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Background: The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors' HRQOL was also compared to reference scores from the population.

Methods: In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated.

Results: HRQOL was associated with gender, with males scoring better than females on a few scales. Patients' HRQOL was more associated with treatment than tumor stage. Patients' HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss.

Conclusions: The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.

The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.

Background: Peritonsillar abscess (PTA) can be treated with aspiration or incision for drainage, but a subsequent PTA can occur if tonsillectomy is not performed. Better understanding is needed of when tonsillectomy should be performed to avoid PTA recurrence.

Objective: This study investigated the recurrence rate of PTA following aspiration or incision for drainage and evaluated the risk factors for recurrence.

Methods: The medical records of 292 patients treated for PTA were reviewed. Recurrence of PTA and elective or quinsy tonsillectomy were the primary endpoints. A Cox proportional hazards regression model for PTA recurrence was constructed with sex, age, and PTA history as predictors.

Results: Young age was the only significant predictor of PTA recurrence. Patients aged 15 to 24 years had a 30-day recurrence rate of 15.5% and a total recurrence rate of 26.6%. The total recurrence rate among patients over 30 years of age was significantly less at 4.0% (Fisher’s exact test, p <.05).

Conclusion and Significance: Based on our results, tonsillectomy should be considered for PTA in patients between 15 and– 25 years of age and, to effectively avoid future recurrence of PTA, should be performed urgently.

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.

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.

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.

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.

Transporter associated with antigen processing 1 (TAP1) and TAP2 serve pivotal roles in adaptive immunity. Tumor cells often show reduced antigen presentation on their surface as one mechanism to escape immune recognition. Whether downregulation of TAPs is a common mechanism of tumor immune evasion in squamous cell carcinoma of the oral tongue (SCCOT) is unclear. In the present study, samples from 78 patients with SCCOT and 17 patients with benign hyperplastic tongue lesions were analyzed for TAP1 and TAP2 expression by immunohistochemistry. The percentage of positive cells and staining intensity were scored. Associations with clinicopathological variables and survival outcome were also investigated. The results demonstrated that TAP1 and TAP2 levels were highly associated with each other in individual samples and were upregulated in SCCOT compared with benign lesions (P<0.001). The proportion of TAP1‐ or TAP2‐positive tumor cells was >80% in all but two of the tumors, whereas 25.6 and 23.0% of the tumors showed weak intensity of TAP1 and TAP2, respectively. There were no significant associations with clinicopathological variables or survival outcomes between TAP‐intermediate/strong and TAP‐weak tumors. However, in patients <70 years old and with early stage SCCOT, male patients had better outcomes than female patients (log‐rank P<0.05), and the best outcome was observed in male patients with intermediate/strong TAP expression. In conclusion, loss of TAP was not a frequent event in SCCOT and stronger TAP expression in male patients was associated with improved survival, providing further evidence for sex‐specific immune modulation in cancer.

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

Background: This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT).

Methods: CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients.

Results: The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems.

Conclusion: One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients.

The embryonic mouse inner ear was used as a model with which to study ototoxicity and tissue interactions. The inner ear anlage can be explanted and cultured in vitro from about the 12th gestational day (gd), and will differentiate parallel with the inner ear developing in vivo until a time corresponding to birth (21st gd). During this period the ovoid sac develops into the labyrinth.

In the present thesis work, otic anlagen from gd 12, 13, 13.5, 15 and 16 were used. As a rule the explants were kept in culture until a time point equivalent to the 21st gd.

Analyses using freeze-fracture technique and transmission electron microscopy showed that in cultured 13th gd otocysts the development of junctional complexes followed the same principal pattern as in vivo. Tight junctions develop into many strands lying parallel to the apical surface of all epithelial cells. Uncoupling of the hair cells occurs with loss of gap junctions. Some tight junctions had an aberrant appearence, with in part very thick strands and strands running at right angles to the apical surface.

All aminoglycosides are potentially ototoxic. In the inner ear, outer hair cells of the organ of Corti and vestibular type I hair cells are affected by these antibiotics. The access route to the hair cells and the sites and mechanisms of action of aminoglycosides are not precisely defined.

The uptake of tritiated tobramycin in 16th gd inner ears was studied. An initial rapid uptake of the drug, within 10 min, was followed by a slower accumulation, reaching a steady state after 60 min. Most of the tobramycin was bound reversibly, at least after a short period of incubation (2 h). The irreversibly bound fraction was of the same magnitude as the uptake within 10 min. Uptake took place against a concentration gradient.

The otocyst can differentiate even without the statoacoustic ganglion. The interaction of the sensory epithelium with the ganglion was investigated by explanting the statoacoustic ganglion without target tissue. Twenty-five percent of the ganglions survived and had outgrowth of neurites but there was no differentiation into either the cochlear or vestibular type of neuron cells.

Exposure of cultured otocysts (13 or 13.5 gd) to l-azetidine-2-carboxylic acid, a 1-proline analog that disrupts formation of collagen, resulted in retarded morphogenesis of the labyrinth and a dose- dependent derangement of the basal lamina.

The expression of intermediate filaments (IFs) was analysed using monoclonal antibodies. The same IF pattem was found in cultured inner ears as in vivo. Explants were taken on 13th, 15th or 16th gd. Exposure to gentamicin, ethacrynic acid or cisplatin did not alter the IF composition. Cytokeratins (CKs) 8 and 18 were identified in all inner ear epithelia. In addition CKs 7 and 19 were visualized in the epithelia involved in maintaining endolymph homeostasis. The ganglion cells showed coexpression of CK, vimentin and neurofilaments.

The elemental composition of the endolymph compartment of 16th gd inner ears cultured for 5 days was studied using energy-dispersive X-ray microanalysis. Na to K ratios characteristic of endolymph were found.

We have established an in vitro model of long-time culture of 4-day-old rat utricular maculae to study aminoglycoside-induced vestibular hair-cell renewal in the mammalian inner ear. The explanted maculae were cultured for up to 28 days on the surface of a membrane insert system. In an initial series of experiments utricles were exposed to 1 mM of gentamicin for 48 h and then allowed to recover in unsupplemented medium or in medium supplemented with the anti-mitotic drug aphidicolin. In a parallel control series, explants were not exposed to gentamicin. Utricles were harvested at specified time points from the second through the 28th day in vitro. Whole-mount utricles were stained with phalloidin-fluorescein isothiocyanate and their stereociliary bundles visualized and counted. In a second experimental series 2'-bromo-5'deoxyuridine labeling was used to confirm the antimitotic efficacy of aphidicolin. Loss of hair-cell stereociliary bundles was nearly complete 3 days after exposure to gentamicin, with the density of stereociliary bundles only 3-4% of their original density. Renewal of hair-cell bundles was abundant (i.e. 15x increase) in cultures in unsupplemented medium, with a peak of stereociliary bundle renewal reached after 21 days in vitro. A limited amount of hair-cell renewal also occurred in the presence of the anti-mitotic drug, aphidicolin. These results suggest that spontaneous renewal of hair-cell stereociliary bundles following gentamicin damage in utricular explants predominantly follows a pathway that includes mitotic events, but that a small portion of the hair-cell stereociliary bundle renewal does not require mitotic activity.

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.

OBJECTIVES/HYPOTHESIS: Data from patients registered for myringoplasty during 2002 to 2012 in the Swedish National Quality Registry for Myringoplasty.

STUDY DESIGN: Both conventional myringoplasty and fat-graft techniques were used aimed at healing the tympanic membrane in noninfected ears.

METHODS: Analysis was performed on data in a national database collected from 32 ear, nose, and throat clinics. Surgical procedures and outcomes, and patient satisfaction from a questionnaire were studied.

RESULTS: The database was comprised of 3,775 surgical procedures, with follow-up available for analysis. One-third were children under the age of 15 years. The most common indication for surgery was infection prophylaxis. The overall healing rate of the tympanic membrane after surgery was 88.5%, with a high mean patient satisfaction. Complications registered were postoperative infection, tinnitus, or taste disturbance that occurred in 5.8% of patients.

CONCLUSIONS: Swedish results for a large number of patients who completed myringoplasty are presented. The success rate in this study is comparable to other studies, and good patient-reported outcome measures of myringoplasty are presented. Databases for surgical procedures and clinical audits are systematic processes for continuous learning in healthcare. This study shows that clinical databases can be utilized to analyze national results of surgical procedures.

LEVEL OF EVIDENCE: 2b Laryngoscope, 127:2389-2395, 2017.

Objectives: To present hearing results after successful primary myringoplasty surgeries registered in the Swedish Quality Registry for Myringoplasty and to evaluate the chance of hearing improvement and the risk of hearing loss.

Design: A retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012.

Settings: Registry data from secondary and tertiary hospitals performing myringoplasty.

Participants: Patients with healed tympanic membrane after primary myringoplasty surgery performed from 2002 to 2012 in Sweden.

Main outcome measures: Postoperative hearing results, hearing gain and air-bone gap (ABG).

Results: In 2226 myringoplasties, air conduction audiograms were recorded, and the average preoperative pure tone average (PTA(4)) of the group was 28.5 dB, which improved postoperatively to 19.6 dB with an average of 8.8 dB improvement. Bone conduction was measured for 1476 procedures. Closure of the ABG to 10 dB or less was achieved in 51% of the ears and to less than 20 dB in 89% of the ears. Sixty-one percent of patients with preoperatively deteriorated hearing experienced improved hearing, but 3% of all patients experienced deteriorated hearing. After the surgery, 93% of the patients were satisfied.

Conclusions: Hearing results after successful myringoplasty surgery are often favourable, but although the tympanic membrane is healed, hearing improvement is not guaranteed, and hearing deterioration can also occur.

Background: The Swedish Quality Register for Ear Surgery (SwedEar) is a national register monitoring surgical procedures and outcomes of ear surgery to facilitate quality improvement. The value of the register is dependent on the quality of its data. SwedEar has never been validated regarding data quality or missing entries. Therefor, the purpose of this study was to assess coverage, completeness and response rate in the register and validate the physicians’ reported data accuracy.

Methods: In this validation study, the completeness, response rate and missing registrations were analysed. Data in SwedEar were compared with the yearly collected statistics of otosurgical procedures in The Swedish Otosurgical Society and the comparison of rates between groups was calculated with Fisher’s exact test. Validation of registered data accuracy was performed on every 20th registered case during a five-year period. Data were reabstracted from medical records and compared with the original registration. Interrater agreement, reliability measures, Cohen’s kappa, Gwet’s AC1 and positive predictive value were calculated.

Results: SwedEar has a coverage of 100%. The completeness of registered cases was 84% and the response rate was 74%. The validation of data accuracy assessed 13 530 variables, including audiograms. Less than 3% of incorrect or missing variables were identified. For most of the pre- and postoperative variables the Kappa and Gwet´s AC1 results show an almost perfect agreement (> 0.80). For audiogram data the ICC shows an excellent reliability (> 0.9) for all but one value.

Conclusion: This validation shows that SwedEar has excellent coverage, high completeness, and that the data in the register have almost perfect reliability. The data are suitable for both clinical and research purposes. Further efforts to improve completeness are warranted.

Objectives/Hypothesis: Postoperative tinnitus and taste disturbances after myringoplasty are more common than previously reported.

Study Design: This study was a retrospective analysis of prospectively collected data from the Swedish National Quality Registry for Myringoplasty.

Methods: The analysis was performed on extracted data from all counties in Sweden collected from database A from 2002 to 2012 and database B from 2013 to 2016. Tinnitus and taste disturbance complications 1 year after myringoplasty were analyzed in relation to gender, age, procedure, and success rate. In database A, physicians reported tinnitus and taste disturbances. In database B, patients reported the complications.

Results: A major difference was found when the complications were reported by physicians compared to when the complications were reported by patients. In database A, tinnitus was reported in 1.2% of the patients and taste disturbances in 0.5%. In database B, the frequencies were 12.3% and 11.2%, respectively. Tinnitus and taste disturbances were more frequent after conventional myringoplasty compared to those after fat grafting and were more frequent after primary compared to those after revision surgery when reported by physicians. Patients, however, reported the same frequency of tinnitus after fat graft myringoplasty compared to that after conventional myringoplasty (12.0% vs. 12.6%) and fewer taste disturbances after revision surgery. In follow‐up assessments, complications persisted after surgery over a long time period.

Conclusion: Tinnitus and taste disturbances are more common after myringoplasty when patients report their symptoms than when physicians report the symptoms.

Cutaneous reparative processes, including wound healing, are highly developed procedures in which a chain of actions occurs to reconstitute the function of the wounded tissue. To prevent a delayed or excessive reparative process it is important to understand how this procedure develops and is maintained. One of the major extracellular matrix components of the skin is the glycosaminoglycan hyaluronan (HA). HA contributes to an extracellular environment, which is permissive for cell motility and proliferation, features that may account for HA’s unique properties observed in scarless foetal wound healing. The molecule is found at high concentration whenever proliferation, regeneration and repair of tissue occur.

The aims of the present studies were to analyse the distribution of HA and to investigate its possible role in various cutaneous conditions associated with an impaired reparative process like in scar tissue formation in healing wounds, changed skin characteristics in diabetes mellitus and proliferating activity in basal cell carcinomas.

Tissue biopsies were obtained from healthy human skin, type-I diabetic skin and various scar tissues. The samples were analysed in the light microscope with a hyaluronan-binding-probe, antibodies for collagen I, III, PCNA and Ki-67. Ultrastructural analyses were performed on the same tissue samples.

In normal skin HA was present mainly in the papillary dermis. In epidermis HA was located in between the keratinocytes in the spinous layer. In the different scar tissues the localization of HA varied, with an HA distribution in mature scar type resembling that in normal skin. In keloids the papillary dermis lacked HA, but the thickened epidermis contained more HA than the other scar types. Ultrastructural studies of keloids revealed an altered collagen structure in the dermal layers, with an abundance of thin collagen fibers in the reticular dermis and thicker collagen fibers in the papillary dermis. Furthermore, the keloids displayed epidermal changes, which involved the basement membrane (BM), exhibiting fewer hemidesmosomes, and an altered shape of desmosomes in the entire enlarged spinous layer. These alterations in epidermis are suggested to influence the hydrodynamic and cell regulatory properties of the wounded skin.

In diabetic patients, a reduced HA staining in the basement membrane zone was seen. The staining intensity of HA correlated to the physical properties of the skin reflected by their grades of limited joint mobility (LJM). Furthermore, the HA staining correlated with serum concentration of the HbA1c.

In basal cell carcinomas (BCC), HA occurred predominantly in the tumour stroma. The distribution was most intense in the highly developed superficial BCC type, and resembled that of the papillary dermis of normal skin. In contrast, in the infiltrative BCC type, the tumour stroma stained weakly in the infiltrative part of the tumour. Moreover, the surrounding dermal layer was deranged and devoid of HA. The findings suggest that the tumour stroma in superficial BCC causes a slow, well-regulated cell growth in which the tumour cells do not substantially disturb the normal skin function. In the infiltrative BCC type, the tumour cells cause a disintegration of the tumour stroma as well as the normal surrounding dermis, which permits further spreading of the tumour. In fact, the behaviour of the infiltrative BCC tumour, growing beyond its boundaries, resembles that of the keloid.

The mapping of the distribution of HA could be a useful tool for prognostic information, for evaluating the degree of progress and for deciding the choice of treatment in various diseases of the skin. In skin malignancies such as BCC it can be used to determine the radicality at the surgical excision of the tumour.

Keywords: Hyaluronan, scar tissue, diabetes mellitus, basal cell carcinoma, skin, wound healing

Glycosaminoglycans are important components of all extracellular matrices. One of the glycosaminoglycans is hyaluronan, which is ubiquitously distributed throughout the connective tissue. Hyaluronan is especially abundant in the skin, in which it is of both structural and functional importance. This study describes the localization and distribution of hyaluronan in the skin of healthy individuals and of 23 patients with insulin-dependent diabetes mellitus and various degrees of limited joint mobility. In normal skin, hyaluronan staining was seen in all layers but most prominently in the papillary dermis and the basement membrane zone. In the skin from diabetic patients with normal or only moderately restricted mobility of the hands (limited joint mobility grades 0 and 1), the distribution of hyaluronan was similar to that of normal skin. In the skin of patients with severe restriction in joint mobility (limited joint mobility grade 2) the staining pattern was significantly different with weak hyaluronan staining in the papillary dermis and the basement membrane zone almost devoid of hyaluronan. Moreover, an increased epidermal thickness in the latter patients was evident as well as a pronounced hyaluronan staining compared with normal epidermis.