O câncer de pulmão é uma doença maligna que acomete principalmente a população de adultos e idosos na faixa etária dos 40 aos 80 anos. Sua principal causa continua sendo o tabagismo, e sua sobrevida varia com o estadiamento da doença no momento do diagnóstico e sua alta taxa de mortalidade está associada ao diagnóstico tardio da doença, o que limita as opções de tratamento curativo. A Qualidade de Vida Relacionada à Saúde (QVRS) de sujeitos com câncer de pulmão é influenciada por múltiplos fatores, incluindo sintomas, capacidade funcional, estratégias de enfrentamento e rede social de suporte, dentre outros. Entretanto, ainda falta esclarecer o impacto da fadiga na QVRS de pessoas com câncer de pulmão avançado. O objetivo deste estudo é avaliar a QVRS e a fadiga de sujeitos com diagnóstico de câncer de pulmão em cuidados paliativos e identificar a relação entre a presença de fadiga e percepção da QVRS desta população. Trata-se de um estudo transversal e com abordagem quantitativa, correlacional, com uma casuística composta por 120 sujeitos, sendo 60 com câncer de pulmão em cuidados paliativos (grupo de estudo) e 60 sem diagnóstico oncológico (grupo controle). Durante a coleta de dados foram aplicadas as escalas: Karnofsky Performance Scale (KPS), o Critério de Classificação Econômica Brasil (CCEB - versão 2014), a Escala de Fadiga de Piper - revisada e a European Organization for Research in the Treatment of Cancer Questionnaire-core 30 (EORTC- QLQ-C30), com seu módulo específico para câncer de pulmão - o Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13). Para a análise dos resultados foi realizada estatística descritiva (Mediana, Mínimo e Máximo e 1º e 3º quartil) e testes não paramétricos de Mann-Whitney e Kruskal-Wallis para a comparação entre os grupos e variáveis. Os resultados indicaram que houve significância estatística na comparação entre os grupos para as escalas funcionais, de sintomas e dificuldades financeiras do EORTC QLQ-C30 e para os sintomas associados ao câncer e/ou decorrentes do seu tratamento avaliados pelo módulo QLQ-LC13, bem como para a presença de fadiga. A fadiga foi identificada como o sintoma mais frequente nessa população, relacionada com capacidade funcional reduzida (avaliada pelo KPS) e pior percepção da QVRS. Portanto, sujeitos com diagnóstico de câncer de pulmão em cuidados paliativos apresentam maior carga do sintoma fadiga em comparação com a população em geral e quanto maior a fadiga e de outros sintomas, maior o comprometimento da QVRS dos sujeitos com câncer de pulmão em cuidados paliativos. Este estudo traz contribuições relevantes à Saúde Pública por meio da investigação da relação entre doenças crônicas oncológicas e qualidade de vida relacionada à saúde, para o tratamento sujeitos com câncer de pulmão em cuidados paliativos e que apresentam a fadiga como fator limitante para a realização de suas atividades diárias bem como para os diversos profissionais que atuam na atenção à pessoa com uma condição oncológica em cuidados paliativos / Lung cancer is a malignant disease that mostly affects adults aged between 40 to 80 years old. The main cause of lung cancer is smoking and the survival varies according with the disease stage at the moment of the diagnosis and the high lung cancer mortality rate is related to a late diagnosis, which limits the curative treatment options.. Health Related Quality of Life (HRQoL) of people who have lung cancer is influenced by multiple factors including symptoms, functional capacity, coping strategies and social support networking, among others. However, there is still a need for clarify the impact of fatigue on HRQoL of people with advanced lung cancer. The purpose of this study was to evaluate HRQoL and fatigue of subjects diagnosed with lung cancer in palliative care and identify the relationship between the presence of fatigue and perception of hrqol in this population. this is a cross-sectional, quantitative and correlational approach in which sample was composed of 120 subjects, 60 of them with lung cancer in palliative care (study group) and the others 60 without cancer diagnosis (control group). During data collection were applied the scales: Karnofsky Performance Scale (KPS), Brazil Criterion of Economic Classification (CCEB - version 2014), the Piper Fatigue Scale - Revised and the European Organization for Research in the Treatment of Cancer Questionnaire-Core 30 (EORTC-QLQ-C30), with its specific module for lung cancer - the Quality of Life Questionnaire lung Cancer 13 (QLQ-LC13). For data analysis it was performed descriptive statistics (median, Minimum and Maximum and 1st and 3rd quartile) and two non-parametric statistical tests -- Mann Whitney and Kruskal-Wallis. for comparison between groups and variables. The results indicated significant statistical differences when comparing the groups for the functional and symptoms scales, for the financial difficulties of EORTC QLQ-C30 and symptoms related to and/or resulting from lung cancer and its treatment evaluated by QLQ-LC13 module and for fatigue presence. Fatigue was identified as the most frequent symptom in this population, it\'s related to reduced functional capacity (assessed by KPS) and worse perception of HRQoL. Therefore, subjects diagnosed with lung cancer in palliative care have a higher burden of fatigue compared to general population and the greater fatigue and other symptoms, the greater HRQOL impairment of lung cancer patients in palliative care. This study provides important contributions to public health by investigating the relationship between chronic diseases and oncology HRQoL, to treatment of lung cancer people in palliative care who have fatigue as a limiting factor to carrying on their daily activities and to health professionals who works with oncologic palliative care

Introdução: O câncer de pulmão é um dos tipos mais comuns de câncer, sendo ele responsável pelo maior número de mortes por neoplasias no mundo. Pacientes com câncer de pulmão apresentam alta prevalência de desnutrição, que está relacionada com piora do prognóstico. A desnutrição ocorre em 60% dos pacientes no momento do diagnóstico, levando a um mau prognóstico, independente do estágio do tumor. Avaliação nutricional de pacientes com câncer deve ser realizada à luz de qualquer proposta terapêutica, ainda que esta seja paliativa. Neste sentido, o método validado de Avaliação Subjetiva Global Produzida pelo Próprio Paciente (ASG-PPP) e adaptado por Ottery et al para pacientes oncológicos a partir da Avaliação Subjetiva Global, ajuda a identificar precocemente os pacientes que estão em risco nutricional. A nutrição é fundamental nestes pacientes em doença avançada, pois fornece a quantidade adequada de nutrientes, tem um importante papel psicológico, social, espiritual e cultural, além de ajudar a manter um sentido de autonomia e bem-estar. Objetivo: Relacionar a Capacidade Funcional através do índice de Karnofsky e o estado nutricional, sinais e sintomas avaliados pelo método subjetivo (ASG-PPP), com a sobrevida de pacientes com neoplasia pulmonar mestastática. Pacientes e métodos: Trata-se de um estudo transversal, constituído por 51 pacientes, ambos os sexos, portadores de neoplasia pulmonar com doença metastática em estadiamento IIIb e IV, atendidos em nível ambulatorial e hospitalar no Hospital Santa Rita, Complexo Hospitalar Santa Casa de Porto Alegre. A sobrevida dos pacientes foi verificada ao final do estudo, através de revisão de prontuários e contato telefônico com o responsável pelo paciente. Resultados: Os pacientes apresentaram-se com idade 61,84±10,83 anos (40 a 82 anos); 34 (66,7%) eram gênero masculino e 17 (33,3%) do feminino. A mediana do tempo de sobrevida foi de 186 dias (IC 95%: 158,8; 213,2). Os pacientes internados tiveram sobrevida significativamente inferior (mediana=145 dias (IC 95%=135 - 155) aos que foram atendidos ambulatorialmente (mediana=221 dias (IC 95%=199 - 243). Os pacientes em estágio IV tiveram sobrevida significativamente inferior (mediana=176 dias; IC 95%=127 - 225) àqueles em estágio IIIb (mediana=221; IC 95%=147 - 295). Os pacientes com metástase hepática tiveram sobrevida significativamente inferior (mediana=115 dias; IC 95%=74 - 155) aos sem metástase hepática (mediana=199; IC 95%=174 - 224). Os pacientes com metástase pleural apresentaram sobrevida significativamente superior (mediana=386 dias; IC 95%=129 - 643) aos sem metástase pleural (mediana=174; IC 95%=133 - 214). Não houve diferença estatisticamente significativa entre as curvas de sobrevida dos diferentes estágios nutricionais (teste de log rank; p=0,651). Os acamados tiveram sobrevida significativamente inferior (mediana=115 dias; IC 95%=87 - 143) que os com capacidade física normal (mediana=255 dias; IC 95%=202 - 308). Quanto maior a depleção corporal total, pior a sobrevida do paciente (p=0,014). O aumento de 1 ponto neste item da ASG-PPP (RDI=1,70; IC 95%=1,12 – 2,59) pode aumentar o risco de óbito, em média 70%. O índice de Karnofsky também se associou significativamente com a sobrevida (p=0,016), sendo que para um aumento de 10% na escala de nível de desempenho, o risco de óbito diminuiu em 23% (RDI=0,77; IC 95%=0,76 – 0,79). Os sintomas mais prevalentes que afetaram a alimentação entre os pacientes foram a falta de apetite (66,7%), depressão (51%) e dor (39,2%) e os menos relatados foram dor na boca e vômitos (5,9%). Os fatores que permaneceram associados estatisticamente com o óbito após o ajuste pela análise multivariada de Regressão de Cox foram metástase hepática e internação hospitalar como fatores de risco para óbito e metástase pleural e melhor índice de Karnofsky como fatores protetores. Conclusão: A sobrevida dos pacientes eutróficos foi levemente superior a dos pacientes em risco nutricional e a dos severamente desnutridos. Quanto maior a depleção corporal total e pior o índice de Karnofsky maior o risco de óbito. Não foi encontrada uma associação estatisticamente significativa entre os valores de Hemograma, Albumina Sérica e Contagem Total de Linfócitos (CTL) com o estado nutricional da população em estudo e a sobrevida. / Introduction: Lung cancer is one of the most common cancers in the world, and it is today the most lethal of the neoplastic diseases. Patients with lung cancer show high prevalence of malnutrition, the latter being related to worsening of the prognosis. Malnutrition occurs in 60% of the patients at the moment of diagnosis, leading to a bad prognosis, regardless of the tumor stage. Nutritional evaluation of patients with cancer should be conducted in the light of a therapeutic proposal, even if it’s palliative. In this way, the validated method Scored Patient-Generated Subjective Global Assessment (PG-SGA), adapted by Ottery et al for oncologic patients from the questionnaire of Subjective Global Assessment, helps to precociously identify patients that are in nutritional risk. Nutrition is fundamental in these patients with advanced disease for it supplies the adequate amount of nutrients, performs an important psychological, spiritual and cultural role, besides helping to build a sense of autonomy and well-being. Objective: to relate Functional Capacity through the Karnofsky Index and the nutritional state, signs and symptoms evaluated by the subjective method (PG-SGA), to the survival of patients with metastatic pulmonary neoplasia. Patients and methods: It’s a transversal study, constituted by 51 patients, both genders, carriers of pulmonary neoplasia with metastatic disease on stages IIIb and IV, both in and outpatients at Santa Rita Hospital, Complexo Hospitalar Santa Casa de Porto Alegre. The survival of the patients in the study was assessed at the end of the study, through review of the chart and phone contact with the patient’s keeper. Results: The average age is 61.84 (± 10.83 varying between 40 and 82), being 34 (66.7%) male and 17 (33.3%) female. The median of survival is 186 days (CI 95%; 158.8; 213.2). The inpatients have a significantly inferior survival (median=145 days; CI 95%=135 – 155) than the outpatients (median=221 days; CI 95%=199 – 243). Patients on stage IV have a significantly inferior survival (median=176 days; CI 95%=127 - 225) than patients on stage IIIb (median=221; CI 95%= 147 - 295). Patients with hepatic metastasis have a significantly inferior survival (median=115 days; CI 95%=74 - 155) than patients without hepatic metastasis (median=199 days; CI 95%=174 - 224). Patients with pleural metastasis have a significantly superior survival (median=386 days; CI 95%=129 – 643) than patients without pleural metastasis (median=174; CI 95%=133 – 214). There was no meaningful statistical difference between survival curves of different nutritional stages (log rank test; p=0,652). Bedridden patients have a significantly inferior survival (median=115 days; CI 95%=87 – 143) than patients with normal physical capacity (median=255 days; CI 95%=202 – 308). The higher the total body depletion, the lower the patient survival (p=0.014). The increase of 1 point in this item of the PG-SGA (IDR=1.70; CI 95%=1.12 – 2.59) may increase risk of death, averagely, by 70%. Karnofsky index was also significantly associated with survival (p=0.016), seeing that for an increase of 10% in the performance scale the risk of death decreased in 23% (IDR=0.77; CI 95%=0.76 – 0.79). The most prevalent symptoms that affect nourishment among the patients were lack of appetite (66.7%), depression (51%) and pain (39.2%) and the least mentioned were mouth pain and vomit (5.9%). Factors that remain statistically associated with death after the adjust by the multivariate analysis by regression of Cox were hepatic metastasis and hospital internment as risk factors for death, and pleural metastasis and better Karnofsky index as protective factors. Conclusion: The survival of eutrophic patients was mildly superior to that of patients in nutritional risk and to that of severely malnourished patients. The higher the total body depletion and the worse the Karnofsky index, the higher the risk of death. No significant statistical association was found between Hemogram, Serum Albumin, and Total Lymphocyte Count (TLC) with the nutritional status of the population in study and survival.

Purpose: To examine the association of affective experience and health-related quality of life in lung cancer patients, we hypothesized that negative affect would be positively, and positive affect would be negatively, associated with perceived health. Methods: A sample of 133 English-speaking lung cancer patients (33% female; mean age = 63.68 years old, SD = 9.37) completed a battery of self-report surveys. Results: Results of our secondary analysis indicate that trait negative affect was significantly associated with poor physical and social functioning, greater role limitations due to emotional problems, greater bodily pain, and poor general health. Positive affect was significantly associated with adaptive social functioning, fewer emotion-based role limitations, and less severe bodily pain. In a full model, positive affect was significantly associated with greater levels of social functioning and general health, over and above the effects of negative affect. Conclusions: Reduction of negative affect is an important therapeutic goal, but the ability to maintain positive affect may result in greater perceived health. Indeed, engagement in behaviors that result in greater state positive affect may, over time, result in dispositional changes and enhancement of quality of life.

Pharmacological ascorbate, intravenous administration of high-dose vitamin C aimed at peak plasma concentrations ~ 20 mM, has recently re-emerged, after a controversial history, as a potential anti-cancer agent in combination with standard-of-care radiation and chemotherapy-based regimens. The anti-cancer effects of ascorbate are hypothesized to involve the auto-oxidation or metal-catalyzed oxidation of ascorbate to generate H2O2, and preclinical in vitro and in vivo studies in a variety of disease sites demonstrate the efficacy of adjuvant ascorbate. Furthermore, phase I clinical trials in pancreatic and ovarian cancer have demonstrated safety and tolerability in combination with chemotherapy and preliminary results suggest therapeutic efficacy. Both preclinical in vitro and in vivo studies as well as phase I clinical trials suggest a cell-intrinsic mechanism of selective toxicity of cancer cells as compared to normal cells; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study aims to investigate the preclinical therapeutic efficacy of pharmacological ascorbate in combination with standard cancer therapies in three novel disease sites: non-small cell lung cancer (NSCLC), glioblastoma multiforme (GBM), and some histological subtypes of sarcoma. In vitro experiments demonstrate cancer cell-selective susceptibility to pharmacological ascorbate as compared to normal cells of identical cell lineages. Furthermore, in vivo murine xenograft models of NSCLC, GBM, and fibrosarcoma demonstrate therapeutic efficacy of pharmacological ascorbate in combination with chemotherapy and/or radiation as compared to chemotherapy and/or radiation alone without any additional therapeutic toxicity. Additionally, a phase I clinical trial in GBM subjects demonstrates the safety and tolerability of ascorbate in combination with radiation and temozolomide therapy. Although not powered for efficacy, preliminary results suggest that ascorbate may be efficacious in these subjects (median survival 18.2 months vs. 14.6 months in historical controls), and, importantly, that ascorbate therapy may be independent of MGMT promoter methylation status (median survival 23.0 months vs. 12.7 months in historical controls with absent MGMT promoter methylation). Preliminary results from a phase II clinical trial of ascorbate in combination with carboplatin/paclitaxel chemotherapy in advanced stage NSCLC subjects also demonstrate promising preliminary results related to efficacy (objective response rate (ORR) 29% and disease control rate (DCR) 93% vs. historical control ORR 15-19% and DCR 40%). In addition to demonstrating the potential efficacy of pharmacological ascorbate in combination with standard anti-cancer therapies, this work demonstrates that the selective toxicity of ascorbate may be mediated by perturbations in cancer cell oxidative metabolism. Increased mitochondrial-derived O2- and H2O2 disrupts cellular iron metabolism, resulting in increased iron uptake via Transferrin Receptor and a larger intracellular labile iron pool. The larger pool of labile iron in cancer cells underlies the selective sensitivity of cancer cells to ascorbate toxicity through pro-oxidant chemistry with ascorbate-produced H2O2. This mechanism is further supported by the finding of increased levels of O2- and labile iron in patient lobectomy-derived NSCLC tissue as compared to adjacent normal fresh frozen tissue. Together, these studies demonstrate the feasibility, selective toxicity, tolerability, and potential efficacy of pharmacological ascorbate in NSCLC, GBM, and sarcoma therapy and propose that further investigations of tumor and systemic iron metabolism are required to determine if these alterations can be exploited to enhance therapeutic efficacy or serve as therapeutic biomarkers.

Lung cancer is the leading cause of cancer death in the United States. While low-dose computed tomography (CT) screening reduces lung cancer mortality by 20%, 97% of suspicious lesions are found to be benign upon further investigation. Computer-aided diagnosis (CAD) tools can improve the accuracy of CT screening, however, current CAD tools which focus on imaging characteristics of the nodule alone are challenged by the limited data captured in small, early identified nodules. We hypothesize a CAD tool that incorporates quantitative CT features from the surrounding lung parenchyma will improve the ability of a CAD tool to determine the malignancy of a pulmonary nodule over a CAD tool that relies solely on nodule features. Using a higher resolution research cohort and a retrospective clinical cohort, two CAD tools were developed with different intentions. The research-driven CAD tool incorporated nodule, surrounding parenchyma, and global lung measurements. Performance was improved with the inclusion of parenchyma and global features to 95.6%, compared to 90.2% when only nodule features were used. The clinically-oriented CAD tool incorporated nodule and parenchyma features and clinical risk factors and identified several features robust to CT variability, resulting in an accuracy of 71%. This study supports our hypothesis that the inclusion of parenchymal features in the developed CAD tools resulted in improved performance compared to the CAD tool constructed solely with nodule features. Additionally, we identified the optimal amount of lung parenchyma for feature extraction and explored the potential of the CAD tools in a clinical setting.

Hexavalent chromium, Cr(VI), is an established human carcinogen that is a worldwide environmental health concern. It is well understood that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to Cr(VI)-induced carcinogenesis. After decades of research some cancer hallmarks remain understudied for the mechanism of Cr(VI) carcinogenesis. Dysregulated cellular energetics have been established as a hallmark of cancer. Energy pathways that become dysregulated in cancer include mitochondrial respiration, lipogenesis, pentose phosphate pathway, one carbon metabolism, and increased anaerobic glycolysis in the presence of oxygen or ‘Warburg effect’. To investigate metabolism changes in Cr(VI) carcinogenesis, we exposed human lung epithelial cells (BEAS-2B cells) to Cr(VI) for six months and isolated a colony from soft agar. To confirm the results in the BEAS-2B cells, we used two other sets of Cr(VI)-transformed cells, human lung epithelial cells (BEP2D cells) and human lung fibroblasts (WTHBF-6 cells). We found increased lipogenesis related protein expressions including: ATP citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) in Cr(VI)-transformed cells as compared to passage-matched control cells. We also observed increased palmitic acid levels, confirming that Cr(VI)-transformed cells were making more lipids. Cr(VI)-transformed BEAS-2B cells had decreased colony formation in soft agar and decreased cell growth when treated with a FASN inhibitor (C75). ACLY, ACC1, and FASN protein expressions were also increased in chromate-induced lung tumors in human tissue samples. We also observed that Cr(VI)-transformed human lung cells (BEAS-2B, BEP2D, and WTHBF-6 cells) had no major changes in their mitochondrial respiration as measured by the Seahorse Analyzer when compared to their passage-matched control cells. Conversely, xenograft tumor-derived cells had mitochondrial respiratory dysfunction. Interestingly, we also found that Cr(VI)-transformed human lung cells (BEAS-2B, BEP2D, and WTHBF-6 cells) had no major changes in their glycolytic function as measured by the Seahorse Analyzer when compared to their passage-matched control cells. Similarly, these cells did not have changes in glycolytic enzymes or extracellular L-lactate levels. Moreover, xenograft tumor-derived cells showed no changes in glycolytic endpoints or L-lactate levels. This indicates these cells did not undergo the ‘Warburg effect’. These data demonstrate that increased lipogenesis is important to Cr(VI)-induced lung carcinogenesis and are consistent with the cancer literature which reports that increased lipogenesis proteins occur during carcinogenesis. Additionally, our results indicate mitochondrial respiratory dysfunction is likely a result of the tumor microenvironment and a later step during Cr(VI) carcinogenesis. Lastly, we observed the ‘Warburg effect’ is not required for Cr(VI)-induced carcinogenesis in vitro. However, it remains to be shown if the ‘Warburg effect’ is still a consequence or contributing factor for tumorigenesis. Future studies are needed to investigate other metabolic pathways in Cr(VI)-induced carcinogenesis. In conclusion, some metabolism pathways are important to Cr(VI)-induced carcinogenesis, while others appear not to be.

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) is known to play a role in the metastasis and poor prognosis of cancer, and is induced by extracellular matrix (ECM) stiffness. Hallmarks of EMT include loss of E-Cadherin and increase in Vimentin. This research investigates the role of KRAS in EMT transition due to increased ECM stiffness in KRAS mutant NSCLC, and how this affects the efficacy of KRAS and MEK inhibition. To understand how KRAS mutations in NSCLC play a role in this stiffness induced EMT, experiments were performed to detect the gene and protein expression of EMT markers, as well as possible sources of mechanosensing, including primary cilia and receptor tyrosine kinases. We hypothesized that KRAS plays a role in activation of mechanosensors and directly correlates to EMT induced by increased mechanical forces. Results show when KRAS was inhibited and there was increased mechanical forces, either from stretch or substrate stiffness, there was a decreased activation of mechanosensors. KRAS inhibition also prevented the cells from undergoing stiffness-induced EMT. This supports our hypothesis that KRAS plays a key role in ECM stiffness induced EMT. Future studies include examining the mechanism behind this phenomenon and in vivo studies.

The objectives of the work The objective of this work has been set as the mapping of degree of patient's contentment/ rate of patient's satisfaction in view of the nurse's approach within the scope of the post-thoracic operation care and the evaluation/ assessment whether the needs of the aforementioned patients have been satisfied. Another objective of the research enquiry has been set as finding out the level of the nurse's awareness regarding the ways and possibilities of the subsequent care. Methodology For the purpose of the research enquiry the form of qualitative research has been chosen and adopted, which has been applied and performed by means of using a method of interviewing i.e. putting questions which have been prepared beforehand, well in advance. Research array of patients consisted of 10 patients from one hospital (which is not going to be specified in this work) as well as 8 nurses whose job was to take care of the post-operative patients/ the post-thoracic operation patients. The results of the research have been processed by applying the method of open coding, pencil-paper method. Assets and Benefits of this Work The research enquiry has showed certain level of absence of desirable knowledge as well as ignorance of the staff taking care of the patients regarding the ways of subsequent care. Nurses should be educated about the possibilities of home care, hospice care as an integral part of their profession. The results gained by research enquiry process could be presented at seminars, conferences aimed at the subsequent care.

Seit Beginn der 90er Jahre wurden minimal-invasive Operationsmethoden zur Therapie des Bronchialkarzinoms eingeführt, ohne vorher sicherzustellen, daß sie hinsichtlich der onkologischen Sicherheit und Radikalität der konventionellen Operationsmethode ebenbürtig sind. Die vorliegende Arbeit hat daher die Entwicklung einer onkologisch adäquaten thorakoskopischen Lobektomie zur Aufgabe. Die dazu notwendige wissenschaftliche Evaluation erfolgt in mehreren Schritten. Zunächst wird der aktuelle operative Standard der konventionellen Chirurgie beim Bronchialkarzinom in der Literatur dargestellt. Auf dieser Grundlage wird die thorakoskopische Resektion inklusive Lymphadenektomie beim Bronchialkarzinom definiert. Dieser Standard dient als Vorlage für die Entwicklung der minimal-invasiven Chirurgie im Tier- und Leichenmodell. Im ersten Schritt der Phase I wird anhand tierexperimenteller Arbeiten untersucht, ob und unter welchen technischen Voraussetzungen eine thorakoskopische Lobektomie vollständig minimal-invasiv durchführbar ist. Mit den anschließenden chirurgisch-anatomischen Untersuchungen soll festgestellt werden, inwieweit die erarbeitete thorakoskopische Technik den onkologischen Prinzipien, insbesondere der Lymphadenektomie, Rechnung trägt. Diese Phase stellt die Grundvoraussetzung für eine weitere Evaluierung der erarbeiteten Ergebnisse in der Phase II dar. Die Erprobung der erarbeiteten Technik in der Klinik dient der Überprüfung auf Morbidität und Mortalität im Vergleich zur konventionellen Operationsmethode und der Übertragung in randomisierte Studien zum Nachweis relevanter Unterschiede im Frühverlauf (Phase IIIa) und Spätverlauf (Phase IIIb). / Since the beginning of the 1990's, minimal invasive surgery has expanded to include extensive thoracic operations, especially the lobectomy. Implementation of this procedure has been described in numerous publications, however the development occurred unsystematically. So the oncologic radicality and safety of both thoracoscopic lobectomy and lymph node dissection is a debated topic in the literature. Therefore, previous results could not prove that minimal invasive resections by bronchial carcinoma are equivalent to conventional surgical methods with respect to oncological security and radical resectability. For this reason thoracoscopic lobectomy with lymphadenectomy is investigated for radicality and completeness according to the recommendations for scientific evaluation. In a first step the criterias of an oncologic lung resection - lobectomy and lymphadenectomy - are established. This definition is the basis for the following phase I, the animal study and the experimental-anatomic study in a human cadaver model. The task of the animal study is to examine if a lobectomy could be done by thoracoscopic technique completely and on which conditions. Than an experimental-anatomic study in a cadaver model is done to control the extent of the radical thoracoscopic lobectomy with lymphadenectomy by a following thoracotomy. This study is essential for a phase II-trial, the application of the acquired thoracoscopic technique in a pilot study for examination of morbidity and mortality. The comparison of the thoracoscopic and the conventional lobectomy in the pilot study also served to evaluate potential advantages of the minimal-invasive method. These advantages are a strong argument in favour of the introduction of the thoracoscopic method in to the clinic for prospective-randomized trials (phase III a and III B).

<p>In Sweden approximately 2800 new lung cancer patients are diagnosed every year. Radiotherapy is used with curative intention in certain groups of patients. The aim of this thesis is to study the basis of differences in radioresistance and the possibility to predict response to radiotherapy.</p><p>In the first study we investigated, using the comet assay, four lung cancer cell lines with different sensitivity towards radiation. A clear dose-response relationship for radiation-induced DNA single strand and double strand breaks were found. All cell lines showed a remarkably efficient repair of both the DNA single strand and double strand breaks one hour after irradiation. However, further studies in one radioresistant and one radiosensitive cell line demonstrated that repair during the first 15 min had the best accordance with radiosensitivity measured as surviving fraction.</p><p>In the second and third study, sequencing studies of the p53 gene were performed on cell lines as well as on tumour material. Cell lines that were expressing a mutation in exon 7 were associated with increased radiosensitivity compared with tumor cell lines with mutations in other exons. In the clinical study, 10 patients were found to be mutated in the p53 gene whereas the other 10 patients were not. No correlation to clinical parameters could be drawn.</p><p>In the fourth study, serum from 67 patients with a confirmed diagnosis of non-small cell lung cancer was investigated for the presence of p53 antibodies. P53 antibodies in sera, taken prior to radiation treatment, were associated with increased survival.</p><p>The summary of this thesis indicates that the p53 gene has an impact on the effect of radiotherapy in lung cancer. The presence of p53 antibodies might be of clinical interest for predicting survival after radiotherapy. Further studies on the importance of the p53 gene on early repair are of interest. </p>