Objectif : Examiner la relation entre une exposition professionnelle aux fumées de soudage au gaz et à l’arc et le risque de développer un cancer du poumon, chez des travailleurs provenant de différents milieux de travail et exposés à de nombreuses substances de différentes concentrations. Méthodes : Nous avons mené deux études cas-témoins basés sur la population montréalaise (1979-86 et 1996-2001), incluant respectivement 857 et 736 cas, ainsi que des témoins appariés selon la fréquence des cas, le sexe et le lieu de résidence. Un historique détaillé des emplois occupés fut obtenu par entrevue et évalué par une équipe d’experts afin d’estimer l’intensité, la durée ainsi que l’exposition cumulative à un grand nombre de substances. Les fumées de soudage au gaz et à l’arc sont parmi les substances évaluées et nous avons pu calculer un rapport de cote (RC) et son intervalle de confiance de 95% (IC 95%) pour le risque de cancer du poumon en utilisant la régression logistique et en ajustant pour l’historique de tabagisme et plusieurs autres covariables pertinentes. Des analyses subséquentes ont permis d’explorer d’autres voies, comme la modification des effets observés par le tabagisme. Résultats : Les résultats obtenus à partir des deux études étant assez similaires, nous avons donc pu les combiner pour former une seule étude. Aucune association statistiquement significative n’a été trouvée entre le cancer du poumon et les fumées de soudage au gaz (RC=1,13; IC 95%=0,90-1,42) et les fumées de soudage à l’arc (RC=1,01; IC 95%=0,80-1,26). Par contre, dans le sous-groupe des non-fumeurs et fumeurs très légers, nous avons trouvé un risque accru de cancer du poumon en relation avec les fumées de soudage au gaz (RC=2,78; IC 95%=1,66-4,65) et à l’arc (RC=2,20; IC 95%=1,32-3,70). En se concentrant sur ce sous-groupe, nous avons trouvé un risque encore plus élevé de développer un cancer du poumon pour ceux exposé à des doses plus substantielles, pour le soudage au gaz (RC=4,63; IC 95%=2,14-10,03) et à l’arc (RC=3,45; IC 95%=1,59-7,48). Discussion : Globalement, aucun excès de risque causé par une exposition aux fumées de soudage n’a été détecté, mais un excès a été trouvé chez les non-fumeurs et fumeurs légers uniquement et ce, pour les deux types de fumées de soudage. L’effet des fumées de soudage peut être voilé chez les fumeurs, ou bien les non-fumeurs pourraient être plus vulnérables. / Objective: To investigate the relationship between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to various agents at various concentrations and over a wide range of occupations. Methods: We conducted two population-based case-control studies in Montreal (1979-1986 and 1996-2001), including 857 and 736 cases respectively and frequency-matched controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate intensity, duration and cumulative exposure to multiple substances for each job. Gas and arc welding fumes were among the agents evaluated, and we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer using logistic regression, adjusting for smoking history and other relevant covariates. Subsequent analyses allowed us to explore other avenues, such as effect-measure modification by smoking. Results: The results from both studies were similar, so a pooled analysis was conducted. No significant association was found between lung cancer and gas welding fumes (OR=1,13; 95% CI=0,90-1,42) or arc welding fumes (OR=1,01; 95% CI=0,80-1,26). However, when restricting attention to light and non-smokers, we found an increased risk of lung cancer in relation to gas welding fumes (OR=2,78; 95% CI=1,66-4,65) and arc welding fumes (OR=2,20; 95% CI=1,32-3,70). When we further narrowed attention to workers with the highest cumulative exposures, we found even higher risk of lung cancer for gas (OR=4,63; 95% CI=2,14-10,03) and arc welding fumes (OR=3,45; 95% CI=1,59-7,48). Discussion: There was no detectable excess risk due to welding fumes among smokers; but among light and non-smokers there were excess risks related to both types of welding fumes. The effect of welding fumes may be masked in smokers or light and non-smokers may be more vulnerable.

Thesis (M.S.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 52 pages. Includes bibliographical references.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O cÃncer de pulmÃo tem sido, na Ãltima dÃcada, a principal causa de morte por cÃncer no mundo, apesar do surgimento de novos quimioterÃpicos e das terapias alvo-direcionadas. Por isso, faz-se necessÃrio o entendimento das alteraÃÃes moleculares e biolÃgicas envolvidas nos processos de carcinogÃnese e crescimento tumoral, bem como o desenvolvimento de modelos experimentais adequados que permitam estudar o comportamento biolÃgico dos tumores de pulmÃo e o efeito de drogas antineoplÃsicas. O objetivo desse estudo foi desenvolver um modelo de tumor no pulmÃo em ratos imunocompetentes de execuÃÃo simples e fÃcil reprodutibilidade, e avaliar a atividade de drogas antitumorais. Cento e noventa e um ratos Wistar fÃmeas, peso mÃdio de 199Â23g, foram distribuÃdos ao acaso em trÃs etapas experimentais. Todos os animais foram anestesiados com tribromoetanol 2,5% (1 ml/100g de rato) intraperitonial (ip), traqueostomizados e intubados com cateter de polietileno 16G, seguindo-o por via intrabrÃnquica (ib) atà as porÃÃes inferiores do pulmÃo para inocular cÃlulas do tumor 256 de Walker. A 1a etapa (n=32) foi feita para estabelecer a tÃcnica do implante de cÃlulas por via ib e o Ãndice de pega tumoral, inoculando-se de 105 a 5Ã105 cÃlulas. A 2a etapa (n=16) para avaliar o volume tumoral no 5o dia do implante de 4Ã105 cÃlulas e correlacionar os achados da tomografia computadorizada de alta resoluÃÃo (TCAR) de tÃrax com os da necropsia. A 3a etapa (n=143) para a avaliar o efeito de drogas e validar o modelo, sendo dividida em duas fases. A 1a fase (n=72) para avaliar o volume tumoral no 5o ou 6o dia do implante de 4Ã105 cÃlulas do tumor, composta de cinco grupos: Grupo controle (Gc), NaCl 0,9% (1ml/gavagem); Grupo celecoxib (Gclx), 15, 30 e 60 mg/kg/dia/gavagem; Grupo talidomida (Gtld), 45 mg/kg/d/sc; Grupo gefitinib (Ggfb), 25 mg/kg/dia; Grupo talidominda + gefititinib (Gtld +gfb). A 2a fase (n=71) para avaliar a sobrevida dos animais, com seis grupos: Gc, Gclx (15, 30, 60), Gtld, Ggfb, Gtld + gfb, Grupo paclitaxel (Gpcl), 8 mg/kg ip. O Ãndice geral de pega do tumor com o implante 4Ã105 cÃlulas foi de 96% (149/155), sendo 90% na 1a etapa, 100% na 2a etapa e 96% na 3a etapa. A mortalidade cirÃrgica foi de 4,2% (8/191) e 21 animais foram excluÃdos do estudo por ausÃncia de tumor no pulmÃo, morte por infecÃÃo (abscesso pulmonar) e outras causas nÃo relacionadas com o tumor. Na 2a etapa, as medidas do tumor feitas na TCAR e comparadas com a necropsia foram semelhantes (r=0, 953, p<0,0001). Na 1a fase da 3a etapa, nÃo se observou diferenÃa no volume tumoral dos animais dos grupos tratados em relaÃÃo ao controle; e na 2a fase verificou-se aumento significante da sobrevida mediana dos animais tratados com TLD, GFB e PCL (13, 13 e 29 dias, respectivamente), em relaÃÃo ao controle (11dias), teste de Log Rank: p<0,001. Conclui-se que o modelo de tumor de pulmÃo por implantaÃÃo de cÃlulas tumorais por via intrabrÃnquica mostrou-se viÃvel, com alto Ãndice de pega e mortalidade cirÃrgica desprezÃvel, de execuÃÃo simples e fÃcil reprodutibilidade. A TCAR revelou-se um mÃtodo de imagem de alta acurÃcia no diagnÃstico, localizaÃÃo e mensuraÃÃo das lesÃes tumorais. O modelo mostrou-se eficaz na avaliaÃÃo de atividade antitumoral de drogas antineoplÃsicas como o paclitaxel, antiangiogÃnicas como a talidomida, e inibidores de tirosina quinase do EGFR como o gefitinib. / Lung cancer has been the main cause of death from cancer worldwide over the past decade in spite of the appearance of new chemotherapy drugs and targeted therapies. It is therefore necessary to clarify the molecular and biological changes involved in carcinogenesis and tumor growth and to develop experimental models for the study of the biology of lung tumors and the effects of antineoplastic drugs. The objective of the study was to develop a practical and easily reproducible lung tumor model using immunocompetent rats and to evaluate the activity of antineoplastic drugs. One hundred ninety-one female Wistar rats, with an average weight of 199Â23g, were randomly assigned to one of three experimental groups. All animals were anesthetized intraperitonially (ip) with 2.5% tribromoetanol (1ml/100g live weight), tracheostomized and intubated with a polyethylene catheter (16G) guided intrabronchially (ib) to the bottom of the lung for inoculation with Walker 256 tumor cells. Group 1 (n=32) established the ib cell implant technique and the tumor take rate with inoculation of 105 to 5Ã105 cells. Group 2 (n=16) evaluated tumor volume on the fifth day of implant with 4Ã105 cells and correlated chest findings from high-resolution computerized tomography (HRCT) and necropsy. Group 3 (n=143) evaluated the effect of antineoplastic drugs and validated the model in two stages. Stage 1 (n=72) evaluated tumor volume on the fifth day of implant with 4Ã105 cells, divided into 5 groups: control (CG), 0.9% NaCl (1ml/gavage); celecoxib (Gclx), 15, 30 and 60mg/kg/day/gavage; thalidomide (Gtld), 45mg/kg/d/sc; gefitinib (Ggfb), 25mg/kg/day/gavage; and thalidomide + gefitinib (Gtld + gfb). Stage 2 (n=71) evaluted the survival of the animals divided into six groups: Gc, Gclx, Gtld, Ggfb, Gtld + gfb, and Gpcl (paclitaxel) 8mg/kg ip. The overal take rate for implants of 4Ã105 cells was 96% (149/155), specifically 90% in the first experimental group, 100% in the second and 96% in the third. Surgical mortality was 4.2% (8/191); 21 animals were excluded due to absence of tumor in the lung, death from infection (pulmonary abscess) and other causes not related to the tumor. In Group 2, measures obtained with HRCT and necropsy were similar (r=0, 953, p<0.0001). In the first stage of Group 3 no difference in tumor volume was observed between treated animals and controls; in the second stage median survival time was significantly extended in animals treated with TLD, GFB and PCL (13, 13 and 29 days, respectively) compared to controls (11 days) (Log Rank test: p<0.001). In conclusion, the present lung tumor model with intrabronchial tumor cell implantation was shown to be feasible and was associated with high tumor take rates, minor surgical mortality, simple execution and easy reproducibility. HRCT was found to be a highly accurate method of diagnosis, localization and tumor measurement. The model was efficient in the evaluation of the antitumoral activity of the antineoplastic drug paclitaxel, the antiangiogenic drug thalidomide, and the EGFR tyrosine kinase inhibitor gefitinib, making it a valid model for testing new drugs in lung cancer.

Orientador: Lair Zambon / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T10:28:19Z (GMT). No. of bitstreams: 1 PerroudJunior_MauricioWesley_D.pdf: 9913138 bytes, checksum: 5dd1ec64b004b6d50e2392e6383c9c98 (MD5) Previous issue date: 2012 / Resumo: Os resultados terapêuticos globais do carcinoma de pulmão não pequenas células em estádio avançado são bem limitados. A imunoterapia com células dendríticas foi desenvolvida como uma nova estratégia para o tratamento de câncer de pulmão. O objetivo deste estudo foi avaliar a viabilidade, segurança e respostas imunológicas em pacientes com carcinoma de pulmão não pequenas células tratados com vacina autóloga de células dendríticas maduras pulsadas com antígenos. Cinco pacientes HLA-A2 com carcinoma de pulmão não pequenas células inoperável (estádio III ou IV) foram selecionados para receber duas doses de 5 x 107 de células dendríticas administradas por vias subcutânea e intravenosa, duas vezes em intervalos de duas semanas. A segurança, tolerabilidade e respostas imunológica e tumoral à vacina foram avaliadas pela evolução clínica e laboratorial, ensaio de linfoproliferação e critérios de RECIST, respectivamente. A dose utilizada para a imunoterapia demonstrou ser segura e bem tolerada. O ensaio de linfoproliferação mostrou uma melhora na resposta imune específica após a imunização, com uma resposta significativa após a segunda dose (p = 0,001). Esta resposta não foi persistente e houve uma tendência à redução após duas semanas da segunda dose da vacina. Dois pacientes apresentaram uma sobrevida quase duas vezes maior que a média esperada e foram os únicos que expressaram os antígenos tumorais HER-2 e CEA Apesar do pequeno tamanho da amostra, os resultados sobre o tempo de sobrevida, resposta imune, segurança e tolerabilidade, combinado com os resultados de outros estudos, são animadores para a condução de um estudo clínico com doses múltiplas em pacientes com câncer de pulmão que foram submetidos a tratamento cirúrgico, seguindo as diretrizes do Cancer Vaccine Clinical Trial Working Group / Abstract: Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients. Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5x107 DC cells administered subcutaneous and intravenously two times at two week intervals. The safety, tolerability and immunologic and tumor responses to the vaccine were evaluated by the clinical and laboratorial evolution, lymphoproliferation assay and RECIST's criteria, respectively. The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.001). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together. Despite the small sample size, the results on the survival time, immune response, and safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment, following the guidelines of the Cancer Vaccine Clinical Trial Working Group / Doutorado / Clinica Medica / Doutor em Ciências

Lung cancer is the leading cause of cancer-related mortality worldwide. The main risk factor associated with lung cancer is cigarette smoking. Research through the years suggests that nicotine in cigarettes promotes lung cancer by activating signaling pathways that lead to cell proliferation, cell survival, angiogenesis, and metastasis. Nicotine’s cellular actions are mediated by its cognate receptors, nicotinic acetylcholine receptors (nAChRs). Here, I describe the expression levels of all known human nAChR subunit genes in both normal and lung cancer cells. Of note, the genes encoding the α5, α3, and β4 subunits (CHRNA5/A3/B4) are over-expressed in small cell lung carcinoma (SCLC), the most aggressive form of lung cancer. This over-expression is regulated by ASCL1, a transcription factor important in normal lung development and lung carcinogenesis. The CHRNA5/A3/B4 locus has recently been the focus of a series of genetic studies showing that polymorphisms in this region confer risk for both nicotine dependence and lung cancer. I show that CHRNA5/A3/B4 depletion results in decreased SCLC cell viability. Furthermore, while nicotine promotes SCLC cell viability and tumor growth, blockade of α3β4 nAChRs inhibits SCLC cell viability. These results suggest that increased expression and function of nAChRs, specifically the α3β4α5 subtype, potentiate the effects of nicotine in SCLC. This dual hit from the carcinogens in tobacco and the cancer-promoting effects of nicotine, may provide a possible mechanism for the increased aggressiveness of SCLC. In addition, nAChRs can be activated by the endogenous ligand, acetylcholine, which acts as an autocrine/paracrine growth factor in SCLC. Increased function of α3β4α5 nAChRs in SCLC could also potentiate acetylcholine’s mitogenic effects. This mechanism, combined with other known autocrine/paracrine growth loops in SCLC, may help explain the ineffectiveness of available therapies against SCLC. In an effort to add to the current arsenal against SCLC, I screened a 1280-compund library using a bioluminescence-based viability assay I developed for high-throughput applications. Primary screening, followed by secondary and tertiary verification, indicate that pharmacologically active compounds targeting neuroendocrine markers inhibit SCLC cell viability.

<p>UVOD: Drenaža grudnog ko&scaron;a nakon resekcija pluća je osnovni grudno hirur&scaron;ki postupak, koji omogućuje pro&scaron;irenje (reekspanziju) pluća iz kolabiranog stanja, evakuaciju vazduha, krvi i izliva iz pleuralnog prostora i potpomognuta je primenom aspiracije na drenove (sukciona ili aspiraciona drenaža). Iako je drenaža&nbsp; svakodnevna grudno hirur&scaron;ka procedura, postupak sa drenovima je zasnovan prvenstveno na iskustvu, a manje na osnovu naučnih studija. Pri mirnom disanju inspiratorni pritisak u pleuralnom prostoru je prosečno - 8 cm H2O, a ekspiratorni - 4 cm H2O. Pri forsiranom disanju pritisci mogu dostići - 50 cm H2O i +70 cm H2O. Na osnovu tih fiziolo&scaron;kih podataka, većina hirurga primenjuje aspiraciju od - 10 do - 40 cm H2O. Koncepta pleuralnog deficita - disproporcije volumena preostalog plućnog tkiva i zapremine grudnog ko&scaron;a doveo je do razvoja tehničkih postupaka za postizanje nove fiziolo&scaron;ke ravnoteže u pleuralnom prostoru i razmatranja rutinske primene podvodne (pasivne) drenaže nakon resekcija pluća. Pritisak na zdravstvenu službu za smanjenje tro&scaron;kova i skraćenje postoperativne hospitalizacije uz mogućnost rane mobilizacije pacijenta čine podvodnu drenažu zanimljivom alternativom tradicionalno prihvaćenoj aktivnoj aspiraciji na drenove.&nbsp; CILJ: Da se utvrdi da li aplikacija aktivne aspiracije na drenove nakon lobektomije pluća u poređenju da podvodnom drenažom ima povoljno terapijsko dejstvo na postizanje i održavanje reekspanzije pluća; Da se kvantitativno uporede različiti modovi aktivne aspiracije preko drenova; Da se uporedi dužina hospitalizacije i pojava hirur&scaron;kih i nehirur&scaron;kih komplikacija između grupa ispitanika kod kojih se primenjuje podvodna (pasivna) drenaža i aspiracija preko drenova. METODOLOGIJA: Prospektivna studija bez randomizacije obuhvatila je 301 ispitanika kojima je načinjena lobektomija pluća zbog karcinoma pluća na Klinici za grudnu hirurgiju Instituta za plućne bolesti Vojvodine u Sremskoj Kamenici u periodu od 01.01.2008. - 28.02.2010. godine. Beleženi su i analizirani podaci o preoperativnom stanju: plućnoj funkciji, prethodno primljenoj neoadjuvantnoj hemioterapiji i pridruženim bolestima. Analizirani su hirur&scaron;ki operativni podaci o postojanju buloznog emfizema, adhezija u pleuralnom prostoru, anatomskoj vrsti lobektomije, dodatnim hirur&scaron;kim procedurama i postojanju gubitka vazduha na kraju operacije. Analizirani su postoperativni podaci o secernaciji na drenove tokom prva 24 h i ukupno, trajanju gubitka vazduha na drenove u danima, ukupnom trajanju drenaže, ukupnom trajanju hospitalizacije, pojavi produženog gubitka vazduha na dren definisanog kao gubitak duže od 7 dana, potrebi za redrenažom grudnog ko&scaron;a (broj drenova upotrebljenih za redrenažu), kompletnost reekspanzije pluća pre vađenja drenova, pojavi drugih hirur&scaron;kih komplikacija, pojavi op&scaron;tih medicinskih komplikacija i pojavi kasnih komplikacija &ndash; vi&scaron;e od 30 dana nakon operacije ili nakon otpusta. Prvu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba do klemovanja i vađenja drenova. Drugu grupu ispitanika sačinjavaju pacijenti kojima je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim -10 cm vodenog stuba do klemovanja i vađenja drenova. Treću grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim podvodna drenaža do klemovanja i vađenja drenova. Četvrtu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim dnevna procena i modifikacija na sledeći način: aspiracija od -20 cm vodenog stuba do postizanja reekspanzije pluća, zatim postepeno smanjenje aspiracije po nahođenju operatera do klemovanja i vađenja drenova. REZULTATI: Između grupa ispitanika ne postoji statistički značajna razlika po starosti (p=0,77),&nbsp; parametrima plućne funkcije: vrednost FEV1 (p=0,6316), vrednost ITGV (p=0,6202), vrednost TLC (p=0,6922) i za vrednost RV ne postoji razlika (p=0,6552). Razlika ne postoji između grupa ni u učestalosti pridruženih bolesti (p=0,4522). Grupe su međusobno homogene po preoperativnim parametrima. Snižen FEV1 u ukupnoj populaciji pacijenata nije uticao na pojavu produženog gubitka vazduha (P=0,571), kao ni povi&scaron;enje ITGV (P=0,22), RV (p=0,912), niti vrednost TLC (0,521). Upoređene su međusobno osnovne vrste lobektomija: desna gornja, leva gornja, desna donja, leva donja, srednja lobektomija, kao i donja i gornja bilobektomija desno. Kako je učestalost svake pojedinačne lobektomije u 4 grupe ispitanika mali da bi se uporedile iste lobektomije između grupa, poređenje je moguće samo između anatomski različitih lobektomija kumulativno u svim grupama. Razlika u pojavi produženog gubitka vazduha između različitih lobektomija postoji, ali nije dostigla statističku značajnost (p=0,061). Međutim, kada se analizira svaka lobektomija pojedinačno, uočava se da desna donja bilobektomija ima značajno veću učestalost produženog gubitka vazduha u odnosu na sve ostale lobektomije zajedno (P=0,009). Razlika u dužini drenaže kod&nbsp; različitih lobektomija je dostigla statistički značaj (p=0,0356), kao i u ukupnoj dužini hospitalizacije (p=0,0007). Dodatak resekcije perikarda, grudnog zida ili dijafragme, klinasta resekcija susednog režnja ili sleeve resekcija bronha kao dodatne procedure nisu uticali na pojavu produženog gubitka vazduha (p=0,58). Podaci o učestalosti adhezija u ispitivanoj populaciji pacijenata i njihovom uticaju na pojavu produženog gubitka vazduha daju granične vrednosti. I ovde je broj pacijenata u svakoj pojedinačnoj kategoriji adhezija (postojanje adhezija na skali od 0-3) mali da bi testiranje povezanosti sa produženim gubitkom vazduha moglo dostići statističku značajnost - razlika postoji, ali nije značajna (p=0,065). Radi povećanja statističke snage je izvedeno testiranje za podelu ima ili nema adhezija. Razlika postoji, ali ni ovim testiranjem nije dostignuta statistički značajna razlika (p=0,057). Postojanje buloznog emfizema takođe dovodi do povećanja učestalosti produženog gubitka vazduha, ali ni ovde razlika nije značajna (p=0,063).&nbsp; Primena hemoterapije pre operacije nije dovela do statistički značajne razlike u pojavi produženog gubitka vazduha (p=0,0623) i ukupnoj stopi komplikacija (p=0,088), kao ni dužine hospitalizacije (p=0,2), iako razlika postoji i paradoksalno rezultat je bolji kod pacijenata koji su primili hemioterapiju, &scaron;to može ukazivati na uticaj selekcije pacijenata za operaciju. Između 4 grupe ispitanika nije uočena razlika u potrebi za redrenažom grudnog ko&scaron;a (p=0,101), potrebi za povećanjem nivoa aktivne aspiracije (p=0,326), ukupnoj pojavi komplikacija (p=0,087) i pojavi produženog gubitka vazduha (P=0,323). Razlika postoji i visoko je značajna u dužini trajanja drenaže (p=0,001) i dužini hospitalizacije (P=0,000). Broj drenova (1 ili 2 drena postavljena intraoperativno) nije uticao na pojavu produženog gubitka vazduha (p=0,279), ali je značajno kraća hospitalizacija kod pacijenata sa jednim drenom (p=0,0001). Logistička regresiona analiza je pokazala da je samo donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog prostora (space reducing), broja drenova i dodatne operacije (resekcije). ZAKLJUČAK: Sprovedenim istraživanjem utvrđeno je da primena aktivne aspiracije na drenove ne pokazuje razliku u odnosu na podvodnu drenažu u postizanju i održavanju reekspanzije pluća nakon lobektomije. Aktivna aspiracija ne utiče na pojavu produženog gubitka vazduha na drenove definisanog kao gubitak vazduha duže od 7 dana, ali utiče na produženje ukupnog trajanja drenaže i hospitalizacije. Nivo aktivne aspiracije ili primena dnevnih modifikacija nivoa aspiracije ne utiče na rezultate lečenja.&nbsp; U ovom istraživanju preoperativna plućna funkcija, kao ni preoperativna hemoterapija ne utiču na pojavu produženog gubitka vazduha na drenove. Desna donja bilobektomija u odnosu na sve druge lobektomije dovodi do če&scaron;će pojave produženog gubitka vazduha, produžene drenaže i hospitalizacije. Dodatne resekcije okolnih tkiva u sklopu lobektomije ili primena redukcije pleuralnog prostora ne utiču na pojavu produženog gubitka vazduha. Intraoperativni nalaz adhezija u pleuri i buloznog emfizema pluća povećavaju rizik produženog gubitka vazduha, ali je taj uticaj na granici statističke značajnosti. Primena jednog drena nakon lobektomije umesto dva ne utiče na pojavu produženog gubitka vazduha, ali utiče na skraćenje drenaže i hospitalizacije. U multivarijatnoj analizi samo je donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog, broja drenova i dodatne resekcije okolnih tkiva.</p> / <p>INTRODUCTION: The drainage of the thorax after pulmonary resection is a basic thoracic surgery procedure which enables reexpansion after lung collapse and the evacuation of air, blood and effusion from the pleural cavity. It is supported by the use of drainage aspiration (suction or aspiration drainage). Although drainage is an everyday procedure in thoracic surgery, the use of drains is based mainly on specialist experience and less on scientific research. During calm breathing the inspiratory pressure in the pleural cavity is &ndash; 8cm H2O on average, while the expiratory pressure is &ndash; 4cm H2O. During forced breathing the pressures can reach up to &ndash; 50 cm H2O and + 70 cm H2O. Based on this physiological data, most surgeons apply the aspiration from &ndash; 10 to &ndash; 40 cm H2O. The concept of pleural deficit (the disproportion of the volume of the remaining pulmonary tissue and the volume of the thorax) has attributed to development of new technical procedures in order to achieve a new physiological balance in the pleural cavity. It has also brought upon the consideration of routine underwater seal drainage after pulmonary resection. Underwater seal drainage represents an interesting alternative to the traditional active drainage aspiration, especially considering the need to reduce medical expenses and shorten the postoperative hospitalization period. AIM: To determine whether active drainage aspiration after pulmonary lobectomy has a favorable therapeutic effect on achieving and maintaining pulmonary reexpansion in comparison with underwater seal drainage; to quantitatively compare the different modes of active drainage aspiration; to compare hospitalization duration and surgical and non-surgical complication with groups of patients on whom either underwater seal drainage or aspiration drainage was applied. METHODOLOGY: The prospective study without randomization has covered 301 patients on whom pulmonary lobectomy was performed due to lung carcinoma at the Thoracic Surgery Clinic of the Institute of Pulmonary Diseases of Vojvodina from 1st January 2008 to 28th February 2010. The data collected in the pre-operative state included: pulmonary function, previous neoadjuvant chemotherapy and comorbidities. In the research, surgical operative data and postoperative data were analyzed. Surgical operative data included information about the bullous emphysema, adhesion in the pleural cavity, anatomic type of lobectomy, additional surgical procedures and air leak after surgery. Postoperative data involved information about amount of fluid on drainage during the first 24 hours and in total, air leak duration in days, total drainage period, overall hospitalization period, prolonged air leak defined as leak longer than 7 days, the need for redrainage of thorax (number of tubes used for redrainage), completeness of pulmonary reexpansion before the end of drainage, other surgical complications, comorbidities and late complications (after more than 30 days following the surgery or release). The first group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied before clamping and tube extraction. The second group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day and again &ndash; 10 cm H2O before clamping and tube extraction. The third group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day and underwater seal drainage was applied before clamping and tube extraction. The fourth group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day, and then daily monitored and modified in such a way that an aspiration of &ndash; 20 cm H2O was applied until pulmonary reexpansion and then gradually lowered according to individual surgery experience before clamping and tube extraction. RESULTS: There is no significant statistical difference between groups of patients in: age (p=0.77), FEV1 (p=0.6316), ITGV (p=0.6202), TLC (p=0.6922) and RV (p=0.6552) and comorbidities (p=0.4522). The groups are homogenous in pre-operative parameters. Lowered FEV1 among all patients did not affect prolonged air leak (p=0.571), nor the increase in values of ITGV (p=0.22), RV (p=0.912) and TLC (p=0.5211). The lobectomies that were compared were: upper right, upper left, lower right, lower left, middle, as well as upper and lower right bilobectomy. The comparison was implemented only on anatomically different lobectomies cumulatively among groups, due to the low occurrence of each type of lobectomy in groups. The difference in prolonged air leak does exist, but is not statistically significant (p=0.061). Prolonged air leak has a significantly higher occurrence in lower right bilobectomies (p=0.009). Drainage duration and hospitalization period variations in different kinds of lobectomy are statistically significant (p=0.0356 and p=0.0007, respectively). Additional pericardial, thoracic or diaphragm resection, wedge resection of the neighboring lobe, or sleeve bronchial resection did not affect prolonged air leak (p=0.58). The research has established that the occurrence of adhesion (on a scale 0-3) in patients and bulous emphysema attribute to prolonged air leak (p=0.065 and p=0.063, respectively).&nbsp; Comparison between patients with and without adhesions revealed similar result. Difference exists, but it is not statistically significant (p=0,057).&nbsp; Pre-operative chemotherapy had no statistical significance on prolonged air leak (p=0.0623), total rate of complications (p=0.088), nor hospitalization period (p=0.2). Paradoxically, the treatment was in favor of those patients who had taken pre-operative chemotherapy, which could be due to the selection of patients for surgery.&nbsp; Among the four groups, there was no difference in need for thoracic redrainage (p=0.101), need for increase in level of active aspiration (p=0.326), overall complication occurrence (p=0.087) and prolonged air leak occurrence (p=0.323). There is a statistically significant difference in drainage duration (p=0.001) and hospitalization period (p=0.000). The number of tubes (1 or 2 tubes set intraoperatively) did not affect prolonged air leak occurrence (p=0.279). The hospitalization period in patients with one tube set intraoperatively is significantly shorter (p=0.0001). Logistic regression analysis has shown that only lower bilobectomy had a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bullous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection. CONCLUSION: The research has shown: Active drainage aspiration has no difference in effect in achieving and maintaining pulmonary reexpansion after lobectomy when compared to underwater seal drainage; Active drainage aspiration does not affect prolonged air leak, defined as air leak longer than 7 days; Active drainage aspiration has an impact on the overall drainage duration and hospitalization period; The level of active drainage aspiration and daily modification of the mentioned do not affect treatment results; Preoperative pulmonary function does not affect prolonged air leak occurrence; Preoperative chemotherapy does not affect prolonged air leak occurrence; Prolonged air leak and drainage and hospitalization period occur most often in lower right bilobectomies; Nor additional resections nor pleural cavity reduction affect prolonged air leak occurrence; The presence of pleural adhesions and bullous emphysema rarely attribute to the increase of prolonged air leak occurrence; The number of tubes implemented intraoperatively does not affect prolonged air leak occurrence, but it shortens drainage and hospitalization periods; By multivariate analysis, that only lower bilobectomy has a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bulous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection.</p>

No / Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC). Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.

Chiu Yuk Lan. / "December 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 160-185) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.