Systems Modeling of Lung Cancer Screening Programs to Improve Quality

Thesis (Master's)--University of Washington, 2016-08

Childhood Non-Langerhans Cell Histiocytosis – An Atypical Case

Introduction: Histiocytoses correspond to a heterogeneous group of disorders characterized by the proliferation andinfiltration of histiocytes in tissues. For years, many of the histiocytoses where known by numerous names, reflecting the lack of understanding regarding their origin. Case report: A previously healthy, 4-month-old infant presented a cutaneous lesion of progressive growth on his nose since 1 month ago. The mother has a diagnosis of Sjögren syndrome. On examination, there was a firm well-defined erythematous plaque with 30 mm of diameter and raised edges, on the bridge of the nose. At the left cheek, left thoracic region and right arm there were also small erythematous papules with 5 days of evolution. The analytical study showed elevated antinuclear antibodies and anti-SS-A. Histopathological examination confirmed the diagnosis of non-Langerhans cells histiocytosis. Progressively, more annular erythematous papules and plaques appeared scattered over the face, trunk and limbs with spontaneous resolution of the first lesion on the nose. About 2 months after the initial evaluation, all lesions had regressed spontaneously, with normalization of analytical study at one year-old. Conclusion: Many authors believe that the different subtypes of histiocytosis represent only different stages of the same disease. Immunophenotyping of histiocytosis does not always identify the subtype involved, making the occurrence of atypical cases frequent.

Exposure to Stressful Life Events and Lung Cancer Risk

Objectif: Examiner l’association entre l'exposition aux évènements stressants de la vie et le cancer du poumon. Méthodes: Les données proviennent d’une étude cas-témoins, menée chez les hommes et les femmes vivant dans la région métropolitaine de Montréal entre 1996 et 2001. Le cancer du poumon d’un cas éligible devait être confirmé histologiquement à l’un des 18 hôpitaux de cette région. Les témoins ont été sélectionnés aléatoirement de la liste électorale du Québec et ont été appariés au cas par fréquence de groupes d'âge et par sexe. Un questionnaire a été administré en entrevue pour recueillir les données, dont l’évaluation de huit évènements stressants de la vie par le participant. Si le participant avait vécu un évènement stressant ciblé durant les six dernières années, il devait aussi coter cet évènement sur une échelle de trois points. La régression logistique non conditionnelle a été utilisée pour estimer les rapports de cotes ainsi que leurs intervalles de confiance à 95%. Des analyses par sexe, niveau de tabagisme et par type histologique ont été réalisées. Nous avons aussi analysé l’association entre le cancer du poumon et le nombre total d'évènements, les évènements de perte et les évènements socioéconomiques, ainsi que chaque évènement individuellement. Les analyses des scores d'impact autoévalués et avec un score externe de perception, ont également été menées. Résultats: La population de ce projet comprend 1061 cas et 1422 témoins, âgés de 35 à 70 ans. Les participants inclus avaient répondu aux sections du questionnaire portant sur les facteurs de style de vie et sur l'historique de tabagisme. Dans l'ensemble, nous n’avons pas observé d’association entre le cancer du poumon et l'exposition aux évènements stressants de la vie. Nous avons observé une diminution du risque pour les évènements socioéconomiques autoévalués comme peu stressants (RC=0,50; IC 95%= 0,31 - 0,81). Conclusion: Nos résultats suggèrent que les évènements socioéconomiques sont associées à un risque réduit si ces évènements sont considérés comme peu stressant.

Exposure to Stressful Life Events and Lung Cancer Risk

Objectif: Examiner l’association entre l'exposition aux évènements stressants de la vie et le cancer du poumon. Méthodes: Les données proviennent d’une étude cas-témoins, menée chez les hommes et les femmes vivant dans la région métropolitaine de Montréal entre 1996 et 2001. Le cancer du poumon d’un cas éligible devait être confirmé histologiquement à l’un des 18 hôpitaux de cette région. Les témoins ont été sélectionnés aléatoirement de la liste électorale du Québec et ont été appariés au cas par fréquence de groupes d'âge et par sexe. Un questionnaire a été administré en entrevue pour recueillir les données, dont l’évaluation de huit évènements stressants de la vie par le participant. Si le participant avait vécu un évènement stressant ciblé durant les six dernières années, il devait aussi coter cet évènement sur une échelle de trois points. La régression logistique non conditionnelle a été utilisée pour estimer les rapports de cotes ainsi que leurs intervalles de confiance à 95%. Des analyses par sexe, niveau de tabagisme et par type histologique ont été réalisées. Nous avons aussi analysé l’association entre le cancer du poumon et le nombre total d'évènements, les évènements de perte et les évènements socioéconomiques, ainsi que chaque évènement individuellement. Les analyses des scores d'impact autoévalués et avec un score externe de perception, ont également été menées. Résultats: La population de ce projet comprend 1061 cas et 1422 témoins, âgés de 35 à 70 ans. Les participants inclus avaient répondu aux sections du questionnaire portant sur les facteurs de style de vie et sur l'historique de tabagisme. Dans l'ensemble, nous n’avons pas observé d’association entre le cancer du poumon et l'exposition aux évènements stressants de la vie. Nous avons observé une diminution du risque pour les évènements socioéconomiques autoévalués comme peu stressants (RC=0,50; IC 95%= 0,31 - 0,81). Conclusion: Nos résultats suggèrent que les évènements socioéconomiques sont associées à un risque réduit si ces évènements sont considérés comme peu stressant.

Surgical management of lung cancer in Western Australia in 1996 and its outcomes

Background: All cases of lung cancer diagnosed in Western Australia in 1996 in which surgery was the primary treatment, were reviewed. Reported herein are the characteristics of the patients, the treatment outcomes and a comparison of the management undertaken with that recommended by international guidelines. Methods: All patients with a new diagnosis of lung cancer in Western Australia in the calendar year of 1996 were identified using two different population-based registration systems: the Western Australian (WA) Cancer Registry and the WA Hospital Morbidity Data System. A structured questionnaire on the diagnosis and management was completed for each case. Date of death was determined through the WA Cancer Registry. Results: Six hundred and sixty-eight patients with lung cancer were identified; 132 (20%) were treated with surgery. Lobectomy was the most frequently performed procedure (71%), followed by pneumonectomy (19%). Major complications affected 23% of patients. Postoperative mortality was 6% (3% lobectomy, 12% pneumonectomy). At 5 years the absolute survival was as follows for stage I, II, IIIA, IIIB, respectively: 51%, 45%, 12%, 5%. Conclusions: Investigations and choice of surgery in WA in 1996 reflect current international guidelines. The survival of patients with resectable lung cancer remains unsatisfactory.

Cochrane systematic reviews of treatments for lung cancer

Morbidity and mortality from lung cancer is a major burden to global health. The integration of expert clinical experience, patient preference and high-quality evidence, including Cochrane systematic reviews, can only help improve outcomes from this highly lethal condition.

Processing of mutated human proinsulin to mature insulin in the non-endocrine cell line, CHO

Heterologous genes encoding proproteins, including proinsulin, generally produce mature protein when expressed in endocrine cells while unprocessed or partially processed protein is produced in non-endocrine cells. Proproteins, which are normally processed in the regulated pathway restricted to endocrine cells, do not always contain the recognition sequence for cleavage by furin, the endoprotease specific to the constitutive pathway, the principal protein processing pathway in non-endocrine cells. Human proinsulin consists of B-Chain-C-peptide-A-Chain and cleavage at the B/C and C/A junctions is required for processing. The B/C, but not the C/A junction, is recognised and cleaved in the constitutive pathway. We expressed a human proinsulin and a mutated proinsulin gene with an engineered furin recognition sequence at the C/A junction and compared the processing efficiency of the mutant and native proinsulin in Chinese Hamster Ovary cells. The processing efficiency of the mutant proinsulin was 56% relative to 0.7% for native proinsulin. However, despite similar levels of mRNA being expressed in both cell lines, the absolute levels of immunoreactive insulin, normalized against mRNA levels, were 18-fold lower in the mutant proinsulin-expressing cells. As a result, there was only a marginal increase in absolute levels of insulin produced by these cells. This unexpected finding may result from preferential degradation of insulin in non-endocrine cells which lack the protection offered by the secretory granules found in endocrine cells.

18F-FDG measurement in primary lung cancer: SUV normalization to different distribution volumes

Introduction: Standard Uptake Value (SUV) is a measurement of the uptake in a tumour normalized on the basis of a distribution volume and is used to quantify 18F-Fluorodeoxiglucose (FDG) uptake in tumors, such as primary lung tumor. Several sources of error can affect its accuracy. Normalization can be based on body weight, body surface area (BSA) and lean body mass (LBM). The aim of this study is to compare the influence of 3 normalization volumes in the calculation of SUV: body weight (SUVW), BSA (SUVBSA) and LBM (SUVLBM), with and without glucose correction, in patients with known primary lung tumor. The correlation between SUV and weight, height, blood glucose level, injected activity and time between injection and image acquisition is evaluated. Methods: Sample included 30 subjects (8 female and 22 male) with primary lung tumor, with clinical indication for 18F-FDG Positron Emission Tomography (PET). Images were acquired on a Siemens Biography according to the department’s protocol. Maximum pixel SUVW was obtained for abnormal uptake focus through semiautomatic VOI with Quantification 3D isocontour (threshold 2.5). The concentration of radioactivity (kBq/ml) was obtained from SUVW, SUVBSA, SUVLBM and the glucose corrected SUV were mathematically obtained. Results: Statistically significant differences between SUVW, SUVBSA and SUVLBM and between SUVWgluc, SUVBSAgluc and SUVLBMgluc were observed (p=0.000<0.05). The blood glucose level showed significant positive correlations with SUVW (r=0.371; p=0.043) and SUVLBM (r=0.389; p=0.034). SUVBSA showed independence of variations with the blood glucose level. Conclusion: The measurement of a radiopharmaceutical tumor uptake normalized on the basis of different distribution volumes is still variable. Further investigation on this subject is recommended.

Radon Distribution and Prevalence of Lung Cancer in Several Areas of West Georgia

ჩატარებულია რადონის განაწილების რაოდენობრივი შეფასება დასავლეთ საქართველოს ცალკეულ რაიონებში. მიღებული მონაცემები მოწმობს, რომ 100-ზე მეტი წყლის სინჯში აღინიშნება რადონის მაღალი შემცველობა. ამ უბნებთანაა დაკავშირებული ბინებში რადონის დაგროვების მაღალი მაჩვენებლები.ჩვენს მიერ ჩატარებული კვლევა კიდევ ერთხელ ადასტურებს კორელაციურ კავშირს რადონის კონცენტრაციასა და ფილტვის კიბოს გავრცელებას შორის.