<p>Karcinomi pluća su najče&scaron;ći uzrok oboljevanja i umiranja od malignih tumora u Svetu. Neodjuvantna terapija kod bolesnika sa lokalno uznapredovalim (IIIA-IIIB) karcinomom pluća i zahvaćenim N2 limfnim čvorovima jedan je od modusa multimodalnog lečenja bolesnika sa nemikrocelularnim karcinomima pluća (NSCLC) u cilju pobolj&scaron;anja ishoda njihovog lečenja. Ovakav pristup podrazumeva prevođenje bolesnika iz vi&scaron;eg u niži stadijum bolesti - &bdquo;downstaging&rdquo;. Do danas nije utvrđena povezanost između pojedinih obrazaca tumorskog odgovora i vrste terapije. S obzirom na značaj kompletnog patolo&scaron;kog odgovora i tumorske regresije u prognozi ishoda lečenja, iznalaženje ove povezanosti je od značaja za dizajniranje budućih neoadjuvantnih trajala. Prilikom utvrđivnja histolo&scaron;ke slike tumorske regresije veoma je važno i merenje areje rezidualnog tumora (ART). Kako je veličina tumora jedan od prognostičkih faktora za bolesnike sa NSCLC koji nisu primali neoadjuvantnu terapiju tako je i merenje ART, za razliku od makroskopske veličine tumora, jedan od prognostičkih faktora za bolesnike sa NSCLC koji su primali neoadjuvantnu terapiju. Krajnji cilj neoadjuvantne terapije trebalo bi da bude resektabilnost i &bdquo;downstaging&rdquo; koji bi mogao da obezbedi u specifičnim kliničkim situacijama i sveukupni onkolo&scaron;ki benefit. Osnovni ciljevi ove doktorske disertacije su bili: da se objektivizira procena veličine ART u tumorskom tkivu pluća i limfnih čvorova; da se proceni povezanost povr&scaron;ine ART sa veličinom tumora na postoperativnom hirur&scaron;kom materijalu posle neoadjuvantne terapije; da se analizira i proceni povezanost histomorfolo&scaron;kih parametara kod tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije u tumorima pluća i limfnih čvorova na&nbsp; postoperativnom hirur&scaron;kom materijalu i u zavisnosti od histolo&scaron;kog tipa karcinoma; da se proceni povezanost kliničkog odgovora na neoadjuvantnu terapiju prema kriterijumima Svetske Zdravstvene Organizacije i histolo&scaron;kih parametara u tumorima pluća i limfnim čvorovima na postoperativnom hirur&scaron;kom materijalu nakon neoadjuvantne terapije; da se proceni povezanost patolo&scaron;kog ypTN sa kliničkim ycTN stadijumom bolesti i stepena tumorske regresije indukovane neoadjuvantnom terapijom i patolo&scaron;kog ypTN i da se proceni povezanosti između kliničke i patolo&scaron;ke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Merenje ukupne veličine očuvanih ART je najznačajniji objektivni parametar u proceni stepena tumorske regresije. Veličina rezidualnog tumora nije u korelaciji sa veličinom tumora posle neoadjuvantne terapije. Postoji signifikantna razlika u patohistolo&scaron;koj slici tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije. Ne postoji signifikantna razlika između histolo&scaron;kog tipa tumora i histolo&scaron;ke slike tumorske regresije. Ne postoji signifikantna povezanost između kliničkog odgovora i stepena tumorske regresije nakon neoadjuvantne terapije. Ne postoji korelacija između kliničkog i patolo&scaron;kog stadijuma bolesti posle neoadjuvantne terapije. Ne postoji korelacija između stepena tumorske regresije indukovane neoadjuvantnom terapijom i ypTN stadijuma bolesti. Ne postoji korelacija između kliničke i patolo&scaron;ke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Stepen regresije tumora i merenje ART posle neoadjuvantne terapije određen histopatolo&scaron;kom analizom reseciranog tumora je najobjektivniji kriterijum za procenu hemioterapijskog odgovora i predviđanja ishoda lečenja pacijenata.</p> / <p>Lung cancers are the most common cause of morbidity and mortality from malignant tumors in the World. The neodjuvant therapy in patients with locally advanced (IIIA-IIIB) lung cancer and affected N2 lymph nodes is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves converting patients from a higher to a lower stage of the disease - &quot;downstaging&quot;. There has been no significant connection between some forms of tumor response and types of therapy. Given the importance of complete pathological responses and tumor regression in the prediction of treatment outcomes, finding this relationship is of importance for the design of future neoadjuvant trails. In determining the histological tumor regression is very important measurement of area of residual tumor (ART). As the size of the tumor is one of the prognostic factors in patients with NSCLC who did not receive neoadjuvant therapy so the measurement of ART, as opposed to the macroscopic size of the tumor, one of the prognostic factors in patients with NSCLC, who had received neoadjuvant therapy. The ultimate goal of neoadjuvant therapy should be resectability and &quot;downstaging&quot; that could provide overall oncology benefit in specific clinical situations. The main objectives of this thesis were: to objectively estimate the size of ART in tumor tissue of lung and lymph nodes; to estimate the relation between the surface of ART with the size of the tumor on postoperative surgical material after neoadjuvant therapy; to analyze and estimate the relation between histomorphological parameters in tumor regression induced by neoadjuvant therapy and spontaneous tumor regression in tumors of the lung and lymph nodes in the postoperative surgical material and depending on the histological type of cancer; to estimate the relation between clinical response to neoadjuvant therapy according to criteria of the World Health Organization and histological parameters in lung tumors and lymph nodes in the postoperative surgical material after neoadjuvant therapy; to estimate the correlation of the pathological ypTN with clinical ycTN stage of the disease and the degree of tumor&nbsp; regression induced by neoadjuvant therapy and pathological ypTN and estimation of the relation between clinical and pathological involvement of N2 lymph nodes after neoadjuvant therapy. Measurement of the total size of the preserved ART is the most important objective parameter in the assessment of the grade of tumor regression. Size of residual tumor did not correlate with the size of the tumor after neoadjuvant therapy. There was a significant difference in the histological picture of tumor regression induced by neoadjuvant therapy and spontaneous tumor regression. There was no significant difference between the histologic type of tumor and histological tumor regression. There is no significant correlation between clinical response and the grade of tumor regression after neoadjuvant therapy. There is no correlation between clinical and pathological staging of the disease after neoadjuvant therapy. There is no correlation between the grade of tumor regression induced by neoadjuvant therapy and ypTN stage of the disease. There is no correlation between the clinical and the pathological involvement of the N2 lymph nodes to neoadjuvant therapy. The grade of tumor regression and measurement ART after neoadjuvant therapy determined by histopathological analysis of the resected tumor is the most objective criterion for evaluation of chemotherapeutic response and prediction of treatment outcome in patients.</p>

INTRODUÇÃO: Pacientes com carcinomas das vias aerodigestivas superiores (VADS) apresentam um alto risco de desenvolver outros cânceres tanto simultaneamente quanto subsequentemente. A maioria destes tumores ocorre nas VADS, pulmões ou esôfago. A tríplice endoscopia (laringoscopia, endoscopia digestiva alta e broncoscopia) possibilita o diagnostico de lesões precursoras e de tumores invasivos. No entanto, a maioria dos estudos limita-se a descrever a frequência de diagnósticos, mas não os resultados do tratamento e o impacto na sobrevida. OBJETIVOS: Avaliar a importância da tríplice endoscopia para o diagnóstico de neoplasias primárias múltiplas e as diferenças no estadiamento e nas taxas de sobrevida de pacientes com carcinoma epidermóide de VADS. Caracterizar o perfil e analisar fatores de risco para neoplasias primárias múltiplas. MÉTODOS: Trata-se de estudo caso-controle retrospectivo em que foram incluídos pacientes com carcinoma epidermóide de VADS, submetidos à tríplice endoscopia antes do início do tratamento (grupo tríplice endoscopia), pareados, por sexo, idade e localização, estádio clínico e tratamento do tumor primário, com pacientes não submetidos à tríplice endoscopia na avaliação inicial (grupo controle). RESULTADOS: Foram incluídos 135 pacientes em cada grupo. No grupo tríplice endoscopia ocorreram mais diagnósticos de segundo tumor primário (STP), 34 (17 simultâneos e 17 metacrônicos), do que no grupo controle, 20 (1 simultâneo e 19 metacrônicos). Não foi identificada diferença significativa entre o estadiamento dos tumores de grupo tríplice endoscopia e do grupo controle. As curvas de sobrevida global, específica por câncer, livre de doença e pós-STP foram semelhantes nos dois grupos. A sobrevida livre de STP foi maior no grupo controle. Na análise multivariada foram identificados como fatores prognósticos independentes para a sobrevida, o sexo (feminino, RR 0,51, IC 0,30 0,88), a idade (maior que 57 anos, RR 1,73, IC 1,29 2,31), a localização do tumor primário (laringe, RR 0,60, IC 0,39 0,93), o estádio N (N2 e N3, RR 1,78, IC 1,26 2,51) e o estádio clínico do tumor primário (III e IV, RR 2,75, IC 1,69 4,46). As variáveis independentes relacionadas ao diagnóstico e à ocorrência de STP foram a realização de tríplice endoscopia (RR 1,93; IC 95% 1,02 - 3,65), o tipo de tratamento do tumor primário (cirurgia exclusiva, RR 3,14; IC 95% 1,11 - 8,85) e o tempo de seguimento (maior que 24 meses, RR 3,69; IC 95% 1,19 - 11,47). CONCLUSÃO: Não ocorreu diferença no estádio clínico dos STP e nas sobrevidas global, específica por câncer, livre de doença e pós-STP entre o grupo tríplice endoscopia e o grupo controle. Foram identificados como fatores independentes relacionados ao diagnóstico e a ocorrência de STP o tratamento realizado (cirurgia exclusiva), o tempo de seguimento (maior que 24 meses) e a realização da tríplice endoscopia. / INTRODUCTION: Patients with upper aerodigestive tract (UADT) carcinomas have a high risk of developing others cancers simultaneously or subsequently. Most of these tumors occur in UADT, lungs or esophagus. Triple endoscopy (laryngoscopy, endoscopy and bronchoscopy) enables the diagnosis of premalignant and invasive tumors. However, most of the studies describe only the frequency of the diagnosis, but not the results of treatment and its impact on survival. OBJECTIVES: To evaluate the importance of triple endoscopy for the diagnosis of multiple primary tumors and the differences in clinical stage and survival rates of patients with squamous cell carcinoma of the UADT. To characterize and to analyze the risk factors for multiple primary tumors. METHODS: This is a case-control study that included patients with squamous cell carcinoma of the UADT, that were submitted to a triple endoscopy before the first treatment (triple endoscopy group), matched by sex, age and location, clinical stage and treatment of primary tumor, with patients not undergoing triple endoscopy in the initial evaluation (control group). RESULTS: One hundred and thirty five patients were included in each group. The diagnosis of second primary tumor (SPT) was more frequent in the triple endoscopy group than in the control group, 34 (17 simultaneous and 17 metachronous) and 20 cases (1 simultaneous and 19 metachronous), respectively. No significant difference was found between the clinical stage of triple endoscopy group and the control group. The curves of overall survival, cancer specific, disease-free and after SPT were similar in both groups. The SPT free survival was higher in the control group. In the multivariate analysis were identified as independent prognostic factors for survival, sex (women, RR 0.51, CI 0.30 - 0.88), age (older than 57 years, RR 1.73, CI 1.29 - 2.31), the primary tumor site (larynx, RR 0.60, CI 0.39 - 0.93), N stage (N2 and N3, RR 1.78, CI 1.26 - 2.51) and the clinical stage of primary tumor (III and IV, RR 2.75, CI 1.69 - 4.46). The independent variables related to the diagnosis and the occurrence of SPT were triple endoscopy (RR 1.93, 95% CI 1.02 - 3.65), the primary tumor treatment (surgery alone, RR 3.14, 95% CI 1.11 - 8.85) and follow-up (greater than 24 months, RR 3.69, 95% CI 1.19 - 11.47). CONCLUSION: There was no difference in the clinical stage of the SPT and overall survival, cancer specific, disease-free and post SPT between the triple endoscopy group and control group. As independent predictors for the diagnosis and the occurrence of SPT were treatment performed (just surgery), follow-up time (greater than 24 months) and triple endoscopy.

Introdução: O câncer do esôfago é uma das neoplasias do aparelho digestivo com maior gravidade e que apresenta grande morbimortalidade, mesmo quando o diagnóstico é precoce. A maioria dos pacientes é diagnosticado nos estágios avançados. O tratamento depende do estadiamento da neoplasia que avalia a profundidade de invasão do tumor (T), a disseminação linfonodal (N) e a presença de metástases a distância (M) e segue as orientações da União Internacional Contra o Câncer (UICC). Nas últimas décadas o estadiamento era realizado convencionalmente pela tomografia computadorizada (TC) e atualmente com a utilização de equipamentos que avaliam o metabolismo glicolítico do tumor como o 18F-FDG-PET e o PET-CT. Este estudo teve como Objetivo avaliar a relação entre a tomografia computadorizada e os métodos metabólicos como o 18F-FDG-PET e PET-CT, no estadiamento e tratamento do Adenocarcinoma e do Carcinoma Espinocelular (CEC) do esôfago. Método: Foram avaliados 331 pacientes com diagnóstico de Adenocarcinoma e CEC do esôfago entre 2008 e 2014. Destes, 55 pacientes (16,6%) apresentaram Adenocarcinoma e 276 (83,4%) apresentaram CEC. A idade variou de 38 a 92 anos, com média de 62,9 (+/- 9,8) anos. Inicialmente foram submetidos ao estadiamento com TC e proposta de conduta cirúrgica curativa ou tratamento paliativo. Posteriormente foram avaliados com a inclusão do 18F-FDG-PET ou do PET-CT e foi definida a conduta final. Resultados: A proporção de linfonodos positivos (N+) na tomografia foi de 71%, enquanto que nos métodos metabólicos foi de 70,1% (p=0,834), contudo, com pequena concordância (Kappa=0,339). A proporção de metástases (M1) encontradas na TC foi de 44,1% e no PET-CT 47,1%. Para metástases, o teste Kappa mostrou que os dois métodos apresentam uma concordância regular (0,452), apresentando mudanças de estadiamento em 36,5% dos indivíduos, sendo 19,3% com sobre estadiamento e 17,2% com subestadiamento. Entretanto, apenas 63 pacientes (19%) apresentaram mudança de conduta final e esta foi maior nos pacientes com sobre estadiamento (67,2%) (p < 0,005). Nos pacientes com Adenocarcinoma, observou-se um número maior de subestadiamento (32,7%), comparado àqueles com CEC (15,4%) (p < 0,0001), entretanto, sem apresentar diferença estatisticamente significativa quando avaliada a mudança de conduta. Avaliando individualmente os 140 pacientes estadiados com 18F-FDG-PET, 52,9% apresentaram linfonodos positivos (N+), valor semelhante à tomografia (p=0,053), entretanto com concordância pequena, cerca de 32,9% destes com metástases (M1) (p=0,749) e com concordância regular entre os métodos. Após o estadiamento, ocorreu uma mudança de conduta de 23,6% quando avaliado por equipe multidisciplinar. Com o uso do PET-CT, a proporção de tumores T4 foi de 27,2% (p=0,071), porém, com concordância boa com a tomografia (Kappa=0,616). A proporção de linfonodos positivos (N+) foi de 82,7%, com pequena concordância com a tomografia (Kappa=0,392). A proporção de metástases (M1) no PET-CT foi de 57,6%, com concordância regular (Kappa=0,465). Apresentaram mudança de estadiamento 34% dos indivíduos, sendo 19,3% com sobre estadiamento e 14,7% com subestadiamento. Entretanto, dos 191 pacientes, apenas 30 (15,7%) apresentaram mudança de conduta final, sendo que 67,6% ocorreu nos casos com sobre estadiamento, quando comparada aos casos com subestadiamento (17,9%) (p < 0,005). Pacientes com Adenocarcinoma apresentaram um número maior de subestadiamento (30%), comparado àqueles com CEC (11,8%), (p < 0,0001), entretanto, sem apresentar diferença estatisticamente significativa. A sobrevida global, quando avaliados com PET-CT, foi em torno de 30% após 30 meses, sendo semelhante tanto no grupo de pacientes em que houve mudança de conduta quanto no grupo em que esta mudança de conduta não ocorreu. Conclusão: Conclui-se, portanto, que no estadiamento tomográfico com 18F-FDG-PET e com PET-CT foi identificado um número expressivo de pacientes em estágios avançados, entretanto estes achados muitas vezes diferem entre si. A mudança de conduta ocorre em número expressivo de pacientes e geralmente nos casos em que ocorre sobre estadiamento. Embora o Adenocarcinoma apresente um número maior de casos de subestadiamento que o CEC, esta mudança de estadiamento não se reflete na mudança de conduta quando comparados. Torna-se importante, portanto, a avaliação multiprofissional em serviço de excelência no momento de decisão sobre a melhor terapêutica. Por fim, observamos a mesma curva de sobrevida entre aqueles pacientes em que há certeza da conduta a ser tomada e aqueles em que a conduta foi mudada após o uso do PET-CT, o que corrobora a necessidade da utilização em conjunto desses dois métodos / Introduction: Esophagus cancer is one of the most serious neoplasms of the digestive tract that presents great morbidity and mortality even in early diagnosis. Most patients are diagnosed in advanced stages. Treatment depends on tumor staging, which evaluates the depth of tumor invasion (T), lymph node spread (N) and the presence of distant metastases (M) and follow the guidelines of Union for International Cancer Control (UICC). In the last decades, staging was performed conventionally by computed tomography (CT) and currently with the use of equipments that evaluates tumor glycolytic metabolism such as 18F-FDG-PET and PET-CT. This study has as main Objective to evaluate the relationship between computed tomography and metabolic methods such as 18F-FDG-PET and PET-CT in the staging and treatment of Adenocarcinoma and Spinocellular Carcinoma (SCC) of the esophagus. Method: A total of 331 patients diagnosed with adenocarcinoma and esophageal SCC were evaluated between 2008 and 2014. 55 of these patients (16.6%) had adenocarcinoma and 276 (83.4%) had CPB, ranging from 38 to 92 years, mean age of 62.9 (+/- 9.8) years. Initially they underwent staging with CT and it was proposed a curative surgical management or palliative treatment. Lately they were evaluated with the inclusion of 18F-FDG-PET or PET-CT and then the final management was defined. Results: The proportion of positive lymph nodes (N +) on the CT scan was 71%, whereas in the metabolic methods it was 70.1% (p=0.834), however, with a fair agreement (Kappa=0.339). The proportion of metastases (M1) found in CT was 44.1% and in PET-CT, 47.1%. For metastases, the Kappa test showed that the two methods presented a moderate agreement (0.452), presenting staging changes in 36.5% of subjects, being 19.3% with upstaging and 17.2% with downstaging. However, only 63 patients (19%) showed changes in the final management and this was higher in upstaging patients (67,2%) (p < 0,005). In patients with Adenocarcinoma, a greater number of downstaging was observed (32.7%), compared to those with CPB (15.4%) (p < 0.0001), however, without any statistically significant difference when the change of management was evaluated. Evaluating individually the 140 patients staged with 18F-FDG-PET, 52.9% presented positive lymph nodes (N +), data similar to tomography (p = 0.053), however with fair agreement, about 32.9% of these had metastases (M1) (P=0.749) and with moderate agreement between the methods. After the staging, a conduct change of 23.6% occurred when evaluated by a multidisciplinary team. With the use of PET-CT, the proportion of T4 tumors was 27.2% (p = 0.071), but with good agreement with tomography (Kappa=0.616). The proportion of positive lymph nodes (N+) was 82.7%, with fair agreement with the tomography (Kappa=0.392). The proportion of metastases (M1) in PET-CT was 57.6%, with moderate agreement (Kappa=0.465). 34% of the individuals presented staging change, 19.3% with upstaging and 14.7% with downstaging. However, only 30 (15.7%) out of 191 presented a final change of behavior, 67.6% of which occurred in cases with upstaging when compared to cases with downstaging (17.9%) (p < 0.005). Patients with adenocarcinoma had a greater number of downstaging (30%) compared to those with CPB (11.8%), (p < 0.0001), however, with no statistically significant difference. Overall survival when staged with PET-CT was around 30% after 30 months, being similar both in the group of patients where there was change of management and in the group where this change of management did not occur. Conclusion: It was concluded that in the tomographic staging with 18F-FDG-PET and with PET-CT an expressive number of patients in advanced stages was identified, however these findings often differ from each other. The change in management occurs in an expressive number of patients, and usually in cases where upstaging occurs. Although Adenocarcinoma presents a greater number of cases of downstaging than CPB, this change in staging is not reflected in the change of management when both are compared. It is important, therefore, the multiprofessional evaluation in service of excellence when deciding on the best therapeutics. Finally, we observed the same survival curve between those patients in which there is certainty of the management to be taken and those in which the management was changed after the use of PET-CT, which corroborates with the need to use these two methods together

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. / INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.

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Shading Accent 3"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 3"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 3"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 3"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 3"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 3"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 3"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 3"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 3"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 3"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 3"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 3"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 3"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 3"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 4"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 4"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 4"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 4"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 4"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 4"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 4"/ / <p>Free radicals are produced in our body under physiological conditions. Although in very low concentrations, they can show some toxic effects. While trying to bind electrons, in the chemical reaction of oxidation, they rapidly and unpredictably bind to adjacent molecules- proteins, lipids, carbohydrates and nucleic acids from which the structural elements of the cell are made, triggering the internal pathway of apoptosis. Antioxidants are substances that prevent or significantly reduce the oxidation of biomolecules. Oxidative stress is a condition that occurs when the production of free radicals exceeds the capacity of antioxidant enzymes to neutralize them. The antioxidant enzymes include: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST). Lipid Peroxidation (LP) is the process of oxidation of polyunsaturated fatty acids by free radicals. Malondialdehyde is a biochemical marker by which it is possible to measure the degree of oxidative damage of cell membranes. The oxidative modification of DNA leads to a change in DNA structure that results in genetic damage. The most commonly used marker of oxidative stress is urinary 8-hydroxy-2-deoxiguanosine (8-OHdG). The damage to proteins, lipids and DNA is an important basis for many diseases such as atherosclerosis, neurodegenerative diseases, diabetes, obesity, aging, retinopathy, chronic inflammatory disease and cancer. Starting from the hypothesis that these biomolecules are different at different stages of the disease, they could represent a prognostic marker of the progression of the disease. The aim of the study was to examine whether there were differences between the control group (healthy women), the patients with precancerous lesions on the cervix (HSIL), the patients with early stage cervical cancer (FIGO Ia-Ib) and the patient with locally advanced cervical cancer (IIa - IV) in the indicators of DNA damage (determining the value of 8-OHdG), indicators of oxidative stress (by determining the lipid peroxidation intensity (TBARS)), indicators of antioxidant defense (by determining the activity of antioxidative enzymes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase GPx), glutathione reductase (GR), and glutathione-S-transferase (GST)). In addition, the aim of the study was to compare the values of 8- OHdG, lipid peroxidation products (TBARS) and the activity of antioxidant enzymes (SOD, CAT, GST, GPx, GR) within the group of patients with early stage cervical cancer divided into two subgroups- with low and high risk in relation to the relapse of the disease. The research was performed at the Clinic for operative oncology, Department of Gynecology at the Institute of Oncology of Vojvodina, Medical Faculty in Novi Sad, Department of Pharmacy and the Institute for Health Care of Novi Sad in the period from 2013 to 2017. Samples of blood and urine of the patients were collected, prepared adequately and stored at -80 &deg; until the analysis. The activity of the antioxidant enzymes as well as the lipid peroxidation were determined by spectrophotometric methods, and the concentration of 8-OHdG was determined by gas chromatography with mass detection. The approval of the Ethical Committee of the Institute for Oncology of Vojvodina was obtained before conducting the research. It has been shown that there are statistically significant differences between the control group (healthy women), patient with precancerous cervical lesions (HSIL), the patients with early stage cervical cancer (FIGO Ia-Ib) compared to a group of patients with locally advanced cervical cancer (IIa-IV) in indicators of damage to DNA (concentration of 8-OHdG), indicators of oxidative stress (lipid peroxidation (TBARS)), indicators of antioxidant defense (activities of antioxidant enzymes SOD, CAT and GST). There was no difference between the groups in activity of glutathione peroxidase enzyme (GPx) and glutathione reductase (GR). There were no differences in the concentration of 8-OHdG, lipid peroxidation products (TBARS) and the activity of antioxidant enzymes (SOD, CAT, GST, GPx and GR) within the group of patients with locally restricted cervical cancer divided into two subgroups with low and high risk in relation on relapses of the disease. CAT and GST activities were the best predictors of disease recurrence among defined groups. Based on the activities of these two oxidative enzymes, the separation of the group of patients who did not experience disease recurrence after a follow-up period from the other two groups in which recurrence of the disease occurred was possible. Based on the obtained results it is concluded that it is possible to use the studied biomarkers as diagnostic markers in patients with cervical cancer. These biomolecules can help in the patient&#39;s classification into certain groups according to the stage of the disease, and consequently the more efficient choice of appropriate treatment. In addition, CAT and GST enzyme activity have been shown to be predictors of disease recurrence in defined patient groups.</p>

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. / INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. / INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.

Introdução: O câncer do esôfago é uma das neoplasias do aparelho digestivo com maior gravidade e que apresenta grande morbimortalidade, mesmo quando o diagnóstico é precoce. A maioria dos pacientes é diagnosticado nos estágios avançados. O tratamento depende do estadiamento da neoplasia que avalia a profundidade de invasão do tumor (T), a disseminação linfonodal (N) e a presença de metástases a distância (M) e segue as orientações da União Internacional Contra o Câncer (UICC). Nas últimas décadas o estadiamento era realizado convencionalmente pela tomografia computadorizada (TC) e atualmente com a utilização de equipamentos que avaliam o metabolismo glicolítico do tumor como o 18F-FDG-PET e o PET-CT. Este estudo teve como Objetivo avaliar a relação entre a tomografia computadorizada e os métodos metabólicos como o 18F-FDG-PET e PET-CT, no estadiamento e tratamento do Adenocarcinoma e do Carcinoma Espinocelular (CEC) do esôfago. Método: Foram avaliados 331 pacientes com diagnóstico de Adenocarcinoma e CEC do esôfago entre 2008 e 2014. Destes, 55 pacientes (16,6%) apresentaram Adenocarcinoma e 276 (83,4%) apresentaram CEC. A idade variou de 38 a 92 anos, com média de 62,9 (+/- 9,8) anos. Inicialmente foram submetidos ao estadiamento com TC e proposta de conduta cirúrgica curativa ou tratamento paliativo. Posteriormente foram avaliados com a inclusão do 18F-FDG-PET ou do PET-CT e foi definida a conduta final. Resultados: A proporção de linfonodos positivos (N+) na tomografia foi de 71%, enquanto que nos métodos metabólicos foi de 70,1% (p=0,834), contudo, com pequena concordância (Kappa=0,339). A proporção de metástases (M1) encontradas na TC foi de 44,1% e no PET-CT 47,1%. Para metástases, o teste Kappa mostrou que os dois métodos apresentam uma concordância regular (0,452), apresentando mudanças de estadiamento em 36,5% dos indivíduos, sendo 19,3% com sobre estadiamento e 17,2% com subestadiamento. Entretanto, apenas 63 pacientes (19%) apresentaram mudança de conduta final e esta foi maior nos pacientes com sobre estadiamento (67,2%) (p < 0,005). Nos pacientes com Adenocarcinoma, observou-se um número maior de subestadiamento (32,7%), comparado àqueles com CEC (15,4%) (p < 0,0001), entretanto, sem apresentar diferença estatisticamente significativa quando avaliada a mudança de conduta. Avaliando individualmente os 140 pacientes estadiados com 18F-FDG-PET, 52,9% apresentaram linfonodos positivos (N+), valor semelhante à tomografia (p=0,053), entretanto com concordância pequena, cerca de 32,9% destes com metástases (M1) (p=0,749) e com concordância regular entre os métodos. Após o estadiamento, ocorreu uma mudança de conduta de 23,6% quando avaliado por equipe multidisciplinar. Com o uso do PET-CT, a proporção de tumores T4 foi de 27,2% (p=0,071), porém, com concordância boa com a tomografia (Kappa=0,616). A proporção de linfonodos positivos (N+) foi de 82,7%, com pequena concordância com a tomografia (Kappa=0,392). A proporção de metástases (M1) no PET-CT foi de 57,6%, com concordância regular (Kappa=0,465). Apresentaram mudança de estadiamento 34% dos indivíduos, sendo 19,3% com sobre estadiamento e 14,7% com subestadiamento. Entretanto, dos 191 pacientes, apenas 30 (15,7%) apresentaram mudança de conduta final, sendo que 67,6% ocorreu nos casos com sobre estadiamento, quando comparada aos casos com subestadiamento (17,9%) (p < 0,005). Pacientes com Adenocarcinoma apresentaram um número maior de subestadiamento (30%), comparado àqueles com CEC (11,8%), (p < 0,0001), entretanto, sem apresentar diferença estatisticamente significativa. A sobrevida global, quando avaliados com PET-CT, foi em torno de 30% após 30 meses, sendo semelhante tanto no grupo de pacientes em que houve mudança de conduta quanto no grupo em que esta mudança de conduta não ocorreu. Conclusão: Conclui-se, portanto, que no estadiamento tomográfico com 18F-FDG-PET e com PET-CT foi identificado um número expressivo de pacientes em estágios avançados, entretanto estes achados muitas vezes diferem entre si. A mudança de conduta ocorre em número expressivo de pacientes e geralmente nos casos em que ocorre sobre estadiamento. Embora o Adenocarcinoma apresente um número maior de casos de subestadiamento que o CEC, esta mudança de estadiamento não se reflete na mudança de conduta quando comparados. Torna-se importante, portanto, a avaliação multiprofissional em serviço de excelência no momento de decisão sobre a melhor terapêutica. Por fim, observamos a mesma curva de sobrevida entre aqueles pacientes em que há certeza da conduta a ser tomada e aqueles em que a conduta foi mudada após o uso do PET-CT, o que corrobora a necessidade da utilização em conjunto desses dois métodos / Introduction: Esophagus cancer is one of the most serious neoplasms of the digestive tract that presents great morbidity and mortality even in early diagnosis. Most patients are diagnosed in advanced stages. Treatment depends on tumor staging, which evaluates the depth of tumor invasion (T), lymph node spread (N) and the presence of distant metastases (M) and follow the guidelines of Union for International Cancer Control (UICC). In the last decades, staging was performed conventionally by computed tomography (CT) and currently with the use of equipments that evaluates tumor glycolytic metabolism such as 18F-FDG-PET and PET-CT. This study has as main Objective to evaluate the relationship between computed tomography and metabolic methods such as 18F-FDG-PET and PET-CT in the staging and treatment of Adenocarcinoma and Spinocellular Carcinoma (SCC) of the esophagus. Method: A total of 331 patients diagnosed with adenocarcinoma and esophageal SCC were evaluated between 2008 and 2014. 55 of these patients (16.6%) had adenocarcinoma and 276 (83.4%) had CPB, ranging from 38 to 92 years, mean age of 62.9 (+/- 9.8) years. Initially they underwent staging with CT and it was proposed a curative surgical management or palliative treatment. Lately they were evaluated with the inclusion of 18F-FDG-PET or PET-CT and then the final management was defined. Results: The proportion of positive lymph nodes (N +) on the CT scan was 71%, whereas in the metabolic methods it was 70.1% (p=0.834), however, with a fair agreement (Kappa=0.339). The proportion of metastases (M1) found in CT was 44.1% and in PET-CT, 47.1%. For metastases, the Kappa test showed that the two methods presented a moderate agreement (0.452), presenting staging changes in 36.5% of subjects, being 19.3% with upstaging and 17.2% with downstaging. However, only 63 patients (19%) showed changes in the final management and this was higher in upstaging patients (67,2%) (p < 0,005). In patients with Adenocarcinoma, a greater number of downstaging was observed (32.7%), compared to those with CPB (15.4%) (p < 0.0001), however, without any statistically significant difference when the change of management was evaluated. Evaluating individually the 140 patients staged with 18F-FDG-PET, 52.9% presented positive lymph nodes (N +), data similar to tomography (p = 0.053), however with fair agreement, about 32.9% of these had metastases (M1) (P=0.749) and with moderate agreement between the methods. After the staging, a conduct change of 23.6% occurred when evaluated by a multidisciplinary team. With the use of PET-CT, the proportion of T4 tumors was 27.2% (p = 0.071), but with good agreement with tomography (Kappa=0.616). The proportion of positive lymph nodes (N+) was 82.7%, with fair agreement with the tomography (Kappa=0.392). The proportion of metastases (M1) in PET-CT was 57.6%, with moderate agreement (Kappa=0.465). 34% of the individuals presented staging change, 19.3% with upstaging and 14.7% with downstaging. However, only 30 (15.7%) out of 191 presented a final change of behavior, 67.6% of which occurred in cases with upstaging when compared to cases with downstaging (17.9%) (p < 0.005). Patients with adenocarcinoma had a greater number of downstaging (30%) compared to those with CPB (11.8%), (p < 0.0001), however, with no statistically significant difference. Overall survival when staged with PET-CT was around 30% after 30 months, being similar both in the group of patients where there was change of management and in the group where this change of management did not occur. Conclusion: It was concluded that in the tomographic staging with 18F-FDG-PET and with PET-CT an expressive number of patients in advanced stages was identified, however these findings often differ from each other. The change in management occurs in an expressive number of patients, and usually in cases where upstaging occurs. Although Adenocarcinoma presents a greater number of cases of downstaging than CPB, this change in staging is not reflected in the change of management when both are compared. It is important, therefore, the multiprofessional evaluation in service of excellence when deciding on the best therapeutics. Finally, we observed the same survival curve between those patients in which there is certainty of the management to be taken and those in which the management was changed after the use of PET-CT, which corroborates with the need to use these two methods together

INTRODUÇÃO: Pacientes com carcinomas das vias aerodigestivas superiores (VADS) apresentam um alto risco de desenvolver outros cânceres tanto simultaneamente quanto subsequentemente. A maioria destes tumores ocorre nas VADS, pulmões ou esôfago. A tríplice endoscopia (laringoscopia, endoscopia digestiva alta e broncoscopia) possibilita o diagnostico de lesões precursoras e de tumores invasivos. No entanto, a maioria dos estudos limita-se a descrever a frequência de diagnósticos, mas não os resultados do tratamento e o impacto na sobrevida. OBJETIVOS: Avaliar a importância da tríplice endoscopia para o diagnóstico de neoplasias primárias múltiplas e as diferenças no estadiamento e nas taxas de sobrevida de pacientes com carcinoma epidermóide de VADS. Caracterizar o perfil e analisar fatores de risco para neoplasias primárias múltiplas. MÉTODOS: Trata-se de estudo caso-controle retrospectivo em que foram incluídos pacientes com carcinoma epidermóide de VADS, submetidos à tríplice endoscopia antes do início do tratamento (grupo tríplice endoscopia), pareados, por sexo, idade e localização, estádio clínico e tratamento do tumor primário, com pacientes não submetidos à tríplice endoscopia na avaliação inicial (grupo controle). RESULTADOS: Foram incluídos 135 pacientes em cada grupo. No grupo tríplice endoscopia ocorreram mais diagnósticos de segundo tumor primário (STP), 34 (17 simultâneos e 17 metacrônicos), do que no grupo controle, 20 (1 simultâneo e 19 metacrônicos). Não foi identificada diferença significativa entre o estadiamento dos tumores de grupo tríplice endoscopia e do grupo controle. As curvas de sobrevida global, específica por câncer, livre de doença e pós-STP foram semelhantes nos dois grupos. A sobrevida livre de STP foi maior no grupo controle. Na análise multivariada foram identificados como fatores prognósticos independentes para a sobrevida, o sexo (feminino, RR 0,51, IC 0,30 0,88), a idade (maior que 57 anos, RR 1,73, IC 1,29 2,31), a localização do tumor primário (laringe, RR 0,60, IC 0,39 0,93), o estádio N (N2 e N3, RR 1,78, IC 1,26 2,51) e o estádio clínico do tumor primário (III e IV, RR 2,75, IC 1,69 4,46). As variáveis independentes relacionadas ao diagnóstico e à ocorrência de STP foram a realização de tríplice endoscopia (RR 1,93; IC 95% 1,02 - 3,65), o tipo de tratamento do tumor primário (cirurgia exclusiva, RR 3,14; IC 95% 1,11 - 8,85) e o tempo de seguimento (maior que 24 meses, RR 3,69; IC 95% 1,19 - 11,47). CONCLUSÃO: Não ocorreu diferença no estádio clínico dos STP e nas sobrevidas global, específica por câncer, livre de doença e pós-STP entre o grupo tríplice endoscopia e o grupo controle. Foram identificados como fatores independentes relacionados ao diagnóstico e a ocorrência de STP o tratamento realizado (cirurgia exclusiva), o tempo de seguimento (maior que 24 meses) e a realização da tríplice endoscopia. / INTRODUCTION: Patients with upper aerodigestive tract (UADT) carcinomas have a high risk of developing others cancers simultaneously or subsequently. Most of these tumors occur in UADT, lungs or esophagus. Triple endoscopy (laryngoscopy, endoscopy and bronchoscopy) enables the diagnosis of premalignant and invasive tumors. However, most of the studies describe only the frequency of the diagnosis, but not the results of treatment and its impact on survival. OBJECTIVES: To evaluate the importance of triple endoscopy for the diagnosis of multiple primary tumors and the differences in clinical stage and survival rates of patients with squamous cell carcinoma of the UADT. To characterize and to analyze the risk factors for multiple primary tumors. METHODS: This is a case-control study that included patients with squamous cell carcinoma of the UADT, that were submitted to a triple endoscopy before the first treatment (triple endoscopy group), matched by sex, age and location, clinical stage and treatment of primary tumor, with patients not undergoing triple endoscopy in the initial evaluation (control group). RESULTS: One hundred and thirty five patients were included in each group. The diagnosis of second primary tumor (SPT) was more frequent in the triple endoscopy group than in the control group, 34 (17 simultaneous and 17 metachronous) and 20 cases (1 simultaneous and 19 metachronous), respectively. No significant difference was found between the clinical stage of triple endoscopy group and the control group. The curves of overall survival, cancer specific, disease-free and after SPT were similar in both groups. The SPT free survival was higher in the control group. In the multivariate analysis were identified as independent prognostic factors for survival, sex (women, RR 0.51, CI 0.30 - 0.88), age (older than 57 years, RR 1.73, CI 1.29 - 2.31), the primary tumor site (larynx, RR 0.60, CI 0.39 - 0.93), N stage (N2 and N3, RR 1.78, CI 1.26 - 2.51) and the clinical stage of primary tumor (III and IV, RR 2.75, CI 1.69 - 4.46). The independent variables related to the diagnosis and the occurrence of SPT were triple endoscopy (RR 1.93, 95% CI 1.02 - 3.65), the primary tumor treatment (surgery alone, RR 3.14, 95% CI 1.11 - 8.85) and follow-up (greater than 24 months, RR 3.69, 95% CI 1.19 - 11.47). CONCLUSION: There was no difference in the clinical stage of the SPT and overall survival, cancer specific, disease-free and post SPT between the triple endoscopy group and control group. As independent predictors for the diagnosis and the occurrence of SPT were treatment performed (just surgery), follow-up time (greater than 24 months) and triple endoscopy.

<p>&Scaron;irom sveta, karcinom bronha je i dalje vodeći po incidenci i mortalitetu, sa 2,1 milion novih slučajeva i predviđenih 1,8 smrtnih ishoda u 2018. godini. Karcinom bronha predstavlja skoro petinu (18,4%) svih smrtnih ishoda od karcinoma. Istraživanje je sprovedeno kao retrospektivna studija za period 2010-2016 godine. Svi podaci potrebni za sprovođenje ovog istraživanja direktno su prikupljeni iz zdravstvenog informacionog sistema i registra za karcinom bronha Instituta za plućne bolesti Vojvodine (IPBV), koji je referentna ustanova za pacijente sa karcinomom bronha za celu Autonomnu Pokrajinu Vojvodinu. Cilj rada je bio da se utvrdi uticaj demografskih i kliničko-patololo&scaron;kih karakteristika na ukupno vreme preživljavanja kod bolesnika sa karcinomom bronha, kao i da se izradi geoprostorna analiza incidencije i mortaliteta od karcinoma bronha na teritoriji Vojvodine. Podaci o broju novoobolelih i broju umrlih pacijenata potrebni za analizu incidencije i mortaliteta prikupljeni su od lokalnih Instituta za javno zdravlje za svaki od sedam okruga. Za potrebe analize overall survivall, survival rate ukupno je obuhvaćeno 8142 bolesnika lečenih u IPBV, od kojih je nakon provere uključujućih i isključujućih kriterijuma, u konačnu analizu u&scaron;lo njih 7540. Za potrebe analize incidencije i mortaliteta prikupljeni su podaci od lokalnih Instituta za javno zdravlje za svaki od sedam okruga i ukupno je uključeno 21915 pacijenata. Od ukupno 7540 bolesnika, bilo je 5456 (72,4%) mu&scaron;karaca i 2084 (27,6%) žena. Prosečna starost bolesnika iznosila je 63,4&plusmn;8,85 godina, Najveći broj bolesnika su bili pu&scaron;ači, njih 4911 (65,1%), biv&scaron;ih pu&scaron;ača je bilo 1995 (26,5%), dok je najmanje bilo nepu&scaron;ača, svega 634 (8,4%). Srednja vrednost indeksa paklo-godina (pack-years) iznosila je 50,57&plusmn;28,80. Posmatrano prema bračnom statusu, najvi&scaron;e bolesnika je bilo oženjeno/udato, njih 5348 (70,9%). Najveći broj bolesnika je ocenio svoj socioekonomski status kao osrednji, njih 4912 (65,1%). Broj bolesnika sa ECOG performans statusom 1 bio je 5679 (75,3%), njih 840 (11,1%) je imalo ECOG performans status 2, dok je ECOG performans status 0 imao 451 (6,0%) bolesnik. Najveći broj bolesnika bio je dijagnostikovan u IV stadijumu bolesti 3108 (41,2%), zatim u IIIB 1886 (25,0%), IIIA 1401 (18,6%), dok je u IA stadijumu dijagnostikovano najmanje bolesnika, njih 234 (3,1%). Najveći broj bolesnika imao je potvrđenu dijagnozu adenokarcinoma, njih 3342 (44,3%), zatim skvamoznog karcinoma 2472 (32,8%), mikrocelularnog karcinoma 1386 (18,4%). Od ukupnog broja bolesnika, tokom perioda praćenja preminulo je njih 6420 (85,1%), dok je 1120 (14,9%) bolesnika bilo živo. Prosečno vreme preživljavanja mu&scaron;karaca bilo je 17,116 meseci, a žena 23,193 meseca. Mu&scaron;karci oboleli od karcinoma bronha statistički značajno (p=0,000) kraće su živeli u odnosu na žene. Analiza kumulativnog preživljavanja bolesnika pokazala je da je postojala statistički značajna razlika u preživljavanju u odnosu na pol kod podtipova adenokarcinom (p=0,000), skvamozni karcinom (p=0,000) i mikrocelularni karcinom (p=0,001). Statistički značajna razlika u preživljavanju postojala je i u odnosu na starost, mesto stanovanja, tip tumora, stadijum bolesti, ECOG, pu&scaron;ački status i TNM stadijum bolesti (p=0,000). Ukupno jednogodi&scaron;nje preživljavanje obolelih od karcinoma bronha iznosilo je 32,5%, skvamoznog karcinoma 37,3%, adenokarcinoma 33,4% i mikrocelularnog karcinoma 20,9%. Ukupno trogodi&scaron;nje preživljavanje obolelih od karcinoma bronha iznosilo je 9,2%, skvamoznog karcinoma 10,8%, adenokarcinoma 10,7% i mikrocelularnog karcinoma 2,0%. Ukupno petogodi&scaron;nje preživljavanje obolelih od karcinoma bronha iznosilo je 5,0%, kod skvamoznog karcinoma 6,1%, adenokarcinoma 5,4% i mikrocelularnog karcinoma 1,3%. Ukupno jednogodi&scaron;nje preživljavanje obolelih od karcinoma bronha u 1A stadijumu iznosilo je 78,1%, u 1B stadijumu 73,2%, 2A stadijumu 70,4%, 2B stadijumu 52,1%, 3A stadijumu 42,3%, 3B stadijumu 28,3%, dok je u 4 stadijumu bolesti ukupno jednogodi&scaron;nje preživljavanje bilo 17,9%. Ukupno trogodi&scaron;nje preživljavanje obolelih od karcinoma bronha u 1A stadijumu iznosilo je 40,8%, u 1B stadijumu 37,5%, 2A stadijumu 31,2%, 2B stadijumu 21,6%, 3A stadijumu 9,7%, 3B stadijumu 5,5%, dok je u 4 stadijumu bolesti ukupno trogodi&scaron;nje preživljavanje bilo 2,9%. Ukupno petogodi&scaron;nje preživljavanje obolelih od karcinoma bronha u 1A stadijumu iznosilo je 32,1%, u 1B stadijumu 19,3%, 2A stadijumu 16,2%, 2B stadijumu 13,3%, 3A stadijumu 4,4%, 3B stadijumu 2,6%, dok je u 4 stadijumu bolesti ukupno petogodi&scaron;nje preživljavanje bilo 1,6%. Kao nezavisni prediktori preživljavanja izdvojeni su mu&scaron;ki pol, starost preko 60 godina, ECOG performans status veći od 2, pu&scaron;ačka navika, lo&scaron;iji socioekonomski status, stadijum IV bolesti, T4 status, M1b status i mikrokarcinom kao tip tumora (p=0,000). Incidencija karcinoma bronha za mu&scaron;karce iznosila je 118,9 na 100000 stanovnika, a za žene 43,3 na 100000 stanovnika. Standardizovana stopa incidencije karcinoma bronha za mu&scaron;karce iznosila je 65,4 na 100000 stanovnika, a za žene 21,7 na 100000 stanovnika. Prema okruzima je postojala statistički značajna razlika (p=0,001). Stopa mortaliteta od karcinoma bronha za mu&scaron;karce iznosila 125,1 na 100000 stanovnika, a za žene 43,8 na 100000 stanovnika. Standardizovana stopa mortaliteta od karcinoma bronha za mu&scaron;karce iznosila 67,6 na 100000 stanovnika, a za žene 20,9 na 100000 stanovnika. Prema okruzima je postojala statistički značajna razlika (p=0,001). Analizom prikupljenih podataka utvrđeno je da postoji statistički značajna razlika u ukupnom vremenu preživljavanja pacijenata sa dijagnostikovanim karcinomom bronha u odnosu na pol (p=0,000), starosnu dob (p=0,000), mesto stanovanja (p=0,014), pu&scaron;ački status (p=0,001), ECOG performans status (p=0,000) i socioekonosmski status (p=0,000). Postoji statistički značajna razlika u ukupnom vremenu preživljavanja pacijenata sa dijagnostikovanim karcinomom bronha u odsnosu na tip tumora (p=0,000), stadijum bolesti (p=0,000), T-deskriptor (p=0,000), N-deskriptor (p=0,000) i M-deskriptor (p=0,000). Utvrđeno je da ukupno jednogodi&scaron;nje preživljavanje obolelih od karcinoma bronha iznosi 32,5%, trogodi&scaron;nje preživljavanje obolelih od karcinoma bronha iznosi 9,2%, a petogodi&scaron;nje preživljavanje iznosi 5,0%. Utvrđeno je da su nezavisni prediktori preživljavanja mu&scaron;ki pol, starost preko 60 godina, ECOG performans status 2 i veći, pu&scaron;ačka navika, lo&scaron;iji socioekonomski status, stadijum IV bolesti, T4 status, M1b status i mikroculularni karcinom kao tip tumora. Urađena je analiza incidencije i mortaliteta od karcinoma bronha na teritoriji AP Vojvodine i utvrđeno je da postoje značajne regionalne razlike u incidenciji i mortalitetu od karcinoma bronha na teritoriji AP Vojvodine.</p> / <p>Worldwide, lung cancer remains the leading cause of cancer incidencije and mortality, with 2.1 million new lung cancer cases and 1.8 million deaths predicted in 2018. Methodology: For the purpose of this retrospective study we collected data of 21915 patients from seven Public Health Institutes, one for each district. This data was categorized by five-year age groups during 2010&ndash;2016. Survival analysis data of 8142 patients was collected from the Institute for Pulmonary Diseases of Vojvodina Hospital Information System and the Lung Cancer Registry. The primary objective was to determine the impact on overall survival by assessing demographic and clinical pathological characteristics in these patients. The secondary objective was to analyze the incidencije and mortality of lung cancer in the region of Vojvodina. Incidencije and mortality rates were directly age-standardized to the World and Europe Standard Population. A total of 7540 patients were eligible for the survival analysis, 5456 (72.4%) males and 2084 (27.6%) females. The average survival time, including all stages and cancer types was 17.1 months for men and 23.2 months for women (p = 0.000). There was statistically significant difference in survival time by gender in subtypes of adenocarcinoma (p = 0.000), squamous cell carcinoma (p= 0.000) and microcellular carcinoma (p = 0.001). Analysis showed significant difference in survival by age (p = 0.000), cancer type (p = 0.000), stage of the disease (p = 0.000), ECOG performance status (p = 0.000), smoking status (p = 0.001), TNM stage of disease (p = 0.000) and among districts (p = 0.014). Male gender (p = 0.000), age over 60 (p = 0.000), ECOG performance status 2 and greater (p = 0.000), smoking habit (p = 0.002), lower socioeconomic status (p = 0.000), stage IV of disease (p = 0.000) and small cell lung cancer as tumor type (p = 0.000) were identified as independent prognostic factors. One-year survival in 1A stage was 78.1%, in 1B stage 73.2%, 2A stage 70.4%, 2B stage 52.1%, 3A stage 42.3%, 3B stage 28.3 %, while in stage 4 was 17.9%. Three-year survival in 1A stage was 40.8%, in 1B stage 37.5%, 2A stage 31.2%, 2B stage 21.6%, 3A stage 9.7%, 3B stage 5.5 %, while in stage 4 was 2.9%. Five-year in 1A stage is 32.1%, in 1B stage 19.3%, 2A stage 16.2%, 2B stage 13.3%, 3A stage 4.4%, 3B stage 2.6 %, while in stage 4 was 1.6%. The incidencije rate was 118.9 per 100000 for males and 43.3 per 100000 for women. The standardized incidencije rate was 65.4 per 100000 for males and 21.7 per 100000 for females. There was a statistically significant difference by districts (p = 0.001). Mortality rate was 125.1 per 100000 for males and 43.8 per 100000 for females. The standardized mortality rate was 67.6 per 100000 for males and 20.9 per 100000 for females. There was also a statistically significant difference by district (p = 0.001). There was a statistically significant difference in overall survival by gender (p = 0.000), age (p = 0.000), place of residence (p = 0.014), smoking status (p = 0.001), ECOG performance status (p = 0.000), and socioeconomic status (p = 0.000). There was also a statistically significant difference in the overall survival by tumor type (p = 0.000), stage of disease (p = 0.000), T-descriptor (p = 0.000), N-descriptor (p = 0.000), and M-descriptor (p = 0.000). One-year survival rate was 32.5%, three-year survival was 9.2%, and five-year survival rate was 5.0%. Incidencije and mortality rates data were analyzed for the territory of Vojvodina, and it was found that there were significant regional differences.</p>