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Ölander, C., Gudjonsson, O., Kinnefors, A., Laurell, G. & Edfeldt, L. (2018). Complications in translabyrinthine surgery of vestibular schwannoma. Acta Oto-Laryngologica, 138(7), 639-645
Open this publication in new window or tab >>Complications in translabyrinthine surgery of vestibular schwannoma
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2018 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, no 7, p. 639-645Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate the risk of complications associated with tumor size and patient's age in translabyrinthine vestibular schwannoma surgery. Methods: 700 patients with vestibular schwannoma primarily underwent translabyrinthine surgery between 1988 and 2014. Pre- and postoperative data were collected in a database and incidence of the postoperative complications cerebrospinal fluid leakage, meningitis, intracranial hemorrhage (ICH), facial nerve function and mortality were assessed and related to the tumor size and patient's age and retrospectively evaluated. Results: The tumor size significantly influenced the incidence of ICH and facial nerve dysfunction whereas age was correlated to facial nerve outcome. Conclusions: The translabyrinthine approach is a safe surgical procedure with relatively low risks of complications. The tumor size was significantly associated with a higher risk of ICH and facial nerve dysfunction whereas age only influenced the facial nerve outcome.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Translabyrinthine surgery, complications, tumor size, age
National Category
Neurology Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-356818 (URN)10.1080/00016489.2018.1427887 (DOI)000432629200008 ()29361875 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Edvardsson Rasmussen, J., Laurell, G., Rask-Andersen, H., Bergquist, J. & Eriksson, P. O. (2018). The proteome of perilymph in patients with vestibular schwannoma: A possibility to identify biomarkers for tumor associated hearing loss?. PLoS ONE, 13(6), Article ID e0198442.
Open this publication in new window or tab >>The proteome of perilymph in patients with vestibular schwannoma: A possibility to identify biomarkers for tumor associated hearing loss?
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0198442Article in journal (Refereed) Published
Abstract [en]

Background Due to the surrounding bone, the human inner ear is relatively inaccessible and difficult to reach for cellular and molecular analyses. However, these types of investigations are needed to better understand the etiology, pathophysiology and progression of several inner ear disorders. Moreover, the fluid from the inner ear cannot be sampled for micro-chemical analyses from healthy individuals in vivo. Therefore, in the present paper, we studied patients with vestibular schwannoma (VS) undergoing trans-labyrinthine surgery (TLS). Our primary aim was to identify perilymph proteins in patients with VS on an individual level. Our second aim was to investigate the proteins identified at a functional level and our final aim was to search for biological markers for tumor-associated hearing loss and tumor diameter. Methods and findings Sixteen patients underwent TLS for sporadic VS. Perilymph was aspirated through the round window before opening the labyrinth. One sample was contaminated and excluded resulting in 15 usable samples. Perilymph samples were analyzed with an online tandem LTQ-Orbitrap mass spectrometer. Data were analyzed with MaxQuant software to identify the total number of proteins and to quantify proteins in individual samples. Protein function was analyzed using the PANTHER Overrepresentation tool. Associations between perilymph protein content, clinical parameters, tumor-associated hearing loss and tumor diameter were assessed using Random Forest and Boruta. In total, 314 proteins were identified; 60 in all 15 patients and 130 proteins only once in 15 patients. Ninety-one proteins were detected in at least 12 out of 15 patients. Random Forest followed by Boruta analysis confirmed that alpha-2-HS-glycoprotein (P02765) was an independent variable for tumor-associated hearing loss. In addition, functional analysis showed that numerous processes were significantly increased in the perilymph. The top three enriched biological processes were: 1) secondary metabolic processes; 2) complement activation and 3) cell recognition. Conclusions The proteome of perilymph in patients with vestibular schwannoma has an inter-individual stable section. However, even in a cohort with homogenous disease, the variation between individuals represented the majority of the detected proteins. Alpha-2-HS-glycoprotein, P02765, was shown to be an independent variable for tumor-associated hearing loss, a finding that needs to be verified in other studies. In pathway analysis perilymph had highly enriched functions, particularly in terms of increased immune and metabolic processes.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-358705 (URN)10.1371/journal.pone.0198442 (DOI)000433900800126 ()29856847 (PubMedID)
Funder
Swedish Research Council, 2015-4870
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved
Counter, S. A., Buchanan, L. H., Ortega, F., Jacobs, A. B. & Laurell, G. (2017). Assessment of the Brainstem- Mediated Stapedius Muscle Reflex in Andean Children Living at High Altitudes. High Altitude Medicine & Biology, 18(1), 37-45
Open this publication in new window or tab >>Assessment of the Brainstem- Mediated Stapedius Muscle Reflex in Andean Children Living at High Altitudes
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2017 (English)In: High Altitude Medicine & Biology, ISSN 1527-0297, E-ISSN 1557-8682, Vol. 18, no 1, p. 37-45Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2017
Keywords
altitude, Andean, auditory, brainstem, children, hearing, hypoxia, stapedius reflex
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-320300 (URN)10.1089/ham.2016.0082 (DOI)000397571000005 ()27860516 (PubMedID)
Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2017-04-18Bibliographically approved
Stenhammar, C., Isaksson, J., Granström, B., Laurell, G. & Tiblom Ehrsson, Y. (2017). Changes in intimate relationships following treatment for head and neck cancer: A qualitative study. Journal of psychosocial oncology, 35(5), 614-630
Open this publication in new window or tab >>Changes in intimate relationships following treatment for head and neck cancer: A qualitative study
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2017 (English)In: Journal of psychosocial oncology, ISSN 0734-7332, E-ISSN 1540-7586, Vol. 35, no 5, p. 614-630Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to determine how patients with head and neck cancer experience changes within their intimate relationships at the end of treatment and detect detrimental and facilitating factors in the process of resuming intimate relationships. Interviews were conducted with 131 patients. A core category - being open versus not sharing the cancer journey - emerged from the patients' narratives and was based on the experiences of engagement/disengagement, openness/fear, and patronizing attitudes/sharing the burden. The findings point to the necessity of patients being open about the disease trajectory and might be understood in the light of theories about potential changes in identity and self-concept.

Keywords
Head and neck cancer, intimate relationships, patients experience, social support, qualitative study
National Category
Cancer and Oncology Psychology
Identifiers
urn:nbn:se:uu:diva-340981 (URN)10.1080/07347332.2017.1339224 (DOI)000413909300007 ()28605311 (PubMedID)
Available from: 2018-02-05 Created: 2018-02-05 Last updated: 2018-02-05Bibliographically approved
Pierre, P. V., Haglöf, J., Linder, B., Engskog, M. K., Arvidsson, T., Pettersson, C., . . . Laurell, G. (2017). Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity. Acta Oto-Laryngologica, 137(10), 1024-1030
Open this publication in new window or tab >>Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity
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2017 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 10, p. 1024-1030Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo.

AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.

MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS.

RESULTS: Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.

Keywords
ABR, cisplatin, hair cell, metabolite profiling, ototoxicity, sodium thiosulfate
National Category
Basic Medicine Analytical Chemistry Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-328151 (URN)10.1080/00016489.2017.1325006 (DOI)000407072000002 ()28537102 (PubMedID)
Funder
AFA Insurance
Available from: 2017-08-18 Created: 2017-08-18 Last updated: 2018-09-07Bibliographically approved
Söderström, K., Nilsson, P., Laurell, G., Zackrisson, B. & Jaghagen, E. L. (2017). Dysphagia - Results from multivariable predictive modelling on aspiration from a subset of the ARTSCAN trial. Radiotherapy and Oncology, 122(2), 192-199
Open this publication in new window or tab >>Dysphagia - Results from multivariable predictive modelling on aspiration from a subset of the ARTSCAN trial
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2017 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 2, p. 192-199Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2017
Keywords
Head and neck cancer, Radiotherapy, Dysphagia, Normal tissue complication probability
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-320781 (URN)10.1016/j.radonc.2016.09.001 (DOI)000395607300004 ()27687824 (PubMedID)
Funder
Swedish Cancer SocietyCancer and Allergy Foundation
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2017-04-25Bibliographically approved
Assadian, F., Kamel, W., Laurell, G., Svensson, C., Punga, T. & Akusjärvi, G. (2017). Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes. PLoS ONE, 12(5), Article ID e0177275.
Open this publication in new window or tab >>Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177275Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-326234 (URN)10.1371/journal.pone.0177275 (DOI)000402062800013 ()28542273 (PubMedID)
Funder
Swedish Cancer Society, 120678, 130469
Available from: 2017-07-06 Created: 2017-07-06 Last updated: 2017-11-29Bibliographically approved
Boldrup, L., Gu, X., Coates, P. J., Norberg-Spaak, L., Fahraeus, R., Laurell, G., . . . Nylander, K. (2017). Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma. OncoTarget, 8(12), 19389-19402
Open this publication in new window or tab >>Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 12, p. 19389-19402Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2017
Keywords
tongue cancer, RNA expression, field cancerization
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-319866 (URN)10.18632/oncotarget.14288 (DOI)000396879200062 ()
Funder
Swedish Cancer Society, 15 06 37
Available from: 2017-04-13 Created: 2017-04-13 Last updated: 2017-11-29Bibliographically approved
Fransson, A. E., Kisiel, M., Pirttilä, K., Pettersson, C., Videhult Pierre, P. & Laurell, G. (2017). Hydrogen Inhalation Protects against Ototoxicity Induced by Intravenous Cisplatin in the Guinea Pig. Frontiers in Cellular Neuroscience, 11, Article ID 280.
Open this publication in new window or tab >>Hydrogen Inhalation Protects against Ototoxicity Induced by Intravenous Cisplatin in the Guinea Pig
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2017 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 11, article id 280Article in journal (Refereed) Published
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.

Keywords
ABR, inner hair cells, outer hair cells, synaptophysin, organic cation transporter 2, copper transporter 1, perilymph metabolomics, in vivo
National Category
Otorhinolaryngology Analytical Chemistry Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-330897 (URN)10.3389/fncel.2017.00280 (DOI)000410583900001 ()28955207 (PubMedID)
Available from: 2017-10-06 Created: 2017-10-06 Last updated: 2018-01-13Bibliographically approved
Jonsson, E. L., Nylander, K., Hallén, L. & Laurell, G. (2017). Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N0. Acta Oto-Laryngologica, 137(8), 877-882
Open this publication in new window or tab >>Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N0
2017 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 8, p. 877-882Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Epidermal growth factor receptor expression, immunoscoring, oral tongue squamous cell carcinoma, prognostic factors, biomarkers
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-316243 (URN)10.1080/00016489.2017.1292049 (DOI)000404684100016 ()28355940 (PubMedID)
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2017-10-19Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-7760-246x

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