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Abstract Background Selection of the best medical students among applicants is debated and many different methods are used. Academic merits predict good academic performance, but students admitted by other pathways need not be less successful. The aim of this study, was to compare communication skills between students admitted to medical school through interviews or on academic merits, respectively. Methods A retrospective cohort study. Communication skills at a surgical OSCE in 2008 were assessed independently by two observers using an evaluative rating scale. Correlations, t-tests and multivariate analyses by logistic regressions were employed. Academic merits were defined as upper secondary school grade point average (GPA) or scores from the Swedish Scholastic Assessment Test (SweSAT). Results The risk of showing unsatisfactory communicative performance was significantly lower among the students selected by interviews (OR 0.32, CI95 0.12-0.83), compared to those selected on the basis of academic merits. However, there was no significant difference in communication skills scores between the different admission groups; neither did the proportion of high performers differ. No difference in the result of the written examination was seen between groups. Conclusions Our results confirm previous experience from many medical schools that students selected in different ways achieve comparable results during the clinical semesters. However, selection through interview seems to reduce the number of students who demonstrate inferior communication skills at 4th year of medical school.

Background: In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years., Material and Method: This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included., Results: During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001)., Conclusions: We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Talani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are malnourished at diagnosis. In this study, we investigated how pretreatment body mass index (BMI) and fat-free mass index (FFMI) correlate with early death, and whether these measurements are useful markers of prognosis for risk stratification of head and neck cancer patients., Methods: Patients (n = 404) with newly diagnosed, curable HNSCC and WHO performance status 0-2 were prospectively included and met with a study representative before treatment initiation, as well as up to four follow-up visits. All patients provided an estimate of body weight at 6 months prior to diagnosis. Bioelectrical impedance analysis (BIA) was performed for all patients before treatment initiation., Results: Most patients had oropharyngeal (46%), oral cavity (28%), or laryngeal cancer (12%). Forty-five (11%) patients met the standardized criteria for malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) at diagnosis. FFMI at diagnosis was lower in patients who died within 6 and 12 months after the start of treatment than in patients who survived these time points (p = 0.035 and p = 0.005, respectively)., Conclusions: In this study, pretreatment FFMI was an independent prognostic factor for death within 6 and 12 months after the start of treatment in patients with HNSCC. Pretreatment BMI was not an independent risk factor for death within 6 and 12 months after treatment termination. Thus, FFMI may be useful for risk stratification of patients with head and neck cancer., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated., Material and Methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition., Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively ( n  = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16-. 5-year overall survival (OS) was 68% (95% CI: 64-72%), with76% and 37% for p16+ patients and p16- patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II-III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone., Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16- tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.

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., (© 2021 Wiley Periodicals LLC.)

Introduction  Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective  The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods  A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results  Two-hundred and sixty HNCUP patients were included. The tumors were HPV-positive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age ( p  < 0.001), performance status ( p = 0.036), and N stage ( p = 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions  Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and (chemo) radiation and primary (chemo) radiation gave similar survival outcomes. A randomized treatment study that includes quality of life is needed to establish the optimal treatment., Competing Interests: Conflict of Interest Dr. Axelsson reports grants from The Foundation ACTA Oto-Laryngologica, The Health and Medical Care Committee of the Regional Executive Board, Region VästraGötaland, and from The ALF project funding for clinically oriented medical research projects, during the conduct of the study. Dr. Hammerlid reports grants from The Health and Medical Care Committee of the Regional Executive Board, Region VästraGötaland, and from The ALF project funding for clinically oriented medical research projects, during the conduct of the study., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: The five Nordic countries with a population of 27M people form a rather homogenous region in terms of health care. The management of Head and Neck Cancer (HNC) is centralized to the 21 university hospitals in these countries. Our aim was to survey the current status of organization of palliative care for patients with HNC in the Nordic countries as the field is rapidly developing., Materials and Methods: A structured web-based questionnaire was sent to all the Departments of Otorhinolaryngology-Head and Neck Surgery and Oncology managing HNC in the Nordic countries., Results: All 21 (100%) Nordic university hospitals responded to the survey. A majority (over 90%) of the patients are discussed at diagnosis in a multidisciplinary tumor board (MDT), but the presence of a palliative care specialist is lacking in 95% of these MDT's. The patients have access to specialized palliative care units (n = 14, 67%), teams (n = 10, 48%), and consultants (n = 4, 19%) in the majority of the hospitals., Conclusion: The present results show that specialized palliative care services are available at the Nordic university hospitals. A major finding was that the collaboration between head and neck surgeons, oncologists and palliative care specialists is not well structured and the palliative care pathway of patients with HNC is not systematically organized. We suggest that early integrated palliative care needs to be included as an addition to the already existing HNC care pathways in the Nordic countries.

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., (© 2020 Wiley Periodicals, Inc.)

Background: Cancers of the head and neck have a high mortality rate, and roughly 10% of the patients die within six months of diagnosis. To our knowledge little has been written about this group. We wished to identify risk factors for early death, to predict and monitor patients at risk better and, if possible, avoid unjustified major treatment., Methods and Findings: This population-based nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included data from 2008-2015 and 9733 patients at potential risk of early death. A total of 925 (9.5%) patients died within six months. For every year older the patients became, the risk of early death increased by 2.3% (p<0.001). The relative risk of death was 3.37 times higher (237%) for patients with WHO score 1 compared with WHO score 0. A primary tumour in the hypopharynx correlated with a 24% increased risk over the oral cavity (p<0.024). Patients with stage IV disease had a 3.7 times greater risk of early death than those with stage I (p<0.001). As expected, a 12 times increased risk of early death was noted in the palliative treatment group, compared to the curative group. Limitations to this study were that the actual cause of death was not recorded in the SweHNCR, and that socioeconomic factors, alcohol consumption, smoking habits, and HPV status, were not reported in SweHNCR until 2015. However, the fact that this is a population-based nationwide study including 9733 patients compensates for some of these limitations., Conclusions: Identification of patients at increased risk of early death shows that older patients with advanced disease, increased WHO score, primary tumour in the hypopharynx, and those given palliative treatment, are more likely than the others to die from head and neck cancer within six months of diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We aimed to obtain information on the number of Nordic centers performing tracheal resections, crico-tracheal resections, and laryngo-tracheal reconstructions, as well as the patient volume and the standard regimens associated with these procedures., Methods: Consultants at all Departments of Otorhinolaryngology-Head and Neck Surgery (ORL-HNS, n = 22) and Thoracic Surgery (n = 21) in the five Nordic countries were invited (April 2018-January 2019) to participate in an online survey., Results: All 43 departments responded to the survey. Twenty departments declared to perform one or more of the three types of tracheal resections. At five hospitals, departments of ORL-HNS and Thoracic Surgery perform these operations in collaboration. Hence, one or more of the tracheal operations in question are carried out at 15 centers. The median annual number of tracheal operations per center is five (range 1-20). Great variations were found regarding contraindications (relative and absolute) for surgery, the use of guardian sterno-mental sutures (all patients, 33%; selected cases, 40% of centers), prophylactic antibiotic therapy (cefuroxime +/- metronidazole, penicillin +/- metronidazole, clindamycin, imipenem, or none), post-operative follow-up time (range: children: 3-120 months; adults: 0-60 months), and the performance of post-operative bronchoscopy., Conclusions: Fifteen centers each perform a low number of annual operations with significant variations in the selection of patients and the clinical setup, which raises the question if a higher degree of collaboration and centralization would be warranted. We encourage Nordic transnational collaboration, pursuing alignment on central management issues, and establishment of a common prospective database for future tracheal resection surgery.

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) tumors are often resistant to therapies. Therefore searching for predictive markers and new targets for treatment in clinically relevant in vitro tumor models is essential. Five HNSCC-derived cell lines were used to assess the effect of 3D culturing compared to 2D monolayers in terms of cell proliferation, response to anti-cancer therapy as well as expression of EMT and CSC genes., Methods: The viability and proliferation capacity of HNSCC cells as well as induction of apoptosis in tumor spheroids cells after treatment was assessed by MTT assay, crystal violet- and TUNEL assay respectively. Expression of EMT and CSC markers was analyzed on mRNA (RT-qPCR) and protein (Western blot) level., Results: We showed that HNSCC cells from different tumors formed spheroids that differed in size and density in regard to EMT-associated protein expression and culturing time. In all spheroids, an up regulation of CDH1, NANOG and SOX2 was observed in comparison to 2D but changes in the expression of EGFR and EMT markers varied among the cell lines. Moreover, most HNSCC cells grown in 3D showed decreased sensitivity to cisplatin and cetuximab (anti-EGFR) treatment., Conclusions: Taken together, our study points at notable differences between these two cellular systems in terms of EMT-associated gene expression profile and drug response. As the 3D cell cultures imitate the in vivo behaviour of neoplastic cells within the tumor, our study suggest that 3D culture model is superior to 2D monolayers in the search for new therapeutic targets.

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53β, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53β revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53β as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.

Chemoresistant cancer cells express high levels of aldehyde dehydrogenases (ALDHs), particularly in head and neck squamous cell carcinoma (HNSCC). The ALDH family of enzymes detoxify both exogenous and endogenous aldehydes. Since many chemotherapeutic agents, such as cisplatin, result in the generation of cytotoxic aldehydes and oxidative stress, we hypothesized that cells expressing high levels of ALDH may be more chemoresistant due to their increased detoxifying capacity and that inhibitors of ALDHs may sensitize them to these drugs. Here, we show that overall ALDH activity is increased with cisplatin treatment of HNSCC and that ALDH3A1 protein expression is particularly enriched in cells treated with cisplatin. Activation of ALDH3A1 by a small molecule activator (Alda-89) increased survival of HNSCC cells treated with cisplatin. Conversely, treatment with a novel small molecule ALDH inhibitor (Aldi-6) resulted in a marked decrease in cell viability, and the combination of Aldi-6 and cisplatin resulted in a more pronounced reduction of cell viability and a greater reduction in tumor burden in vivo than what was observed with cisplatin alone. These data indicate that ALDH3A1 contributes to cisplatin resistance in HNSCC and that the targeting of ALDH, specifically, ALDH3A1, appears to be a promising strategy in this disease., Competing Interests: CONFLICTS OF INTEREST DM-R and C-HC are co-founders of ALDEA Pharmaceuticals. However, none of the research in the DM-R lab (of which C-HC is a member) is discussed with, supported by or is in collaboration with the company.