews. Methods Interviews were conducted nine months after the termination of radiotherapy. A purposive sample of thirteen patients with head and neck cancer participated in the study. The interviews were tape-recorded, transcribed verbatim and analysed using content analysis. Results The experience of food, eating and meals up to nine months after radiotherapy was captured in six categories: A long journey taking small steps to an uncertain future', A new way of eating', Eating without satisfaction', Challenging meals outside the family', Support and information the key to a successful journey' and The creation and acceptance of a new normal'. Conclusion This study provides new information on the long-term aspects of food, eating and meals in patients with head and neck cancer. Head and neck cancer signifies a long journey with problems affecting physical, psychological and social aspects of food. Information and support and the use of strategies are important for patients with head and neck cancer to adapt to new possibilities for living after cancer treatment. Relevance to clinical practice All members of the multiprofessional team need to be aware of the struggles with food and eating experienced by patients with head and neck cancer during the convalescent period. It is therefore important that the follow-up focuses on all aspects of food, eating and meals as a part of a holistic approach.

  • 41. Ottosson, Sandra
    et al.
    Lindblom, Ulrika
    Wahlberg, Peter
    Nilsson, Per
    Kjellen, Elisabeth
    Zackrisson, Bjorn
    Jaghagen, Eva Levring
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Weight loss and body mass index in relation to aspiration in patients treated for head and neck cancer: a long-term follow-up2014In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 22, no 9, 2361-2369 p.Article in journal (Refereed)
    Abstract [en]

    Persistent severe swallowing dysfunction with aspiration is a common and sometimes overlooked sequelae after treatment for squamous cell carcinoma of the head and neck (SCCHN) and may impact food intake and nutritional status. More knowledge is needed to increase the understanding of severe swallowing dysfunction as a risk factor for persistent nutritional deteriorations in SCCHN survivors. The purpose of the study was to investigate weight loss and body mass index (BMI) in relation to pharyngeal swallowing function in a long-term perspective in patients after SCCHN treatment. Data from 101 patients were available for the analyses. Swallowing function was assessed by videofluoroscopy at a mean of 71.6 months after the start of radiotherapy (RT). Percent weight change (calculated with weight at the start of RT as the reference) and BMI at follow-up were the primary nutritional measures. Aspiration was present in 48 of 101 patients (48 %). Patients with aspiration had a significantly higher mean weight loss and a lower BMI (-10.9 % and 23.1, respectively) at follow-up compared with patients without aspiration (-2.8 % and 26.0, respectively). Patients with aspiration were unable to gain weight after 23 months. Only ten of 101 patients (10 %) were underweight at follow-up. Swallowing dysfunction with aspiration was related to long-term weight loss and reduced BMI. Few patients were underweight despite the high prevalence of swallowing dysfunction.

  • 42. Ottosson, Sandra
    et al.
    Soderstrom, Karin
    Kjellen, Elisabeth
    Nilsson, Per
    Zackrisson, Bjorn
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study2014In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 9, 160- p.Article in journal (Refereed)
    Abstract [en]

    Background: Weight loss is a common problem in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims of the present study were to determine if treated volume (TV), as a measure of the radiation dose burden, can predict weight loss in patients with oropharyngeal cancer and to analyze weight loss and body mass index (BMI) in the same patient group in relation to 5-year overall survival. Methods: The ARTSCAN trial is a prospective, randomized, multicenter trial in patients with SCCHN. Nutritional data from the ARTSCAN trial were analyzed retrospectively using univariate and multivariate statistical methods based on information on percentage weight loss from the start of RT up to five months after the termination of RT (study cohort 1, n = 232) and information on patients' BMI at the start of RT (study cohort 2, n = 203). TV was defined as the volume of the patient receiving at least 95% of the prescribed dose. TV64.6 (Gy) encompasses macroscopic tumor and TV43.7 (Gy) elective lymph nodes of the neck. Results: TV64.6 Gy and TV43.7 Gy were both significantly correlated with higher weight loss up to five months after the termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT was shown to be a prognostic factor for 5-year overall survival in study cohort 2 but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78 (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight, respectively. Conclusions: TV can predict weight loss during RT in patients with oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m(2)) at the start of RT is positively associated with survival in patients with oropharyngeal cancer.

  • 43. Ottosson, Sandra
    et al.
    Zackrisson, Björn
    Kjellén, Elisabeth
    Nilsson, Per
    Laurell, Göran
    Department of Clinical Sciences, Otorhinolaryngology, Umeå University, Umeå , Sweden.
    Weight loss in patients with head and neck cancer during and after conventional and accelerated radiotherapy2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, 711-718 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Weight loss is common among patients with squamous cell carcinoma of the head and neck (SCCHN) and is mainly due to tumor and treatment related factors. The aim of the present study was to evaluate weight loss in patients with SCCHN undergoing two different radiotherapy (RT) schedules.

    MATERIAL AND METHODS:

    Nutritional data were analyzed from the ARTSCAN study, a controlled randomized prospective Swedish multicenter study conducted with the aim of comparing conventional fractionation (2.0 Gy per day, total 68 Gy during 7 weeks) and accelerated fractionation (1.1 + 2.0 Gy per day, total 68 Gy during 4.5 weeks). Seven hundred and fifty patients were randomized and 712 patients were followed from the start of RT in the present nutritional study.

    RESULTS:

    The patients had a weight loss of 11.3% (± 8.6%) during the acute phase (start of RT up to five months after the termination of RT). No difference in weight loss was seen between the two RT fractionation schedules (p = 0.839). Three factors were significantly predictive for weight loss during the acute phase, i.e. tumor site, overweight/obesity or lack of tube feeding at the start of RT. Moreover, the nadir point of weight loss occurred at five months after the termination of RT.

    CONCLUSION:

    The results of the present study showed no difference in weight loss between the two RT fractionation schedules and also highlight that weight loss in SCCHN is a multifactorial problem. Moreover, the nadir of weight loss occurred at five months after the termination of treatment which calls for more intense nutritional interventions during the period after treatment.

  • 44. Rentoft, Matilda
    et al.
    Coates, Philip John
    Loljung, Lotta
    Wilms, Torben
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nylander, Karin
    Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue2014In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 35, no 5, 4194-4198 p.Article in journal (Refereed)
    Abstract [en]

    Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81 % for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42 % to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue.

  • 45. Salander, Par
    et al.
    Isaksson, Joakim
    Granstrom, Brith
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    How Patients Make use of a Specialist Nurse Function in Head and Neck Cancer: An Empirical Study2014In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 23, no 3, 159-159 p.Article in journal (Other academic)
  • 46.
    Salander, Pär
    et al.
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Isaksson, Joakim
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Granström, Brith
    Umea Univ, Dept Clin Sci Otorhinolaryngol, Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala Univ, Dept Surg Sci Otolaryngol & Head & Neck Surg, Uppsala, Sweden..
    Motives that head and neck cancer patients have for contacting a specialist nurse - an empirical study2016In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 25, no 21-22, 3160-3166 p.Article in journal (Refereed)
    Abstract [en]

    Aims and objectives. The purpose of this study is to systematically explore the motives for patients with head and neck cancer to contact a specialist nurse during two years postdiagnosis. Background. Research focusing on the role of specialist nurses in cancer care almost exclusively concern cancers other than head and neck cancer. Design. Qualitative, descriptive study based on the contacts between patients with head and neck cancer and a specialist nurse. Methods. Patients were invited to contact a specialist nurse by telephone. The specialist nurse took systematic field notes, that is, she registered who contacted her, the nature of the call and the outcome. Sixty patients were included. Results. In descending order, the motives for contact were questions about practical and uncomplicated matters, consultations about medical troubles/worries, presenting a report of the patient's situation, requests for additional information about the treatment plan and requests for medical information. The pattern of the patients' motivations for calling was not related to medical or social factors, suggesting that the initiative to make contact is very much a question of the complexity of individual life circumstances. Very few referrals were sent from the specialist nurse to other professionals. Conclusions. The specialist nurse turned out to be more than just a coordinator of health-care resources. The findings bring up questions about the potential of the nurse's function as a coordinator, but also as a potential attachment figure, and questions about the nurse's relationships to other professionals. Relevance to clinical practice. When implementing a specialist nurse function, it is important to decide whether the function should be inspired by a broader relational perspective. In addition to the indispensible competence and experience in the clinical field of head and neck cancer, training in counselling and acquaintance with object-relational psychology will then be desirable.

  • 47. Sgaramella, N.
    et al.
    Coates, P. J.
    Strindlund, K.
    Loljung, L.
    Colella, G.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rossiello, R.
    Muzio, L. L.
    Loizou, C.
    Tartaro, G.
    Olofsson, K.
    Danielsson, K.
    Fahraeus, R.
    Nylander, K.
    Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-12015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 113, no 2, 321-326 p.Article in journal (Refereed)
    Abstract [en]

    Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged <= 40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

  • 48.
    Sgaramella, Niccola
    et al.
    Univ Naples Federico II, Dept Neurosci Reprod & Dent Sci, Naples, Italy.
    Lindell Jonsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Boldrup, Linda
    Califano, Luigi
    Univ Naples Federico II, Dept Neurosci Reprod & Dent Sci, Naples, Italy.
    Coates, Philip
    Tartaro, Gianpaolo
    Lo Muzio, Lorenzio
    Fåhraeus, Robin
    Colella, Giuseppe
    Dell'Aversana Orabona, Giovanni
    Loljung, Lotta
    Santagata, Mario
    Rosiello, Riccardo
    Wilms, Torben
    Danielsson, Karin
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nylander, Karin
    High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients≤ 40 years but does not correlate with tumour spread2016In: The journal of pathology. Clinical research, ISSN 2056-4538, no 1, 3-8 p.Article in journal (Refereed)
    Abstract [en]

    More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour-free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p = 0.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (< 40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies.

  • 49.
    Söderström, Karin
    et al.
    Umea Univ, Umea Univ Hosp, Dept Radiat Sci, Oncol, Umea, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Zackrisson, Björn
    Umea Univ, Umea Univ Hosp, Dept Radiat Sci, Oncol, Umea, Sweden..
    Jaghagen, Eva Levring
    Umea Univ, Dept Odontol Oral & Maxillofacial Radiol, Umea, Sweden..
    Dysphagia - Results from multivariable predictive modelling on aspiration from a subset of the ARTSCAN trial2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 2, 192-199 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To establish predictive models for late objective aspiration and late patient-reported choking based on dose-volume parameters and baseline patient and treatment characteristics, for patients with head and neck cancer undergoing definitive radiotherapy (RT). The impact of electively treated volume on late aspiration was also investigated. Methods and material: This prospective cohort is a subsample of 124 survivors from the ARTSCAN study. Late aspiration was identified with videofluoroscopy, at a minimum of 25 months after the start of RT. Patient-reported choking was analysed at 12 and 60 months post RT using the EORTC Quality of Life Module for Head and Neck Cancer 35. Univariable and multivariable analyses were performed to describe the association between clinical factors and dose-volume descriptors for organs at risk (OARs) and late dysphagia. Results: Aspiration was found in 47% of the eligible patients. Mean dose to the middle pharyngeal constrictor (MPC), neck dissection post RT and age at randomisation in ARTSCAN were associated to late aspiration. Mean dose to the superior pharyngeal constrictor (SPC) and swallowing complaints at baseline were associated to patient reported choking at both time-points. Conclusions: Three separate risk groups for late aspiration, and two risk groups for late patient-reported choking were identified based on number of risk factors. The size of the electively treated volume could be used as a surrogate for individual OARs predicting late aspiration.

  • 50.
    Ward, Heather A.
    et al.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Wark, Petra A.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Muller, David C.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Steffen, Annika
    German Inst Human Nutr Potsdam Rehbruke, Dept Epidemiol, Nuthetal, Germany..
    Johansson, Mattias
    Int Agcy Res Canc IARC WHO, Lyon, France.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Norat, Teresa
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Gunter, Marc J.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Int Agcy Res Canc IARC WHO, Lyon, France..
    Overvad, Kim
    Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus, Denmark.;Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark..
    Dahm, Christina C.
    Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus, Denmark..
    Halkjaer, Jytte
    Danish Canc Soc Res Ctr Diet Genes & Environm, Copenhagen, Denmark..
    Tojonneland, Anne
    Danish Canc Soc Res Ctr Diet Genes & Environm, Copenhagen, Denmark..
    Boutron-Ruault, Marie-Christine
    Univ Paris Sud, UVSQ, INSERM, Univ Paris Saclay,Generat & Hlth, Villejuif, France.;Gustave Roussy, Villejuif, France..
    Fagherazzi, Guy
    Univ Paris Sud, UVSQ, INSERM, Univ Paris Saclay,Generat & Hlth, Villejuif, France.;Gustave Roussy, Villejuif, France..
    Mesrine, Sylvie
    Univ Paris Sud, UVSQ, INSERM, Univ Paris Saclay,Generat & Hlth, Villejuif, France.;Gustave Roussy, Villejuif, France..
    Brennan, Paul
    Int Agcy Res Canc IARC WHO, Lyon, France..
    Freisling, Heinz
    Int Agcy Res Canc IARC WHO, Lyon, France..
    Li, Kuanrong
    Int Agcy Res Canc IARC WHO, Lyon, France..
    Kaaks, Rudolf
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece.;Acad Athens, Bur Epidemiol Res, Athens, Greece..
    Lagiou, Pagona
    Acad Athens, Bur Epidemiol Res, Athens, Greece.;Univ Athens, Med Sch, Dept Hyg Epidemiol & Med Stat, Athens, Greece.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Panico, Salavatore
    Univ Naples Federico II, Sect Endocrinol, Dept Clin Med & Surg, Naples, Italy..
    Grioni, Sara
    Fdn IRCCS Natl Canc Inst, Epidemiol & Prevent Unit, Milan, Italy..
    Tumino, Rosario
    ASP Ragusa, Civic MP Arezzo Hosp, Canc Registry & Histopathol Unit, Ragusa, Italy..
    Vineis, Paolo
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;HuGeF Fdn, Turin, Italy..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy..
    Peeters, Petra H. M.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands..
    Bueno-de-Mesquita, H. Bas.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands..
    Weiderpass, Elisabete
    UiT Arct Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway.;Inst Population Based Canc Res, Canc Registry Norway, Oslo, Norway.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland..
    Agudo, Antonio
    Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain..
    Ramon Quiros, Jose
    Publ Hlth Directorate, Asturias, Spain.;IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain..
    Larranaga, Nerea
    Publ Hlth Div Gipuzkoa BIODONOSTIA, Basque Reg Hlth Dept, Donostia San Sebastian, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Ardanaz, Eva
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Navarre Publ Hlth Inst, Pamplona, Spain..
    Maria Huerta, Jose
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Sanchez, Maria-Jose
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Univ Cartuja, Res Inst Biosanitary Granada, Andalucian Sch Publ Hlth, Granada, Spain..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Johansson, Ingegerd
    Umea Univ, Dept Odontol, Umea, Sweden..
    Westin, Ulla
    Lund Univ, Dept Otorhinolaryngol, Univ Hosp, Ear Nose & Throat Dept, Malmo, Sweden..
    Wallstrom, Peter
    Lund Univ, Dept Clin Sci, Nutr Epidemiol Res Grp, Skane Univ Hosp, Malmo, Sweden..
    Bradbury, Kathryn E.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Met Sci, MRC Epidemiol Unit, Cambridge, England..
    Khaw, Kay-Tee
    Univ Cambridge, Addenbrookes Hosp, Clin Gerontol Unit, Cambridge, England..
    Pearson, Clare
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Publ Hlth England, Canc Res UK, London, England..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruke, Dept Epidemiol, Nuthetal, Germany..
    Riboli, Elio
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Measured Adiposity in Relation to Head and Neck Cancer Risk in the European Prospective Investigation into Cancer and Nutrition2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 6, 895-904 p.Article in journal (Refereed)
    Abstract [en]

    Background: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer. However, most studies have used self-reported anthropometry which is prone to error. Methods: Among 363,094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of head and neck cancer. Head and neck cancer risk was examined in relation to body mass index (BMI) [lean: <22.5 kg/m(2), normal weight (reference): 22.5-24.9 kg/m(2), overweight 25-29.9 kg/m(2), obese: >= 30 kg/m(2)], waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) using Cox proportional hazards models. Results: Among men, a BMI <22.5 kg/m(2) was associated with higher head and neck cancer risk [HR 1.62; 95% confidence interval (CI), 1.23-2.12)]; BMI was not associated with head and neck cancer among women. WC and WHR were associated with greater risk of head and neck cancer among women (WC per 5 cm: HR, 1.08; 95% CI, 1.02-1.15; WHR per 0.1 unit: HR, 1.64; 95% CI, 1.38-1.93). After stratification by smoking status, the association for WHR was present only among smokers (P-interaction = 0.004). Among men, WC and WHR were associated with head and neck cancer only upon additional adjustment for BMI (WC per 5 cm: HR 1.16; 95% CI, 1.07-1.26; WHR per 0.1 unit: HR, 1.42; 95% CI, 1.21-1.65). Conclusions: Central adiposity, particularly among women, may have a stronger association with head and neck cancer risk than previously estimated.

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