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  • 1. Ahlberg, Alexander
    et al.
    al-Abany, Massoud
    Alevronta, Eleftheria
    Friesland, Signe
    Hellborg, Henrik
    Mavroidis, Panayiotis
    Lind, Bengt K
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Esophageal stricture after radiotherapy in patients with head and neck cancer: experience of a single institution over 2 treatment periods2010Ingår i: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 32, nr 4, s. 452-461Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of >45 Gy to the upper esophagus. Treatment of the stricture with Savary-Gilliard bougienage or through scope balloon dilatation is safe and successful but often has to be repeated.

  • 2. Ahlberg, Alexander
    et al.
    Engström, Therese
    Nikolaidis, Polymnia
    Gunnarsson, Karin
    Johansson, Hemming
    Sharp, Lena
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Early self-care rehabilitation of head and neck cancer patients2011Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 131, nr 5, s. 552-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONCLUSIONS: No positive effects of early preventive rehabilitation could be identified. The results do not contradict the proposition that rehabilitation based on self-care can be effective but it is important to establish evidence-based training programs and identify proper instruments for selection of patients and evaluation of intervention.

    OBJECTIVES: Patients with head and neck cancer suffer from functional impairments due to intense treatment. In this study, we investigated the effectiveness of an experimental early preventive rehabilitation using hard, objective end points in a nonselective, longitudinal, prospective cohort study.

    METHODS: In all, 190 patients were included in the program and received instructions for training before the start of treatment with the aim of reducing swallowing problems and reducing mouth opening and stiffness in the neck. A control group of 184 patients was recruited.

    RESULTS: There was no difference in weight loss and 2-year survival between the two groups. No positive effects concerning functional impairments were found in patient-reported outcome measures.

  • 3. Ahlberg, Alexander
    et al.
    Nikolaidis, Polymnia
    Engström, Therese
    Gunnarsson, Karin
    Johansson, Hemming
    Sharp, Lena
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Morbidity of supraomohyoidal and modified radical neck dissection combined with radiotherapy for head and neck cancer: a prospective longitudinal study2012Ingår i: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 34, nr 1, s. 66-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The purpose of this study was to show the investigated impact of supraomohyoidal neck dissection and modified radical neck dissection, both combined with radiotherapy, on cervical range of motion (CROM), mouth opening, swallowing, lymphedema, and shoulder function.

    METHODS: One hundred eight patients who had neck dissections and 98 patients who had non-neck dissections were evaluated in a prospective, nonselective, longitudinal cohort study by a physiotherapist and a speech-language pathologist (SLP) before the start of radiotherapy and up to 12 months after treatment.

    RESULTS: The incidence of shoulder disability after neck dissection was 18%. Supraomohyoidal neck dissection had no significant effect on the evaluated parameters at any time point. Modified radical neck dissection significantly reduced CROM and mouth opening 2 months after treatment, but after 12 months only cervical rotation was still significantly reduced.

    CONCLUSION: In patients treated with external beam radiation (EBRT), modified radical neck dissection induced additional morbidity regarding CROM but not regarding mouth opening, swallowing, and lymphedema 1 year after treatment. Both modified radical neck dissection and supraomohyoidal neck dissection induced shoulder disability.

  • 4.
    Alevronta, Eleftheria
    et al.
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden.
    Ahlberg, Alexander
    Department of Otolaryngology, Karolinska University Hospital, Stockholm, Sweden.
    Mavroidis, Panayiotis
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden.
    al-Abany, Massoud
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Friesland, Signe
    Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
    Tilikidis, Aris
    Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Lind, Bengt K
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden.
    Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy2010Ingår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 97, nr 1, s. 54-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck.

    MATERIAL AND METHODS: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model.

    RESULTS: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D(50)=61.5 Gy (52.9-84.9 Gy), γ=1.4 (0.8-2.6) and s=0.1 (0.01-0.3).

    CONCLUSIONS: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.

  • 5. Berglin, Cecilia Engmer
    et al.
    Pierre, Pernilla Videhult
    Bramer, Tobias
    Edsman, Katarina
    Ehrsson, Hans
    Eksborg, Staffan
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model2011Ingår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 68, nr 6, s. 1547-1556Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model. The release of thiosulfate (0.1 M) from HYA gel (0.5% w/w) was explored in vitro. Thiosulfate in the scala tympani perilymph of the cochlea 1 and 3 h after application of thiosulfate in HYA gel to the middle ear was quantified with HPLC and fluorescence detection. Thiosulfate in blood and CSF was also explored. The potential otoprotective effect was evaluated by hair cell count after treatment with thiosulfate in HYA gel applied to the middle ear 3 h prior to cisplatin injection (8 mg/kg b.w.). HYA did not impede the release of thiosulfate. Middle ear administration of thiosulfate in HYA gel gave high concentrations in the scala tympani perilymph while maintaining low levels in blood, and it protected against cisplatin-induced hair cell loss. HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary.

  • 6.
    Boldrup, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Differences in p63 expression in SCCHN tumours of different sub-sites within the oral cavity2011Ingår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 47, nr 9, s. 861-865Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Squamous cell carcinoma of the head and neck, SCCHN, the sixth most common cancer in the world, comprises tumours of differentanatomical sites. The overall survival is low, and there are no good prognostic or predictive markers available. The p53 homologue, p63, plays an important role in development of epithelial structures and has also been suggested to be involved in development of SCCHN. However, most studies on p63 in SCCHN have not taken into account the fact that this group of tumours is heterogeneous in terms of the particular site of origin of the cancer. Mapping and comparing p63 expression levels in tumours and corresponding clinically normal tissue in SCCHN from gingiva, tongue and tongue/floor of the mouth revealed clear differences between these regions. In normal samples from tongue and gingiva, tongue samples showed 2.5-fold higher median p63 expression and also more widespread expression compared to gingival samples. These results emphasise the importance of taking sub-site within the oral cavity into consideration in analyses of SCCHN.

  • 7.
    Boldrup, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    p63 transcriptionally regulates BNC1, a Pol I and Pol II transcription factor that regulates ribosomal biogenesis and epithelial differentiation2012Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, nr 9, s. 1401-1406Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The p53-family member, p63 is a transcription factor that influences cellular adhesion, motility, proliferation, survival and apoptosis, and has a major role in regulating epithelial stem cells. Expression of p63 is often dysregulated in squamous cell carcinomas of the head and neck. In this study we show that p63 induces the expression of the basal epithelial transcription factor, Basonuclin 1. Basonuclin 1 is an unusual transcription factor that interacts with a subset of promoters of genes that are transcribed by both RNA polymerase-I and -II and has roles in maintaining ribosomal biogenesis and the proliferative potential of immature epithelial cells. Chromatin immunoprecipitation and reporter assays demonstrate that Basonuclin 1 is a direct transcriptional target of p63 and we also show that up-regulation of Basonuclin 1 is a common event in squamous cell carcinomas of the head and neck. These data identify a new transcriptional programme mediated by p63 regulation of the Basonuclin 1 transcription factor in squamous cell carcinomas and provide a novel link of p63 with the regulation of ribosomal biogenesis in epithelial cancer.

  • 8.
    Boldrup, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J
    Tayside Tissue Bank Division of Medical Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
    Wahlgren, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Subsite-based alterations in miR-21, miR-125b, and miR-203 in squamous cell carcinoma of the oral cavity and correlation to important target proteins.2012Ingår i: Journal of Carcinogenesis, ISSN 0974-6773, E-ISSN 1477-3163, Vol. 11, s. 18-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNA molecules with an essential role in regulation of gene expression. miRNA expression profiles differ between tumor and normal control tissue in many types of cancers and miRNA profiling is seen as a promising field for finding new diagnostic and prognostic tools.

    MATERIALS AND METHODS: In this study, we have analyzed expression of three miRNAs, miR-21, miR-125b, and miR-203, and their potential target proteins p53 and p63, known to be deregulated in squamous cell carcinoma of the head and neck (SCCHN), in two distinct and one mixed subsite in squamous cell carcinoma in the oral cavity.

    RESULTS: We demonstrate that levels of miRNA differ between tumors of different subsites with tongue tumors showing significant deregulation of all three miRNAs, whereas gingival tumors only showed significant downregulation of miR-125b and the mixed group of tumors in tongue/floor of the mouth showed significant deregulation of miR-21 and miR-125b. In the whole group of oral squamous cell carcinoma (SCC), a significant negative correlation was seen between miR-125b and p53 as well as a significant correlation between TP53 mutation status and miR-125b.

    CONCLUSION: The present data once again emphasize the need to take subsite into consideration when analyzing oral SCC and clearly show that data from in vitro studies cannot be transferred directly to the in vivo situation.

  • 9.
    Boldrup, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Gu, Xiaolian
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J.
    Norberg-Spaak, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Fåhraeus, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic; Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, 75010 Paris, France.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Surgical Sciences/ENT, Uppsala University, 752 36 Uppsala, Sweden.
    Wilms, Torben
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma2017Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 12, s. 19389-19402Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Duan, Maoli
    et al.
    Center for Hearing and Communication Research, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Bjelke, Börje
    Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Fridberger, Anders
    Center for Hearing and Communication Research, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Counter, S Allen
    Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Klason, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Skjönsberg, Åsa
    Center for Hearing and Communication Research, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Herrlin, Petra
    Center for Hearing and Communication Research, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Borg, Erik
    Ahlsen Research Institute, Örebro University Hospital, 701 85 Örebro, Sweden.
    Laurell, Göran
    Center for Hearing and Communication Research, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Imaging of the guinea pig cochlea following round window gadolinium application2004Ingår i: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 15, nr 12, s. 1927-1930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Precise, non-invasive determination of the aetiology and site of pathology of inner ear disorders is difficult. The aim of this study was to describe an alternative method for inner ear visualization, based on local application of the paramagnetic contrast agent gadolinium. Using a 4.7 T MRI scanner, high contrast images of all four cochlear turns were obtained 3.5 h after placing gadolinium on the round window membrane. Gadolinium cleared from the cochlea within 96 h. Auditory brainstem response measurements performed on a separate group of animals showed no significant threshold shifts after the application, indicating that gadolinium is non-toxic to the guinea pig cochlea.

  • 11. Duan, Maoli
    et al.
    Chen, Zhiqiang
    Qiu, Jianxin
    Ulfendahl, Mats
    Laurell, Göran
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Borg, Erik
    Ruan, Runsheng
    Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat2006Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Acta Otolaryngol, Vol. 126, nr 11, s. 1140-7Artikel i tidskrift (Refereegranskat)
  • 12. Duan, Maoli
    et al.
    Laurell, Göran
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Qiu, Jianxin
    Borg, Erik
    Susceptibility to impulse noise trauma in different species: guinea pig, rat and mouse.2007Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, nr 3, s. 277-283Artikel i tidskrift (Refereegranskat)
  • 13.
    Ehrsson, Ylva Tiblom
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
    Hellström, Per M
    Department of Medical Science, Uppsala University Hospital, 751 85 Uppsala, Sweden.
    Brismar, Kerstin
    Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden.
    Sharp, Lena
    Department of Oncology, Karolinska University Hospital, 118 83 Stockholm, Sweden.
    Langius-Eklöf, Ann
    School of Medical and Health Sciences, Örebro University, 701 82 Örebro, Sweden.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Explorative study on the predictive value of systematic inflammatory and metabolic markers on weight loss in head and neck cancer patients undergoing radiotherapy2010Ingår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 18, nr 11, s. 1385-1391Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: This study aimed to explore the predictive value of systematic inflammatory and metabolic markers in head and neck (H&N) cancer patients during radiotherapy (RT).

    METHODS: Twenty-seven patients were evaluated. The protocol included serial blood tests [highly sensitive C-reactive protein (hsCRP), albumin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1) and ghrelin], measurements of body weight and assessment of oral mucositis.

    RESULTS: The mean nadir of weight loss was observed at the end of RT. At the time of diagnosis, mean hsCRP was 5.2 ± 1.0 mg/L. HsCRP significantly increased during RT and decreased during the post-RT period. Mean maximum hsCRP was 35.8 ± 8.5 mg/L, with seven patients reaching >40 mg/L. A numerical decrease of albumin (by 18.2%) and only small changes in IGF-1, IGFBP-1 and ghrelin levels were observed. None of the metabolic parameters was significantly associated with weight loss.

    CONCLUSIONS: HsCRP increased in response to RT for H&N cancer as a sign of irradiation-induced inflammation. Weight loss was not preceded by changes of the metabolic parameters, indicating that assessment of the blood markers used in this study is of little value. Regular body weight measurement and assessment of oral mucositis are feasible, cheap and important procedures to control the metabolic homeostasis during RT.

  • 14. Ehrsson, Ylva Tiblom
    et al.
    Langius-Eklöf, Ann
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nutritional surveillance and weight loss in head and neck cancer patients2012Ingår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 20, nr 4, s. 757-765Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This retrospective single-institution cohort study aims to evaluate if therapeutic approach, tumour site, tumour stage, BMI, gender, age and civil status predict body weight loss and to establish the association between weight loss on postoperative infections and mortality. Consecutive patients with head and neck cancer were seen for nutritional control at a nurse-led outpatient clinic and followed-up for 2 years after radiotherapy. Demographic, disease-specific and nutrition data were collected from case records. The primary outcome measure was maximum body weight loss during the whole study period. The nadir of body weight loss was observed 6 months after radiotherapy. In total, 92 patients of 157 (59%) with no evidence of residual tumour after treatment received enteral nutrition. The mean maximum weight loss for patients receiving enteral nutrition and per oral feeding was 13% and 6%, respectively (p < 0.001). Using multivariate analysis, tumour stage (p < 0.001) was the only independent factor of maximum weight loss. Weight loss was not significantly related to risk for postoperative infection. Weight loss is frequently noted among head and neck cancer patients during and after treatment. Weight loss was not found to be associated with postoperative infections and mortality. Nutritional surveillance is important in all patients, but special attention should be given to those on enteral nutrition and those with more advanced disease.

  • 15.
    Ekborn, Andreas
    et al.
    Departments of Otolaryngology—Head and Neck Surgery, Stockholm, Sweden.
    Hansson, Johan
    Oncology-Radiology, Stockholm, Sweden.
    Ehrsson, Hans
    Oncology-Pathology, Stockholm, Sweden.
    Eksborg, Staffan
    Woman and Child Health, Stockholm, Sweden.
    Wallin, Inger
    Karolinska Institute, and Karolinska Pharmacy, Stockholm, Sweden.
    Wagenius, Gunnar
    Department of Oncology, Uppsala University Hospital (Akademiska Sjukhuset), Uppsala, Sweden.
    Laurell, Göran
    Departments of Otolaryngology—Head and Neck Surgery, Stockholm, Sweden.
    High-dose cisplatin with amifostine: ototoxicity and pharmacokinetics2004Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 114, nr 9, s. 1660-1667Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES/HYPOTHESIS: Ototoxicity is a common side effect of high-dose cisplatin treatment. Thiol-containing chemoprotectors ameliorate cisplatin ototoxicity under experimental conditions. The trial was initiated to test the efficacy of amifostine protection in high-dose cisplatin treatment (125-150 mg/m) for metastatic malignant melanoma, to correlate the ototoxic outcome with cisplatin pharmacokinetics, and to evaluate the importance of using a selective analytical method for the quantification of cisplatin.

    STUDY DESIGN: Prospective study of 15 patients with stage IV malignant melanoma.

    METHODS: Clinical follow-up of therapeutic response, pure-tone audiometry, and analysis of cisplatin and its monohydrated complex in blood ultrafiltrate by liquid chromatography with postcolumn derivatization were performed. Ultrafiltered blood platinum was analyzed by inductively coupled plasma mass spectrometry.

    RESULTS: Ototoxicity and gastrointestinal toxicity were the most prominent side effects. Three patients ultimately required hearing aids. All patients had audiometric changes at one or more frequencies after the second treatment course, and all but one patient reported auditory symptoms. No correlation was found between hearing loss and blood cisplatin pharmacokinetics. Platinum levels determined by inductively coupled plasma mass spectrometry were higher than total platinum levels calculated from cisplatin and monohydrated complex concentrations obtained by liquid chromatography analysis.

    CONCLUSION: Ototoxicity was unacceptable despite amifostine treatment. Cisplatin pharmacokinetics during the first treatment course were not predictive of hearing loss. Amifostine caused a lowering of dose-normalized area under the concentration-time curve for cisplatin and monohydrated complex. Use of the unselective inductively coupled plasma mass spectrometry analysis leads to an overestimation of active drug. Selective analysis of cisplatin is especially important when evaluating cisplatin pharmacokinetics during chemoprotector treatment.

  • 16. Engmér, Cecilia
    et al.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Bagger-Sjöbäck, Dan
    Rask-Andersen, Helge
    Immunodefense of the round window2008Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 118, nr 6, s. 1057-1062Artikel i tidskrift (Refereegranskat)
    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.

  • 17. Hellberg, Victoria
    et al.
    Wallin, Inger
    Eriksson, Sofi
    Hernlund, Emma
    Jerremalm, Elin
    Berndtsson, Maria
    Eksborg, Staffan
    Arnér, Elias SJ
    Shoshan, Maria
    Ehrsson, Hans
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Cisplatin and oxaliplatin toxicity: importance of cochlear kinetics as a determinant for ototoxicity2009Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 101, nr 1, s. 37-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.

    METHODS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration-time curve (AUC). Statistical tests were two-sided.

    RESULTS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 microM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 microg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 microM x minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.

    CONCLUSION: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.

  • 18.
    Holm, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Eriksson, Irene
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Laurell, Göran
    Department of Surgical Sciences, Division of Otorhinolaryngology, Uppsala University.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olofsson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papillomaManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objectives: Sinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology.

    Aims: The aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort.

    Material and Methods: Subjects were identified from our regional center cohort of 88 SIP patients treated between 1984-2014. From these subjects, 54 were included in this study.  Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP.  Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test.

    Results: HPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11.  Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples.

    Conclusion: Since only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.

  • 19.
    Isaksson, Joakim
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete.
    Salander, Pär
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete.
    Granström, Brith
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Uppsala universitet, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Critical incidents reveal how patients with head and neck cancer construct their 'secure base' as a 'helping system'2014Ingår i: Journal of psychosocial oncology, ISSN 0734-7332, E-ISSN 1540-7586, Vol. 32, nr 3, s. 322-341Artikel i tidskrift (Refereegranskat)
    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. The present 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 it 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, i.e. how the found factors of a helping system can be operationalized in clinical practice.

  • 20.
    Jonsson, Eva Lindell
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallen, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Effect of radiotherapy on expression of hyaluronan and EGFR and presence of mast cells in squamous cell carcinoma of the head and neck2012Ingår i: ONCOL LETT, ISSN 1792-1074, Vol. 4, nr 6, s. 1177-1182Artikel i tidskrift (Refereegranskat)
    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.

  • 21. Kreimer, Aimée R
    et al.
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    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 cancer2013Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, nr 21, s. 2708-2715Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    Laurell, Göran
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Ekborn, Andreas
    Viberg, Agneta
    Canlon, Barbara
    Effects of a single high dose of cisplatin on the melanocytes of the stria vascularis in the guinea pig2007Ingår i: Audiol Neurootol, ISSN 1421-9700, Vol. 12, nr 3, s. 170-178Artikel i tidskrift (Refereegranskat)
  • 23.
    Laurell, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Institut National de la Santé et de la Recherche Médicale, Department of Physiology, Faculté Xavier Bichat, Université Paris, Center for Hearing and Communication.
    Teixeira, Marie
    Duan, Maoli
    Sterkers, Olivier
    Ferrary, Evelyne
    Intact blood-perilymph barrier in the rat after impulse noise trauma2008Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, nr 6, s. 608-612Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONCLUSION: The permeability of the blood-labyrinth barrier for radioactive mannitol was unchanged after impulse noise trauma. The present findings are contradictory to the theory of an increased permeability in the blood-labyrinth barrier as a result of extensive noise exposure.

    OBJECTIVE: Noise trauma is reported to cause multiple effects on the cochlea including mechanical and metabolic damage. The aim of the study was to observe the effects of impulse noise on cochlear homeostasis.

    MATERIALS AND METHODS: A well-established rat model was used for evaluation of the early effects of impulse noise trauma on the integrity of the blood-perilymph barrier. To evaluate whether a blood-perilymph barrier disruption contributes to cochlear injury after impulse noise, the paracellular transport of radioactive mannitol into scala vestibuli perilymph (PLV) and electrolyte concentration in perilymph were estimated. Thirteen animals exposed to synthesized impulses of 160 dB SPL peak value, at a rate of 100 pulses, were designed as the study group and 15 rats not exposed to noise were designed as the control group. After mannitol infusion each ear of the animal in the study group was separately exposed to impulse noise and PLV samples were taken during 2 h post-infusion. In the control group, corresponding PLV samples were taken after mannitol injection.

    RESULTS: At 2 h after mannitol infusion there was no difference in PLV mannitol concentration in the study group and control group (21.5%+/-2.2 and 20.5%+/-2.1, respectively). Impulse noise had no effect on the electrochemical composition of PLV.

  • 24. Lindblom, Ulrika
    et al.
    Nilsson, Per
    Gärskog, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Kjellen, Elisabeth
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Wahlberg, Peter
    Zackrisson, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Levring Jäghagen, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Aspiration as a late complication after accelerated versus conventional radiotherapy in patients with head and neck cancer2016Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, nr 3, s. 304-311Artikel i tidskrift (Refereegranskat)
    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).

  • 25.
    Loizou, Christos
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Arvidsson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olofsson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance2015Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, nr 10, s. 1058-1064Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Loizou, Christos
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Surgical Sciences, Division of Otorhinolaryngology, Uppsala University.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Olofsson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Voice and quality of life in patients with recurrent respiratory papillomatosis in a northern Sweden cohort2014Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, ISSN 1651-2251 (online), Vol. 134, nr 4, s. 401-406Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract 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.

  • 27.
    Loizou, Christos
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Surgical Sciences, Division of Otorhinolaryngology, Uppsala University.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Öfverman, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stefansson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olofsson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus2015Ingår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 10, nr 6, s. 3565-3572Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Loljung, Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J.
    Nekulova, Marta
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Wahlgren, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Wilms, Torben
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Widlöf, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hansel, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue2014Ingår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 43, nr 1, s. 14-19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Backgroundp63 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 (Np63) 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. MethodsTotal p63, Np63 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. ResultsAll 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 2years 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. Np63 was expressed in all tumours, whereas expression of TAp63 was seen only in 59/87 patients, usually at very low levels. ConclusionsBased on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.

  • 29. Lorito, Guiscardo
    et al.
    Hatzopoulos, Stavros
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Campbell, Kathleen C. M.
    Petruccelli, Joseph
    Giordano, Pietro
    Kochanek, Krzysztof
    Sliwa, Lech
    Martini, Alessandro
    Skarzynski, Henryk
    Dose-dependent protection on cisplatin-induced ototoxicity: an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model2011Ingår i: Medical Science Monitor, ISSN 1234-1010, E-ISSN 1643-3750, Vol. 17, nr 8, s. BR179-BR186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Sprague-Dawley rats were used as an acute cisplatin ototoxicity model to compare the chemo-protective efficacy of 2 sulphur-containing antioxidants (D-methionine, N-L-acetylcysteine) and 1 seleno-organic compound (ebselen). Each putative chemo-protective agent was tested at 3 different dosages in order to assess the influence of dose on auditory preservation.

    Material/Methods: A total of 40 Sprague-Dawley albino male rats were used in the study. Animals were divided into 10 groups, 3 groups of different doses for each protective agent and a cisplatin-treated control group. The animals were weight-matched before drug exposure to ensure similar weights in all groups. Auditory function was assessed with auditory brainstem responses and distortion product otoacoustic emissions at time zero and at 96 hours post-treatment.

    Results: At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups. All ebselen-treated animals presented significant threshold elevations. At 12 and 16 kHz, only the groups treated with 300, 450 mg/kg of D-Met and 475 mg/kg of NAC presented thresholds comparable to the pre-treatment ABR data. The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations. The DPOAE data analysis showed that only the animals from the 350 mg/kg D-met group presented lack of statistical differences between the pre and post recordings.

    Conclusions: Considering the outcome from the ABR and DPOAE analyses together, only the 350 mg/kg D-met group presented a complete auditory preservation against the 14 mg/kg cisplatin administered i.v. Data from ebselen pre-treated Sprague-Dawley albino male rats demonstrate that ebselen dosages up to 12 mg/kg given by i.p. administration lack auditory preservation in this species.

  • 30.
    Lundqvist, Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The importance of stromal inflammation in squamous cell carcinoma of the tongue2012Ingår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, nr 5, s. 379-383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Histological risk assessment evaluating worst pattern of tumour invasion (WPOI), and lymphocytic response (LR), has previously been shown to be of prognostic significance in squamous cell carcinomas of the head and neck (SCCHN). SCCHN is a heterogeneous group of tumours including tumours located in the oral cavity, of which the majority is located in the tongue.

    Methods: Haematoxylin/eosin-stained slides from diagnostic biopsies from 94 cases of SCC on the tongue were evaluated for WPOI and LR. Within the inflammatory infiltrate, the percentage of eosinophilic granulocytes was also estimated. Results were correlated with clinical data such as response to treatment and recurrence.

    Results: For WPOI the majority of patients, 84%, showed small invasive tumours islands with a size <15 cells (grade 4). No correlation with survival, response to treatment or recurrence was seen for WPOI. More than half of the patients showed a dense lymphocytic infiltrate, a factor that was significantly correlated with complete response to radio therapy. Of the patients with dense lymphoid infiltrate, the majority, 63%, did not either have a recurrence. No significant correlation with recurrence, response to treatment or any other factor was seen for presence of eosinophils.

    Conclusions:  Data clearly showed that tongue tumours have a split invasive growth pattern and an intense inflammatory response at the tumour interface. Results also indicated that evaluation of the intensity of the inflammatory infiltrate at the tumour interface in tongue SCC could provide information of potential importance for choice of treatment and prognosis.

  • 31.
    Mavroidis, Panayiotis
    et al.
    Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden .
    Lind, Bengt K
    Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden .
    Theodorou, Kyriaki
    Department of Medical Physics, Larissa University Hospital, Larissa, Greece .
    Laurell, Göran
    Department of Otolaryngology, Head and Neck Surgery, Karolinska Hospital, Stockholm, Sweden .
    Fernberg, Jan-Olof
    Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden .
    Lefkopoulos, Dimitrios
    Department of Radiation Physics, Tenon Hospital, Paris, France .
    Kappas, Constantin
    Department of Medical Physics, Larissa University Hospital, Larissa, Greece .
    Brahme, Anders
    Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden .
    Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy2004Ingår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 49, nr 16, s. 3797-3816Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

  • 32. Norling, Rikke
    et al.
    Grau, Cai
    Nielsen, Michael B
    Homøe, Preben
    Sørensen, Jens A
    Lambertsen, Karin
    Bundgaard, Troels
    Mäkitie, Antti
    Grénman, Reidar
    Larenne, Jussi
    Koivunen, Petri
    Virtaniemi, Jukka
    Gudjonsson, Arnar
    Jetlund, Olav
    Abendstein, Helmut
    Rikardsen, Oddveig
    Lybak, Stein
    Wennerberg, Johan
    Högmo, Anders
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Westerborn, Anders
    Hammerlid, Eva
    Tytor, Wieslaw
    Cederblad, Lena
    von Buchwald, Christian
    Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas-A questionnaire survey in the Nordic countries2012Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, nr 3, s. 355-361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n = 4), Finland (n = 5), Iceland (n = 1), Norway (n = 4) and Sweden (n = 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN+) or negative (cN0). Results. All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN+, but the cut-off measures vary from 0.8 to 2.0 cm. Conclusion. Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN+ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC.

  • 33.
    Nyqvist, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Otolaryngology and Head and Neck Surgery, Skåne University Hospital, Lund.
    Fransson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Otolaryngology and Head and Neck Surgery, Uppsala University Hospital.
    Hammerlid, Eva
    Kjellén, Elisabeth
    Franzén, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Söderström, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wickart-Johansson, Gun
    Friesland, Signe
    Sjödin, Helena
    Brun, Eva
    Ask, Anders
    Nilsson, Per
    Ekberg, Lars
    Björk-Eriksson, Thomas
    Nyman, Jan
    Lödén, Britta
    Lewin, Freddi
    Reizenstein, Johan
    Lundin, Erik
    Zackrisson, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    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 up2016Ingår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 118, nr 2, s. 335-341Artikel i tidskrift (Refereegranskat)
    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.

  • 34.
    Olofsson, Katarina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Loizou, Christos
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Studie av larynxpapillom i norra Sverige: två fall av onkogena HPV bland 26 patienter2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 21, s. 1187-1189Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Ingen signifikant skillnad mellan könen noterades i denna studie av en grupp patienter i Norrland där man jämfört kvinnor (n = 8, medianålder 46 år) och män (n = 18, me­dianålder 32 år) med larynxpapillom med avseende på aktuell ­ålder, sjukdomsduration, dia­gnosperiod i livet, sjukdomsutveckling, operationstillfällen under sjukdomsperioden, ­papillomlokalisation i luft­vägar och HPV-typ. Brytpunkten för hög respek­tive låg behandlingsfrekvens förlades till medelvärdet 1 behandling/år. Vid jämförelse mellan patienter med hög (≥ 1 behandling/år, n = 11, medianålder 31 år) respektive låg behandlingsfrekvens (< 1 behandling/år, n = 15, medianålder 45 år) ­registrerades signifikant ­högre ålder i gruppen med låg behandlingsfrekvens (P = 0,01).

  • 35.
    Ottosson, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Olsson, Cecilia
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    The experience of food, eating and meals following radiotherapy for head and neck cancer: a qualitative study2013Ingår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 22, nr 7-8, s. 1034-1043Artikel i tidskrift (Refereegranskat)
    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: ‘Along 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.

  • 36.
    Ottosson, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Zackrisson, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kjellén, Elisabeth
    Lunds Universitet, Klinisk vetenskap.
    Nilsson, Per
    Lunds Universitet, Klinisk vetenskap.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Weight loss in patients with head and neck cancer during and after conventional and accelerated radiotherapy2013Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, nr 4, s. 711-718Artikel i tidskrift (Refereegranskat)
    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.

  • 37. Qiu, Jian-xin
    et al.
    Fang, Xian-zhao
    Tong, Bu-shen
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Duan, Mao-li
    [Study of sensitivity to impulse noise in guinea pig, rat and mouse]2004Ingår i: Zhonghua er bi yan hou ke za zhi, ISSN 0412-3948, Vol. 39, nr 8, s. 472-475Artikel i tidskrift (Refereegranskat)
    Abstract [zh]

    OBJECTIVE: To study sensitivity to impulse noise in guinea pig, rat and mice. METHODS: Six groups were divided. Group I: Guinea pigs (n = 5) were exposed to 50 impulses of 160 dB SPL; Group II: Guinea pigs (n = 5) were exposed to 100 impulses of 160 dB SPL; Group III: Guinea pigs (n = 5) were exposed to 200 impulses of 160 dB SPL; Group IV: Guinea pigs (n = 6) were exposed 400 impulses of 160 dB SPL; Group V: Rats (n = 10) were exposed to 50 impulses of 160 dB SPL; Group VI: Mice (n = 10) were exposed to 50 impulses of 160 dB SPL. ABR thresholds were determined prior to, immediately, one day, one week, two weeks and four weeks after impulse noise exposure. RESULTS: The rat and mice were shown temporary threshold shift (TTS) and permanent threshold shift (PTS) after 50 times impulse noise (160), while no TTS and PTS in the guinea pigs but it was shown TTS and PTS after 400 times impulse noise (160). CONCLUSIONS: Sensitivity to impulse noise is different among guinea pig, rat and mouse. Guinea pig has less sensitivity to impulse noise while rat and mouse have higher sensitivity to impulse noise. In addition, rat has higher sensitivity to impulse noise than mouse.

  • 38.
    Rentoft, Matilda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip John
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Transcriptional profiling of formalin fixed paraffin embedded tissue: pitfalls and recommendations for identifying biologically relevant changes2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 4, s. e35276-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Expression profiling techniques have been used to study the biology of many types of cancer but have been limited to some extent by the requirement for collection of fresh tissue. In contrast, formalin fixed paraffin embedded (FFPE) samples are widely available and represent a vast resource of potential material. The techniques used to handle the degraded and modified RNA from these samples are relatively new and all the pitfalls and limitations of this material for whole genome expression profiling are not yet clarified. Here, we analyzed 70 FFPE tongue carcinoma samples and 17 controls using the whole genome DASL array covering nearly 21000 genes. We identified that sample age is related to quality of extracted RNA and that sample quality influences apparent expression levels in a non-random manner related to gene probe sequence, leading to spurious results. However, by removing sub-standard samples and analysing only those 28 cancers and 15 controls that had similar quality we were able to generate a list of 934 genes significantly altered in tongue cancer compared to control samples of tongue. This list contained previously identified changes and was enriched for genes involved in many cancer-related processes such as tissue remodelling, inflammation, differentiation and apoptosis. Four novel genes of potential importance in tongue cancer development and maintenance, SH3BGL2, SLC2A6, SLC16A3 and CXCL10, were independently confirmed, validating our data. Hence, gene expression profiling can be performed usefully on archival material if appropriate quality assurance steps are taken to ensure sample consistency and we present some recommendations for the use of FFPE material based on our findings.

  • 39.
    Rentoft, Matilda
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip John
    Univ Dundee, Ninewells Hosp & Med Sch, Tayside Tissue Bank, Med Res Inst, Dundee DD1 9SY, Scotland.
    Loljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wilms, Torben
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Univ Uppsala Hosp, Dept Surg Sci ENT, S-75185 Uppsala, Sweden.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue2014Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 35, nr 5, s. 4191-4198Artikel i tidskrift (Refereegranskat)
    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.

  • 40.
    Rentoft, Matilda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Fahlén, Jessica
    Umeå universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Coates, PJ
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Sjöström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Rydén, Patrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    miRNA analysis of formalin-fixed squamous cell carcinomas of the tongue is affected by age of the samples2011Ingår i: International Journal of Oncology, ISSN 1019-6439, Vol. 38, nr 1, s. 61-69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Global miRNA expression arrays were used for analysis of 836 miRNAs in formalin-fixed paraffin-embedded samples from 21 tongue cancer patients and 8 controls. Samples had been stored for one to eleven years. Results separated tumour samples from controls, however, the largest variation was correlated to sample storage time, detectable already after one year. With the use of a linear regression model we could adjust for the storage-dependent effect, leading to the identification of 54 differentially expressed miRNAs in tongue cancer, compared to 16 when using standard normalization, including up-regulation of a novel miRNA, miR-424.

  • 41.
    Rentoft, Matilda
    et al.