Head and neck cancers are etiologically associated with smoking and alcohol consumption. Part of these tumors is induced by HPV and their incidence is increasing in the last decade. Patients with virally induced tumors have better prognosis even though they are usually diagnosed with tumors in advanced stage. One of the possible explanations may be better stimulation of the immune system by viral antigens. Macrophages are cells of the innate immune system which belong to professional phagocytes. They are called TAM upon infiltration to the tumor where they represent heterogeneous group of cells. Two main phenotypes are antitumor M1 and protumor M2 macrophages. TAMs are a major component of tumor microenvironment of many types of tumors, one of them are also head and neck cancers. In my thesis I focused on the immunohistochemical detection of M1 and M2 macrophages in the head and neck tumors of viral and non-viral etiology and at the same time RT-qPCR analyses of gene expression of macrophage-associated and/or immunosuppressive genes IDO1, ARG1, CD163, NOS2 a PTGS2 was performed. My data showed that HPV- negative tumors had higher number of M2 macrophages with typical markers CD163, ARG1 and PTGS2. It is known that patients with these tumors have worse prognosis of the disease. Due to high...

Background: This prospective study was conducted to assess changes in quality of life (QoL) of patients who undergo a partial laryngectomy (PLE). Methods: The European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-H&N35 were used pre-procedure (n=218), one week (n=159), three months (n=122) and one year after PLE (n=88). Changes over time were analyzed with the Wilcoxon-signed-rank-test and the Holm-Bonferroni-method, and interpreted regarding clinical relevance. Results: Most subscales worsened one week post-procedure, but many recovered to baseline level after one year. Dyspnea and cognitive functioning deteriorated over time, with worst scores recorded after one year. Financial difficulties and fatigue increased after surgery and maintained that level throughout the follow-up period; sticky saliva remained worse than at baseline, despite some improvements over time. Conclusions: The discovered limitations of QoL should be observed more closely during follow-up treatment, and patients should be informed about these potential eaffects before PLE.:1 Einführung ........................................................................................................... 3 1.1 Das Larynxkarzinom ......................................................................................... 3 1.2 Therapiemöglichkeiten des Larynxkarzinoms ................................................... 4 1.3 Lebensqualität ................................................................................................... 5 1.4 Methodik bei der Evaluierung von Lebensqualität ............................................. 7 1.5 Lebensqualität bei Krebspatienten .................................................................... 8 1.6 Lebensqualität nach Therapie von Kopf-Hals-Tumoren .................................. 10 2 Zielstellung der Studie ....................................................................................... 13 3 Publikation ......................................................................................................... 14 4 Zusammenfassung ............................................................................................ 37 4.1 Einführung....................................................................................................... 38 4.2 Methoden ........................................................................................................ 39 4.3 Ergebnisse ...................................................................................................... 39 4.4 Diskussion....................................................................................................... 41 5 Literaturverzeichnis ............................................................................................ 44 6 Anlagen ............................................................................................................. 49 6.1 Darstellung des eigenen Beitrags ................................................................... 49 6.2 Selbstständigkeitserklärung ............................................................................ 50

Regionäre Metastasten verschlechtern die Prognose von Patienten mit einem Kopf-Hals-Karzinom deutlich. So verringert sich die 5-Jahresüberlebensrate bei einer Metastasierung in die regionären Lymphknoten um etwa 50%. Die Daten von 672 Patienten mit einem Plattenepithelkarzinom des Oropharynx, Hypopharynx oder Larynx der Jahre 2005 bis 2009 wurden retrospektiv ausgewertet. Bei 270 Patienten mit einem Primärtumor der Tonsille (n=82), des Oropharynx (excl. Tonsille) (n=70), des Hypopharynx (n=33), der Supraglottis (n=42) oder der Glottis (n=43) wurde eine ipsilaterale (n=47) oder bilaterale (n=223) Neck dissection im Rahmen der Primärtherapie durchgeführt. Dabei wurden bei 61% der ipsilateralen und 49% der kontralateralen Neck dissections die Level en bloc reseziert und konnten im Falle einer Metastasierung nicht in die levelbezogene Auswertung eingeschlossen werden. Die Level, in welche die Tumoren bevorzugt metastasieren, wurden evaluiert und tumorspezifische Parameter (Tumorlokalisation, pT-Kategorie) auf ihren möglichen Einfluss auf die Parameter der Metastasierung (pN-Kategorie, Seitenlokalisation, Anzahl, Größe und Level der Lymphknotenmetastasen) getestet. In allen untersuchten Tumorlokalisationen lagen die meisten Lymphknotenmetastasen im ipsi- und kontralateralen Level II. Bei Angabe der Sublevel lagen die Metastasen vor allem in Level IIA. Ipsilateral konnten Lymphknotenmetastasen in allen fünf Leveln und kontralateral in den Leveln II, III und V nachgewiesen werden. Verschiedene Metastasierungswege und Levelkombinationen der Lymphknotenmetastasen zeigen, dass die regionäre Metastasierung keinen starren Gesetzmäßigkeiten folgt. Die Metastasierungsrate und die Seitenlokalisation der Lymphknotenmetastasen unterschieden sich signifikant je nach Lokalisation des Primärtumors. Die Anzahl der ipsilateralen histopathologisch nachgewiesenen Lymphknoten zeigte eine statistisch signifikante Korrelation zum Nachweis von Lymphknotenmetastasen. Eine zunehmende Metastasierung mit steigender pT Kategorie wurde bei den Glottistumoren nachgewiesen, nicht aber bei den Tumoren der anderen Lokalisationen. Die Ausdehnung des Primärtumors (pT-Kategorie) lässt keine Rückschlüsse auf die Parameter regionärer Metastasen (Seitenlokalisation, Anzahl, Größe und Level der Lymphknotenmetastasen) zu.

Contexte : Le rôle de l’exposition professionnelle aux solvants dans la survenue de cancers des voies aéro-digestives supérieures (VADS), suggéré dans quelques études, n’a été que peu examiné, malgré leur utilisation très répandue en milieu de travail. Objectif : L’objectif de cette thèse état d’évaluer les associations entre les expositions professionnelles aux solvants et le risque de cancer des VADS. Méthodes : Ce travail est basé sur les données de l’étude Icare, une large étude cas-témoins en population générale conduite en France entre 2001-2007. L’analyse a été restreinte aux hommes et a porté sur 1857 cas de carcinome épidermoïde de la cavité buccale, du pharynx et du larynx, et 2780 témoins. L’histoire professionnelle détaillée ainsi que les consommations de tabac et d’alcool ont été recueillies par questionnaire. Les expositions aux solvants ont été évaluées à l’aide de matrices emplois-expositions et incluaient cinq solvants chlorés (perchloroéthylène, trichloroéthylène, chlorure de méthylène, chloroforme, tétrachlorure de carbone), cinq solvants pétroliers (benzène ; essences carburant ; gazole, fiouls et kérosène ; essences spéciales ; white spirits) et cinq solvants oxygénés (cétones et esters ; alcools ; éther éthylique ; éthylène glycol ; tétrahydrofurane). Les odds-ratios ajustés sur les consommations de tabac et d’alcool et d’autres facteurs de confusion potentiels, et les intervalles de confiances à 95% ont été estimés par régression logistique. Résultats : Aucune association significative n’a été mise en évidence entre exposition professionnelle aux solvants chlorés, pétroliers et oxygénés étudiés et le risque de cancer de l’ensemble des VADS. Dans l’analyse par localisation, le risque de cancer du larynx augmentait significativement avec l’exposition cumulée au perchloroéthylène. Des risques élevés de cancer de l’hypopharynx, bien que non significatifs, étaient observés pour les hommes exposés à des niveaux élevés de chlorure de méthylène, de white spirits et de tétrahydrofurane. Une association entre exposition au tétrahydrofurane et cancer de la cavité buccale était également suggérée. Aucune association claire n’était observée pour les autres solvants, quelle que soit la localisation de cancer. Conclusion : Des associations positives ont été observées avec plusieurs solvants spécifiques. Toutefois, dans l’ensemble, nos résultats ne sont pas en faveur d’un rôle majeur de l’exposition aux solvants dans la survenue de cancer des VADS. / Background : The role of occupational exposure to solvents in the risk of head and neck cancer has been suggested in some studies but has been few investigated, despite their widespread use in the workplace. Objective: The objective of this thesis was to examine the associations between occupational exposure to solvents and the risk of head and neck cancer. Methods: This work is based on data from the ICARE study, a large population-based case-control study conducted in France between 2001 and 2007. The analysis was restricted to men and included 1,857 cases of squamous cell carcinoma of the oral cavity, pharynx and larynx and 2,780 controls. Detailed occupational lifetime as well as alcohol and tobacco consumptions were collected by questionnaires. Exposure to solvents was assessed by job exposure matrices and included five chlorinated solvents (perchloroethylene, trichloroethylene, methylene chloride, chloroform, carbon tetrachloride), five petroleum-based solvents (benzene; gasoline; diesel, fuels and kerosene; special petroleum products; white spirits) and five oxygenated solvents (ketones and esters; alcohols; diethyl ether; ethylene glycol; tetrahydrofuran). Odds-ratios adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals were estimated with logistic models. Results: No significant association was found between occupational exposure to chlorinated, petroleum-based and oxygenated solvents and the risk of head and neck cancer overall. In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to perchloroethylene. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of methylene chloride, white spirits and tetrahydrofuran. An association between exposure to tetrahydrofuran and oral cavity cancer was also suggested. No other clear association was found for the other solvents under study, for any cancer site. Conclusion: Although positive associations were observed for several solvents, overall the results do not suggest a substantial role of exposure to solvents in head and neck cancer risk.

Context: Medical management for head and neck cancer (HNC) often includes neck dissection surgery, a side effect of which is shoulder dysfunction. There is no consensus for which patient-reported outcome measure (PRO) is most appropriate to quantify shoulder dysfunction in this population. Objective: The aims of this research study were to: (1) use Rasch methodologies to assess construct validity and overall appropriateness of test score interpretation of Disability of the Arm, Shoulder and Hand (DASH), QuickDASH, Shoulder Pain and Disability Index (SPADI) and Neck Dissection Impairment Index (NDII) in the HNC population; (2) determine appropriateness of use of University of Washington Quality of Life (UW-QoL) shoulder subscale as a screening tool for shoulder impairment; (3) recommend a new PRO, or combination of PROs, that more accurately portrays the construct of shoulder dysfunction in the HNC population. Design: One hundred and eight-two individuals who had received a neck dissection procedure within the past 2 weeks to 18 months completed the PROs. Rasch methodologies were utilized to address the primary aim of the study through consideration of scale dimensionality [principal components analysis, item and person fit, differential item functioning (DIF)], scale hierarchy (gaps/redundancies, floor/ceiling effects, coverage of ability levels), response scale structure, and reliability (person and item reliability and separation statistics). The secondary aim was addressed through correlational analysis of the UW-QoL (shoulder subscale), DASH, QuickDASH, SPADI and NDII. Results: The DASH did not meet criteria for unidimensionality, and was deemed inappropriate for utilization in this sample. The QuickDASH, SPADI and NDII were all determined to be unidimensional. All scales had varying issues with person and item misfit, DIF, coverage of ability levels, gaps/redundancies, and optimal rating scale requirements. The NDII meets most requirements. All measures were found to meet thresholds for person and item separation and reliability statistics. The third aim of this study was not addressed because the NDII was determined to be appropriate for this population. Conclusions: Rasch analysis indicates the NDII is the most appropriate measure studied for this population. The QuickDASH and SPADI are recommended with reservation. The DASH and the UW-QoL (shoulder subscale) are not recommended.

Making complex medical decisions is becoming an increasingly challenging task due to the growing amount of available evidence to consider and the higher demand for personalized treatment and patient care. IT systems for the provision of clinical decision support (CDS) can provide sustainable relief if decisions are automatically evaluated and processed. In this paper, we propose an approach for quantifying similarity between new and previously recorded medical cases to enable significant knowledge transfer for reasoning tasks on a patient-level. Methodologically, 102 medical cases with oropharyngeal carcinoma were analyzed retrospectively. Based on independent disease characteristics, patient-specific data vectors including relevant information entities for primary and adjuvant treatment decisions were created. Utilizing the ϕK correlation coefficient as the methodological foundation of our approach, we were able to determine the predictive impact of each characteristic, thus enabling significant reduction of the feature space to allow for further analysis of the intra-variable distances between the respective feature states. The results revealed a significant feature-space reduction from initially 19 down to only 6 diagnostic variables (ϕK correlation coefficient ≥ 0.3, ϕK significance test ≥ 2.5) for the primary and 7 variables (from initially 14) for the adjuvant treatment setting. Further investigation on the resulting characteristics showed a non-linear behavior in relation to the corresponding distances on intra-variable level. Through the implementation of a 10-fold cross-validation procedure, we were further able to identify 8 (primary treatment) matching cases with an evaluation score of 1.0 and 9 (adjuvant treatment) matching cases with an evaluation score of 0.957 based on their shared treatment procedure as the endpoint for similarity definition. Based on those promising results, we conclude that our proposed method for using data-driven similarity measures for application in medical decision-making is able to offer valuable assistance for physicians. Furthermore, we consider our approach as universal in regard to other clinical use-cases, which would allow for an easy-to-implement adaptation for a range of further medical decision-making scenarios.

Indiana University-Purdue University Indianapolis (IUPUI)

Introduction: Frailty represents a complex geriatric syndrome associated with elevated rates of postoperative complications as shown for several malignant entities, including head and neck cancer. A specific screening instrument to assess frailty in head and neck patients does not exist. Both the FRAIL Scale and the G8 questionnaire are well-established and easy to use as screening tools. The present study’s aim was to assess the potential of frailty screening to predict postoperative complications in head and neck patients prior to surgery. Patients and methods: We recorded demographic data, pre-existing medical conditions and clinical characteristics in a prospective cohort of 104 head and neck cancer patients undergoing major head and neck surgery and assessed frailty prospectively on the day of admission utilizing the G8 questionnaire and the FRAIL Scale. We analyzed the link between occurrence of postoperative complications up to the twenty-first postoperative day and age, frailty and other covariates using χ 2 tests and receiver operating characteristic (ROC) curves. Results: There was no significant correlation between patients’ pre-existing medical conditions and postoperative complications. Whereas chronological age alone did not predict the occurrence of postoperative complications, frailty posed the highest risk for complications. Frailty according to either the G8 questionnaire or the FRAIL Scale predicted occurrence of complications with an area under the curve (AUC) of 0.64 (p = 0.018) and 0.62 (p = 0.039) and severe complications with an AUC of 0.72 (p = 0.014) and 0.69 (p=0.031), respectively. Neither frailty score correlated with age or with each other. Conclusion: Prospective screening using the FRAIL Scale or the G8 questionnaire reliably detected frailty in our sample group. Frailty is linked to increased risk of postoperative complications. The correct prediction of severe postoperative complications as shown identifies vulnerable cases and triggers awareness of potential complications. Anticipating risk allows for a more comprehensive view of the patient and triggers decision making towards risk adjustment, and therefore a selective view of alternative treatment modalities.

No description available.

Syfte: Att beskriva sjuksköterskors erfarenheter av att vårda patienter med huvud- och halscancer och alkoholmissbruk. Bakgrund: Cancer i huvud-halsområdet är den sjätte vanligaste dödsorsaken vid cancersjukdom. Överkonsumtion av alkohol tillsammans med rökning är de största enskilda riskfaktorerna för den här sjukdomen. Inom patientgruppen finns en stor representation av personer med ett risk- eller missbruk av alkohol, vilket ställer speciella krav på omvårdnadspersonalen. Design: Kvalitativ intervjustudie. Metod: Nio sjuksköterskor deltog i semistrukturerade intervjuer. Intervjuerna bandades och transkriberades sedan ordagrant innan de analyserades med tematisk-narrativ metod. Resultat: Sjuksköterskornas erfarenheter fångades i tre huvudteman: en mångfacetterad sjuksköterskeuppgift, den komplexa patienten och missbrukets påverkan på patienten. En mångfacetterad sjuksköterskeuppgift består av många delar. Den största delen bestod av berättelser om förhållningssätt och interaktion med patienter, behovet av kompetens hos sjuksköterskorna och svårigheter kring att motivera patienten, en annan handlar om bristen på samarbete med andra kliniker. Även kontakt med anhöriga berörs.Kring den komplexa patienten handlade det om känslor, nutritionsproblem, smärta och att de sågs som utmanande människor. Missbrukets påverkan på patienten bestod av patienternas kamp att hålla sig nyktra under behandlingsperioden, likväl som de anpassningar som sjuksköterskorna blev tvungna att göra i omvårdnaden av dem. Slutsats: Denna studie visade att det fanns ett behov av ökad kompetens hos sjuksköterskor och ett bättre samarbete mellan kliniker. Verktyg för att tala med patienter kring deras missbruk och vikten av en god relation betonas. Slutligen pekades på behovet av ytterligare forskning för att förbättra omvårdnaden av huvud-halscancerpatienter med alkoholmissbruk.