No description available.

No description available.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13258号 / 論医博第2176号 / 新制||医||1037(附属図書館) / (主査)教授 別所 和久, 教授 武藤 学, 教授 小西 靖彦 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bei dieser Arbeit handelt es sich um eine retrospektive Studie bezüglich Inzidenz und Therapie von Mundhöhlen- und Oropharynxkarzinomen, welche in dem Zeitraum von 1993 bis 2009 in der HNO-Klinik der Universität Leipzig als „High Volume Center“ behandelt wurden, mit besonderem Augenmerk auf die Stadien III-IV nach UICC/AJCC. In unserer Studie konnten wir eine Zunahme der an der Universität in Leipzig registrierten Patienten mit Mundhöhlen- und Oropharynxkarzinomen über die Jahre 1993 bis 2009 verzeichnen. Männer waren mehr als fünfmal so häufig betroffen wie Frauen. Diese Verteilung hielt sich über den Beobachtungszeitraum konstant. Bei den weiblichen Patientinnen wurden im Durchschnitt niedrigere Tumorstadien bei Erstdiagnose festgestellt. Frauen hatten insgesamt eine höhere 5-Jahresüberlebensrate. Die Stadienverteilung nach UICC/AJCC bei Erstdiagnose eines Mundhöhlen- und Oropharynxkarzinoms blieb über die Jahre hinweg annähernd gleich. Es wurden meist hohe Stadien festgestellt (62,7% Stadium IV). Das mittlere Erkrankungsalter von Mundhöhlen- und Oropharynxkarzinomen sank über den Beobachtungszeitraum. Das Alter bei Rezidivmanifestation blieb allerdings über die Jahre gleich und lag unter dem durchschnittlichen Alter bei Erstdiagnosestellung. In diesem Zeitraum wird in der Literatur eine zunehmende Infektionsrate mit HPV beschrieben, welche gemäß der Literaturdaten mit einem jüngeren Erkrankungsalter einhergeht. Über die Jahre fanden wir in dem von uns untersuchten Patientenkollektiv der Universitätsklinik Leipzig eine stetige Verbesserung der mittleren Überlebensraten. In zeitlicher Assoziation zu dieser Entwicklung fand eine Änderung der Therapiemodalitäten insbesondere mit Einführung der systemischen Chemotherapie ab ca. 2004 in Richtung einer zunehmenden multimodalen Therapie statt. Es konnte ein Vorteil im Gesamtüberleben nach einer kombiniert-operativen Therapie mit adjuvanter Radiochemotherapie gegenüber allen anderen Therapieformen gezeigt werden. Insbesondere im Stadium IV nach UICC/AJCC zeigte sich ebenfalls ein Vorteil der kombinierten Radiochemotherapie gegenüber einer alleinigen Radiotherapie.

Background: Patients with head and neck cancer (HNC) carry a clinically significant symptom burden, alterations in function (e.g. impaired ability to chew, swallow, and talk), and decrease in quality of life. Furthermore, treatment impacts social activities and interactions as patients report reduced sexuality and high rates of depression. Patients may suffer undue anxiety because they find treatment incomprehensible, which is partially a function of limited, understandable information. This can be particularly challenging for patients with limited health literacy. Furthermore, a globalized world consisting of cultural differences increases the need to enhance transparent communication of risk. Research on risk literacy and medical decision-making validates that across different cultures, people often have severe obstacles in grasping a host of prerequisite concepts for understanding health-related risk information such as numbers, graphs, and basic medical facts. Patients’ perceptions of having obtained adequate information prior and during treatment are predictive of positive outcomes. Providing patient-centered decision-support, utilizing visual images, may increase understanding of treatment options and associated risks to improve satisfaction with their decision and consultation, while reducing decisional conflict. A scoping review was conducted on electronic, decision aids (DAs) for oncology patients that returned 4217 articles, but only 167 for HNC, with 12 meeting the inclusion criteria. Three themes were identified: (1) both patients and physicians valued the DA; (2) DAs should be visually supported by images; and (3) use of a DA lessened decisional conflict and anxiety while improving knowledge, satisfaction and shared decision-making. This informed the design of a prototype DA. Semi-structured interviews were conducted with 12 survivors of HNC who completed treatment at BC Cancer- Victoria on their experiences, feedback on the utility of a DA, and insights into design features. Thematic analysis resulted in 12 themes that were organized into 3 categories. The first category, “the patient experience,” included three themes: “patients have high, through varying information needs”; “an emotional experience”; and “stories of coping, strength and resiliency.” The second category, “electronic DAs and decision support,” also included three themes: “familiarity with decision aids”; “support of concept: usefulness and of visual aids”; and “versatility of the prototype.” The last category, “evaluation of prototype”, contained six themes: “reaction to prototype”; “favourited features”; “complexity”; “preference for customizability”; “suggestions for improvement”; and “presentation device.” Key Message: The use of DAs have been shown to better inform and increase patients’ knowledge, accuracy of risk perception, and congruency between informed values and care choices allowing them to take part in active decision-making, compared to usual care. Survivors of HNC were in unanimous support of using visual images to help explain treatment and assist in decision making on treatment options. Furthermore, they contributed invaluable feedback on the prototype design, demonstrating the value of a co-design methodologies. / Graduate

No description available.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy associated with molecular heterogeneity, locoregional spread, resistance to therapy and relapse after initial treatment. Increasing evidence suggests that master developmental pathways with key roles in adult tissue homeostasis, including Hippo and Wnt/β-catenin signaling, are dysregulated in the initiation and progression of HNSCC. However, a comprehensive investigation into the crosstalk between these pathways is currently lacking, and may prove crucial to the discovery of novel targets for HNSCC therapy. More recent evidence points to the tumor microenvironment, mainly comprising cancer-associated fibroblasts (CAFs), as capable of influencing tumor cell behavior and promoting invasive HNSCC phenotypes. Nonetheless, current methods to screen for CAF markers in tumors are restricted to targeted immunostaining experiments with limited success and robustness across tissue types. The Cancer Genome Atlas network has generated multi-tiered molecular profiles for over 10,000 tumors spanning more than two dozen different cancer types, providing an unprecedented opportunity for the application and development of integrative methods aimed at the in silico interrogation of experimentally-derived signatures. These multi-omic profiles further enable one to link genomic anomalies, including somatic mutations and DNA copy number alterations, with phenotypic effects driven by pathogenic pathway activity. Effectively querying this vast amount of information to help elucidate subsets of functionally and clinically-relevant oncogenic drivers, however, remains an ongoing challenge. To address these issues, I first investigate the effects of oncogenic pathway perturbation in HNSCC using experimental models coupled with in vitro genome-wide transcriptional profiling. Next, I describe a new computational approach for the unbiased identification of CAF markers in HNSCC solely using bulk tumor RNA-sequencing information. Lastly, I have developed Candidate Driver Analysis or CaDrA - a statistical framework that allows one to query genetic and epigenetic alterations for candidate drivers of signature activity within a given disease context. Collectively, this work offers new perspectives on the molecular cues underlying HNSCC development, while simultaneously highlighting the power of integrative genomics methods capable of accelerating the discovery of novel targets for cancer diagnosis and therapy.

abstract: Recent studies have shown that human papillomavirus (HPV) plays a role in development of cancers, one of which is head and neck cancer. There is strong and consistent molecular evidence demonstrating that human papillomavirus (HPV) is an etiological cause of these oropharyngeal cancers. Despite the introduction of HPV vaccines, there is still an increase in human papillomavirus associated OPC (HPVOPC) and it is expected that the incidence of head and neck cancer, specifically oropharyngeal cancer (OPC) will increase. The aim of this study is to utilize human papillomavirus (HPV) seropositivity for rapid detection of HPV early specific antigen-antibodies using a lateral flow assay. Human papillomavirus (HPV) 16 proteins of interest, E7, E6 and CE2 were expressed and purified in E. coli for detection of specific antibodies using lateral flow assay because viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer. 17 samples and 5 controls with already known antibody reactivity from ELISA analysis were selected for HPV serologic responses. The lateral flow strip was evaluated for its color band intensity using Image J software. Peak area was used to quantify the color intensity of the lateral flow strip. Out of the 17 samples, 11 (64.7%) showed high antibody levels to E7, 12 (70.6%) showed high Ab levels to E6 and 6 (35.3%) showed high Ab levels to CE2. Correlation coefficient between antibody detection by sight and ELISA for E7, CE2 and E6 were 0.6614, 0.4845 and 0.2372 respectively and correlation coefficient between lateral flow assay and ELISA for E7, CE2 and E6 were 0.3480, 0.1716 and 0.1644 respectively. This further proves patients or samples with HPV 16 oropharyngeal cancer have detectable antibodies to early E7, E6 and E2 proteins, which are potential biomarkers for HPV-associated oropharyngeal cancer. / Dissertation/Thesis / Masters Thesis Molecular and Cellular Biology 2019

Bakgrund: Huvud- och halscancer leder till olika förändringar som påverkar patienten fysiskt och psykiskt samt påverkar vardagen och livssituationen. Sjuksköterskan har en central roll för dessa patienter då dennes uppgift är att främja hälsa genom att bidra med stödåtgärder. Mer kunskap om hur patienterna upplevelser förändringar efter huvud- och halscancer krävs för att kunna ge adekvata omvårdnadsåtgärder.Syfte: Syftet var att beskriva patienters upplevelser av förändringar i utseende och funktion under och efter behandling av huvud- och halscancer. Metod: En litteraturöversikt med kvalitativa artiklar genomfördes utifrån tolv artiklar från databaserna Medline och Cinahl. Dataanalysen genomfördes enligt Fribergs femstegsmodell. Resultat: Litteraturöversiktens resultat bestod av tre kategorier och sju subkategorier. Kategorierna var förändringar av kroppens funktioner, förändringar i utseende och förändringar i sociala sammanhang. Resultatet visade att patienterna upplevde svårigheter att äta och konsekvenserna det ledde till. Patienterna upplevde också utseendeförändringar och att deras sociala liv påverkades.Slutsats: Patienternas liv förändrades negativt på olika sätt och ur olika aspekter. De hade svårigheter att äta, drabbades av utseendeförändringar och upplevde en påverkan på deras sociala liv. Sjuksköterskor kan erbjuda adekvata omvårdnadsinsatser till dessa patienter genom att vara lyhörd kring de förändringar som huvud- och halscancer medför. / Background: Head and neck cancer (HHC) leads to various changes which affect the patient physically and psychologically, but also the life situation. Nurses have a central role in promoting health and providing support to this patient group. More knowledge about patients’ experiences of changes after HHC is needed to offer adequate nursing interventions.Aim: The aim was to describe patients' experiences of changes in appearance and function during and after treatment for head and neck cancer. Method: A literature review with qualitative articles was carried out based on twelve articles retrieved from Medline and Cinahl. The data analysis was carried out according to Friberg's five-step model. Result: The result of the literature review consists of three categories and seven subcategories. The categories were Changes in the body's functions, Changes in appearance, and Changes in social contexts. The results showed that HHC patients experienced difficulties in eating and the consequences it led to. It also showed how patients experienced negative changes in their appearance. Furthermore, the patients experienced a negative impact on their social life.Conclusion: The patients' lives changed in different ways and from different aspects in a negative way. The patients had difficulties eating, suffered from changes in appearance, and experienced an impact on their social life. Nurses can offer adequate nursing interventions to these patients by being responsive to the changes.

Introduction: Oropharyngeal cancer (OPC) is a highly prevalent malignancy worldwideaffecting the tonsils, the soft palette and the base of the tongue. OPC has a high risk ofrecurrence. Patients are offered a 5-year follow-up program in order to discover earlyrecurrences. However, there exists some controversy regarding the benefit of this follow-up indetecting early recurrences. Objective: The primary aim of this study was to investigate whether recurrences of OPC weredetected in patient-initiated appointments or during routine follow-up. The secondary aim wasto compare the survival between these groups. Method and materials: This study is a retrospective cohort study regarding recurrencedetection among patients diagnosed with OPC. The Örebro Head- and neck cancer registerwas used to identify patients with recurrence of OPC. Additional data was collected frommedical records. Results: A total of 75 patients were included. Routine follow-up detected 50.7% ofrecurrences while patient-initiated visits detected 42.7% of recurrences. No statisticallysignificant difference was found in survival between these groups Conclusion: In contradiction to our hypothesis most of the recurrences were detected atroutine follow-up. There was no statistically significant difference in survival between thetwo ways of detection. These results indicate that our current follow-up program has animportance in detecting early recurrences and should not be altered.