INTRODUÇÃO: Nos pacientes com câncer de próstata considerados de baixo risco, a braquiterapia de baixa taxa de dose (BBTD) utilizando sementes de 125I é uma excelente opção, com seguimento após o tratamento, devendo ser feito por meio de medidas seriadas de PSA. A avaliação de falha bioquímica após radioterapia, definida por elevação do PSA, tem sido feita pelo critério da ASTRO (American Society for Therapeutic Radiology and Oncology) e, mais recentemente, pelo critério do consenso de Phoenix. OBJETIVOS: Avaliar a sobrevida livre de falha bioquímica (SLFB) de pacientes submetidos à BBTD pelos critérios ASTRO e Phoenix e as relações entre eles com as falhas clínicas. Correlacionar essas sobrevidas com idade, grau histológico de Gleason, estadiamento clínico, PSA inicial, porcentagem de fragmentos positivos na biópsia, invasão perineural, volume prostático na ultra-sonografia diagnóstica, hormonioterapia neoadjuvante, bounce e D90 (dose recebida por 90% do volume de próstata). MÉTODO: Estudo retrospectivo de 329 pacientes tratados, entre julho de 1998 e dezembro de 2002, no serviço de Radioterapia do Hospital Sírio-Libanês, São Paulo. Foram excluídos 18 pacientes que tinham recebido braquiterapia associada à RT externa, 18 pacientes classificados como de alto risco, 61 casos com menos de dois anos de seguimento mínimo e 12, com dados incompletos nos prontuários. Portanto, 220 pacientes formaram a base desta análise. RESULTADOS: Cento e vinte e um (55%) pacientes foram classificados como de baixo risco e 99 (45%) de risco intermediário. O seguimento mediano foi de 53,5 meses (24 a 116); 74 pacientes (33,6%) fizeram algum tipo de bloqueio hormonal por um tempo mediano de 90 dias e 66 pacientes (30%) apresentaram bounce. O tempo médio para o aparecimento do bounce foi de 15 meses, com um nadir médio de 0,30ng/mL. A SLFB em cinco anos pelo critério ASTRO foi de 83% e de 88,3% pelo Phoenix (p < 0,05). Para os pacientes de risco baixo e intermediário, respectivamente, 86,7% e 78,4% pela definição ASTRO (p = 0,069) e 88,5% e 77,9% de acordo com Phoenix (p = 0,016). Na análise multivariada, PSA inicial < 10 ng/mL e porcentagem de fragmentos positivos < 50% foram fatores prognósticos favoráveis em relação à falha (p < 0,05) pelo critério ASTRO. De acordo com o critério Phoenix, PSA inicial < 10 ng/mL, grau histológico de Gleason < 7, porcentagem de fragmentos positivos < 50% e grupo de baixo risco foram os fatores independentes favoráveis, preditivos de falha bioquímica (p < 0,05). CONCLUSÕES: Os dados de sobrevida livre de falha bioquímica em cinco anos para pacientes de risco baixo e intermediário desta análise foram comparáveis aos da literatura. Nesta análise, não houve diferença entre as definições ASTRO e Phoenix de falha. PSA, escore de Gleason, porcentagem de fragmentos positivos na biópsia e grupo de risco foram os fatores prognósticos independentes para falha bioquímica. / INTRODUCTION: Patients with low-risk prostate adenocarcinoma may be very well treated by low dose-rate brachytherapy (LDR) using 125I seeds. Follow-up with periodical serum prostate specific antigen (PSA) dosages is used to determine the effectiveness of treatment. Biochemical relapse may be defined either by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, or, more recently, by the Phoenix Consensus criteria. PURPOSE: To evaluate and compare biochemical failure-free survival (BFFS) of patients treated with LDR brachytherapy using ASTRO and Phoenix criteria. Also, to correlate BFFS with age, Gleason score, clinical stage, initial PSA, percentage of positive prostate biopsies, perineural invasion, prostate volume at diagnostic ultrasound, neoadjuvant hormone therapy, bounce, and D90 (dose received by 90% of the prostate). METHODS: A cohort of 329 patients who received LDR brachytherapy for prostate cancer, between 1998 and 2002 at Hospital Sírio-Libanês, São Paulo, was retrospectively studied. Eighteen patients who received external beam irradiation were excluded, together with another 18 high-risk patients, 61 with less than 2 years minimal followup, and 12 with incomplete record data. So, 220 patients were the basis of this study. RESULTS: One hundred and twenty one (55%) were low-risk patients and 99 (45%) were intermediate-risk. Median follow-up was 53.5 months (24-116); 74 (33.6%) patients received neoadjuvant hormone therapy during a median period of 90 days, and 66 (30%) presented bounce. Mean time till bounce was 15 months, with mean nadir of 0,30ng/mL. The 5-year BFFS was 83% using ASTRO criteria, and 88.3% using Phoenix (p > 0,05). Low and intermediate-risk patients presented, respectively, 86.7% and 78.4% 5-year BFFS using ASTRO definition (p = 0,069), and 88.5% and 77.9%, considering Phoenix criteria (p = 0,016). In multivariate analysis, initial PSA < 10 ng/mL, and percentage of positive prostate biopsies < 50% were favorable prognostic factors, regarding biochemical relapse using ASTRO criteria (p < 0,05), while initial PSA < 10 ng/mL, Gleason score < 7, percentage of positive prostate biopsies < 50%, and low-risk group were detected as independent favorable prognostic factors using Phoenix definition (p < 0,05). CONCLUSIONS: The 5-year estimates of BFFS using both criteria, for low and intermediate-risk patients, were similar to previous published data, with no significant difference between them. Initial PSA, Gleason score, percentage of positive prostate biopsies, and risk group were independent prognostic factors for biochemical relapse.

Estudo retrospectivo de 119 pacientes com diagnóstico de adenocarcinoma ductal invasivo no estádio clínico III tratadas com quimioterapia neoadjuvante (FEC), mastectomia e adjuvância. Destas, 85 optaram por reconstrução mamária imediata (RMI) com retalho transverso músculo-cutâneo de reto-abdominal e 34, não. Com seguimento médio de 52,7 meses avaliou-se o tempo de hospitalização, a inter-relação com a adjuvância, recidiva local, o tempo livre de doença e o tempo total de sobrevida, concluindo-se que, apesar de aumentar o tempo de hospitalização, a RMI não interfere com os demais ítens, podendo ser indicada para pacientes portadoras de carcinoma mamário em estádio clínico avançado / A retrospective study with 119 patients diagnosed with invasive ductal adenocarcinoma of the breast treated with neoadjuvant chemotherapy (FEC), mastectomy and adjuvant therapy. Eight-five patients chose immediate breast reconstruction (IBR) with transverse rectus abdominis myocutaneous flap and, 34 did not do it. The mean follow-up was 52.7 months. Length of stay, adjuvant therapy interrelation, local recurrence, disease-free survival and overall survival were evaluated. It was concluded that despite a longer stay, IBR did not interfere with any of the other factors analyzed and may be indicated for patients with advanced breast disease

INTRODUÇÃO: Nos pacientes com câncer de próstata considerados de baixo risco, a braquiterapia de baixa taxa de dose (BBTD) utilizando sementes de 125I é uma excelente opção, com seguimento após o tratamento, devendo ser feito por meio de medidas seriadas de PSA. A avaliação de falha bioquímica após radioterapia, definida por elevação do PSA, tem sido feita pelo critério da ASTRO (American Society for Therapeutic Radiology and Oncology) e, mais recentemente, pelo critério do consenso de Phoenix. OBJETIVOS: Avaliar a sobrevida livre de falha bioquímica (SLFB) de pacientes submetidos à BBTD pelos critérios ASTRO e Phoenix e as relações entre eles com as falhas clínicas. Correlacionar essas sobrevidas com idade, grau histológico de Gleason, estadiamento clínico, PSA inicial, porcentagem de fragmentos positivos na biópsia, invasão perineural, volume prostático na ultra-sonografia diagnóstica, hormonioterapia neoadjuvante, bounce e D90 (dose recebida por 90% do volume de próstata). MÉTODO: Estudo retrospectivo de 329 pacientes tratados, entre julho de 1998 e dezembro de 2002, no serviço de Radioterapia do Hospital Sírio-Libanês, São Paulo. Foram excluídos 18 pacientes que tinham recebido braquiterapia associada à RT externa, 18 pacientes classificados como de alto risco, 61 casos com menos de dois anos de seguimento mínimo e 12, com dados incompletos nos prontuários. Portanto, 220 pacientes formaram a base desta análise. RESULTADOS: Cento e vinte e um (55%) pacientes foram classificados como de baixo risco e 99 (45%) de risco intermediário. O seguimento mediano foi de 53,5 meses (24 a 116); 74 pacientes (33,6%) fizeram algum tipo de bloqueio hormonal por um tempo mediano de 90 dias e 66 pacientes (30%) apresentaram bounce. O tempo médio para o aparecimento do bounce foi de 15 meses, com um nadir médio de 0,30ng/mL. A SLFB em cinco anos pelo critério ASTRO foi de 83% e de 88,3% pelo Phoenix (p < 0,05). Para os pacientes de risco baixo e intermediário, respectivamente, 86,7% e 78,4% pela definição ASTRO (p = 0,069) e 88,5% e 77,9% de acordo com Phoenix (p = 0,016). Na análise multivariada, PSA inicial < 10 ng/mL e porcentagem de fragmentos positivos < 50% foram fatores prognósticos favoráveis em relação à falha (p < 0,05) pelo critério ASTRO. De acordo com o critério Phoenix, PSA inicial < 10 ng/mL, grau histológico de Gleason < 7, porcentagem de fragmentos positivos < 50% e grupo de baixo risco foram os fatores independentes favoráveis, preditivos de falha bioquímica (p < 0,05). CONCLUSÕES: Os dados de sobrevida livre de falha bioquímica em cinco anos para pacientes de risco baixo e intermediário desta análise foram comparáveis aos da literatura. Nesta análise, não houve diferença entre as definições ASTRO e Phoenix de falha. PSA, escore de Gleason, porcentagem de fragmentos positivos na biópsia e grupo de risco foram os fatores prognósticos independentes para falha bioquímica. / INTRODUCTION: Patients with low-risk prostate adenocarcinoma may be very well treated by low dose-rate brachytherapy (LDR) using 125I seeds. Follow-up with periodical serum prostate specific antigen (PSA) dosages is used to determine the effectiveness of treatment. Biochemical relapse may be defined either by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, or, more recently, by the Phoenix Consensus criteria. PURPOSE: To evaluate and compare biochemical failure-free survival (BFFS) of patients treated with LDR brachytherapy using ASTRO and Phoenix criteria. Also, to correlate BFFS with age, Gleason score, clinical stage, initial PSA, percentage of positive prostate biopsies, perineural invasion, prostate volume at diagnostic ultrasound, neoadjuvant hormone therapy, bounce, and D90 (dose received by 90% of the prostate). METHODS: A cohort of 329 patients who received LDR brachytherapy for prostate cancer, between 1998 and 2002 at Hospital Sírio-Libanês, São Paulo, was retrospectively studied. Eighteen patients who received external beam irradiation were excluded, together with another 18 high-risk patients, 61 with less than 2 years minimal followup, and 12 with incomplete record data. So, 220 patients were the basis of this study. RESULTS: One hundred and twenty one (55%) were low-risk patients and 99 (45%) were intermediate-risk. Median follow-up was 53.5 months (24-116); 74 (33.6%) patients received neoadjuvant hormone therapy during a median period of 90 days, and 66 (30%) presented bounce. Mean time till bounce was 15 months, with mean nadir of 0,30ng/mL. The 5-year BFFS was 83% using ASTRO criteria, and 88.3% using Phoenix (p > 0,05). Low and intermediate-risk patients presented, respectively, 86.7% and 78.4% 5-year BFFS using ASTRO definition (p = 0,069), and 88.5% and 77.9%, considering Phoenix criteria (p = 0,016). In multivariate analysis, initial PSA < 10 ng/mL, and percentage of positive prostate biopsies < 50% were favorable prognostic factors, regarding biochemical relapse using ASTRO criteria (p < 0,05), while initial PSA < 10 ng/mL, Gleason score < 7, percentage of positive prostate biopsies < 50%, and low-risk group were detected as independent favorable prognostic factors using Phoenix definition (p < 0,05). CONCLUSIONS: The 5-year estimates of BFFS using both criteria, for low and intermediate-risk patients, were similar to previous published data, with no significant difference between them. Initial PSA, Gleason score, percentage of positive prostate biopsies, and risk group were independent prognostic factors for biochemical relapse.

O tratamento cirúrgico do adenocarcinoma da junção esofagogástrica (AJEG) ainda é controverso, particularmente, em relação à sobrevida e complicações pós-operatórias. Com o advento da cirurgia minimamente invasiva e toracoscopia, houve um aumento da linfadenectomia e menores complicações, entretanto seu impacto na sobrevida do AEGJ é pouco conhecido. Objetivos: Comparar a esofagectomia por via transtorácica por toracoscopia (grupo A) com esofagectomia por via transhiatal (grupo B) em pacientes com AJEG em relação a ocorrência de complicações e mortalidade; número de linfonodos ressecados, acometidos e relação ressecados e acometidos; sobrevidas global e livre de doença; e sobrevida após recidiva. Métodos: Foram selecionados 147 pacientes entre 2000 e 2016. Cento e trinta (88%) do sexo masculino, média de idade de 64 anos. Os dados epidemiológicos (idade, sexo, índice de massa corpórea, ECOG e antecedentes pessoais) foram avaliados e comparados entre os grupos. As complicações pós-operatórias (fistula cervical, quilotorax, complicações respiratórias, rouquidão e infecções cirúrgicas) foram avaliadas. O estadiamento anátomo-patológico foi avaliado pela 7a. edição AJCC, analisando os linfonodos ressecados, acometidos e a relação de ressecados e acometidos. Foram feitas análises da sobrevivência global, livre de doença, e após recidiva; além de análise multivariada de fatores relacionados à sobrevida. Resultados: Em relação aos dados epidemiológicos, o grupo A apresentava uma média de idade de 61,1 anos e grupo B, de 65,7 anos (p=0,009). Dos 54 pacientes do grupo A, 47 (87,0%) foram submetidos a tratamento neoadjuvante, contra 43 (46,3%) dos 93 pacientes do grupo B (p < 0,001). Em relação às complicações, o grupo A apresentou maior ocorrência de rouquidão e infecções cirúrgicas. Em relação à mortalidade, o grupo A apresentou dois casos (3,7%) e grupo B apresentou quatro (4,3%), sem diferença estatística. Não houve diferença estatística entre os grupos A e B quanto à localização topográfica do tumor, grau histológico, pT, pN, estádio, extensão do tumor, invasão linfática, venosa e perineural. No grupo A, a média de linfonodos ressecados foi 31,88 linfonodos e no grupo B 20,73 linfonodos (p < 0,001); entretanto a média de linfonodos acometidos no grupo A foi 3,96 linfonodos e no grupo B 4,25 linfonodos, sem diferença estatística, bem como a razão ressecados acometidos. A sobrevida global geral foi 42,3%, nos grupo A, 38,9% e no grupo B, 7,6% (p=0,298). Na análise multivariada da sobrevida global somente a invasão linfática (p=0,005), diabetes mellitus (p=0,038) e infecção cirúrgica (p=0,001) foram significantes. A sobrevida livre de doença geral foi 45,6%, no grupo A 40% e grupo B 46% (p=0,77) e, na multivariada, somente a invasão linfática (p=0,01) e o diabetes mellitus (p=0,049) foram significantes. Entretanto nos tumores com estádio até 2B a sobrevida global do grupo A foi 80,4% e do grupo B, 38,5% (p=0,001). A sobrevida após recidiva foi melhor na recidiva pulmonar, seguida pela hepática ou mediastinal e peritoneal (p=0,001). Conclusão: Ambos os métodos são seguros com taxas de morbidade e mortalidade semelhantes. A esofagectomia por toracoscopia permite uma ressecção maior do número de linfonodos. As sobrevidas globais e livres de doença são semelhantes, entretanto até o estádio 2B a esofagectomia por toracoscopia melhora a sobrevida global. Diabetes e invasão linfática interferem na sobrevida global e livre de doença / The surgical treatment of adenocarcinoma of the esophagogastric junction surgical treatment (AGEJ) is still controversial, particularly concerning to survival and postoperative complications. With the advent of minimally invasive surgery and thoracoscopy, there has been an increase in lymphadenectomy and less complications, however its impact on survival of AGEJ is still unknown. Objectives: To compare transthoracic thoracoscopic esophagectomy (group A) with transhiatal esophagectomy (group B) in patients with AGEJ in relation to the occurrence of complications and mortality; number of ressected lymph nodes, the positive and the ratio between the ressected and positive; overall and disease free survival; and survival after relapse. Methods: There was a selection of 147 patients from 2000 to 2016. One hundred and thirty (88%) were male, the average age was 64 years old. Epidemiological data (age, sex, body mass index, ECOG and past medical history) were analyzed and compared between the groups. Postoperative complications (cervical fistulae, chylothorax, respiratory complications, hoarseness and surgical infections) were evaluated. The anatomopathological staging was evaluated by the 7th UICC edition, analyzing the resected lymph nodes, the affected and the ratio between the resected and affected. Analysis of overall survival, disease free survival and survival after relapse were made, besides multivariate analysis of survival related factors. Results: In relation to the epidemiological data, group A presented an average age of 61.1 years, and group B of 65.7 years (p=0.009). 47 (87.0%) of the 54 patients in group A were submitted to neoadjuvant treatments, against 43 (46.3%) of the 93 patients in group B (p < 0.001). In relation to the complications, group A presented greater occurrence of hoarseness and surgical infections. In relation to mortality, group A presented 2 cases (3.7%) and group B presented 4 (4.3%), without statistical difference. There was no statistical difference between groups A and B about topographic location of the tumor, histologic grade, pT, pN, stage, tumor extension, lymphatic, venous or perineural invasion. In group A, the average number of ressected lymph nodes was 31.88 and in group B was 20.73 (p < 0.001), however the average number of affected lymph nodes was 3.96 in group A and 4.25 in group B, without statistical difference, as well as the ratio between ressected and affected lymph nodes. The general overall survival was 42.3%, in group A was 38.9% and in group B was 47.6% (p=0.298). In the multivariate analysis of overall survival only lymphatic invasion (p=0.005), diabetes mellitus (p=0.038) and surgical infection (p- 0.001) were significant. The general disease free survival was 45.6%, in group A was 40% and in group B was 46% (p=0.77) and in multivariate analysis only lymphatic invasion (p=0.01) and diabetes mellitus (p=0.049) were significant. However, in tumors with stage until 2B, group A overall survival was 80.4% and group B was 38.5% (p=0.001). Survival after relapse was better in pulmonary relapse, followed by hepatic or mediastinal and peritoneal (p=0.001). Conclusion: Both methods are safe with similar morbidity and mortality rates. Transthoracic thoracoscopic esophagectomy allows a larger ressection in the number of lymph nodes. Overall survival and disease free survival are similar, however until stage 2B thoracoscopic esophagectomy improves overall survival. Diabetes and lymphatic invasion interfere in overall and disease free survival

Aufgrund ihres sehr hohen Metastasierungsrisikos weisen Patienten mit klarzelligem Nierenzellkarzinom (kzNZK) eine sehr hohe Sterblichkeit auf. Mit den zurzeit zur Verfügung stehenden klinischen Parametern kann der Krankheitsverlauf der Patienten nach der operativen Entfernung des Primärtumors nur unzureichend vorhergesagt werden. Um das Nachsorge- und Therapieregime der Patienten zu optimieren, muss die Vorhersagegenauigkeit der bestehenden Prognosemodelle durch molekulare Marker erhöht werden. Um geeignete Gene für eine Abschätzung von Metastasierungsrisiko und krankheitsfreiem Überleben (DFS) zu identifizieren, wurden genomweite Expressionsanalysen sowohl an Lungenmetastasen (n = 24) als auch an Primärtumoren (n = 24) des kzNZK vorgenommen. Durch Vergleich von Metastasensubgruppen, die sich nach unterschiedlich langen DFS entwickelt hatten bzw. Primärtumoren, die nach unterschiedlich langen DFS Metastasen bedingten, wurden tumorintrinsische DFS-assoziierte Expressionsmuster identifiziert. Weiterhin wurden Gene identifiziert, deren Expression sich zwischen Primärtumoren unterschied, die im Krankheitsverlauf manifeste Metastasen bedingten und solchen, die dies nicht taten. Die differenzielle Expression funktionell interessanter, teilweise auch in anderen publizierten Microarraystudien an kzNZK bestätigter Gene wurde im Folgenden mittels quantitativer Polymerasekettenreaktion (qPCR) validiert. Anschließend wurde die Assoziation ausgewählter Gene mit klinischen Parametern und dem Überleben der Patienten untersucht. Ein von klinischen Parametern unabhängiger Einfluss auf den Krankheitsverlauf der Patienten wurde dabei für EDNRB und PECAM1 auf Expressionsebene (qPCR; n = 86) sowie für TSPAN7 auf Proteinebene (Immunhistochemie an „Tissue Microarrays“; n = 106) belegt. EDNRB und PECAM1 waren signifikant höher exprimiert in Primärtumoren mit günstigen klinischen Parametern (TNMI/II, G1/2, V0, N0/M0). TSPAN7 war vorwiegend in den Gefäßen der primären kzNZK nachweisbar; eine signifikant höhere Zahl TSPAN7-positiver Gefäße war ebenfalls in Tumoren mit günstigen klinischen Parametern zu verzeichnen (pT1/2, TNMI/II, N0). Überlebensanalysen zeigten ein signifikant längeres DFS für Patienten mit einer hohen im Vergleich zu solchen mit einer geringen EDNRB-Expression und für Patienten, die in beiden untersuchten Gewebestanzen der „Tissue Microarrays“ TSPAN7-positive Gefäße aufwiesen im Vergleich zu Patienten mit nur einer oder keiner TSPAN7-gefäßpositiven Stanze. Für Patienten mit einer hohen im Vergleich zu solchen mit einer geringen EDNRB- bzw. PECAM1-Expression oder mit zwei im Vergleich zu keiner oder einer TSPAN7-gefäßpositiven Gewebestanze war zudem ein signifikant längeres tumorspezifisches Überleben (TSS) zu verzeichnen. Mit Hilfe multivariater Cox-Regressionsanalysen wurde eine unabhängige günstige prognostische Relevanz für EDNRB auf das DFS sowie für EDNRB, PECAM1 und TSPAN7 auf das TSS nachgewiesen. Somit sind diese molekularen Faktoren geeignet, um die Genauigkeit der bestehenden und ausschließlich auf klinischen Parametern basierenden Prognosemodelle zu erhöhen. Für eine Abschätzung von DFS und Metastasierungsrisiko erscheint dabei insbesondere EDNRB geeignet. / Patients with clear cell renal cell carcinoma (ccRCC) have an extremely poor prognosis due to their high risk of metastases. Currently used clinico-patological parameters are insufficient for reliable prediction of metastatic risk and disease free survival (DFS) after surgical resection of the primary tumor. Molecular markers are strongly needed to improve outcome prediction, and thus to optimize the follow up and treatment schedule for patients with ccRCC. To identify genes which are suitable for the prediction of metastatic risk and DFS, genome-wide expression analyses were performed on pulmonary metastases (n = 24) and primary tumors (n = 24) obtained from patients with ccRCC. Tumor-intrinsic DFS-associated expression patterns were observed by comparing subgroups of metastases, which had developed within different DFS as well as primary tumors, which had caused metastases after different DFS. Furthermore, genes differentially expressed in primary tumors, which caused macroscopic metastases and tumors, which did not were identified. The differential expression of genes with a potential function in metastatic spread, which has in part been identified in independent published microarray studies as well, were validated by quantitative polymerase chain reaction (qPCR). Moreover, an independent prognostic impact on the survival of ccRCC patients was observed for the EDNRB und the PECAM1 gene expression (qPCR; n = 86) as well as for the TSPAN7 protein level (immunohistochemistry on tissue microarrays; n = 106). Primary tumors of patients with favourable clinico-pathological parameters (TNMI/II, G1/2, V0, N0/M0) showed a significantly higher EDNRB und PECAM1 gene expression than those with unfavorable parameters. TSPAN7 was predominantly detected in blood vessels of ccRCC tissues. In patients with favourable clinico-pathological parameters (pT1/2, TNMI/II, N0) a significantly higher number of TSPAN7-positive vessels was observed. Using survival analyses, a significantly longer DFS was observed for patients with a high compared to those with a low EDNRB expression as well as for patients with TSPAN7-positive vessels in both cores compared to no or one of the both cores investigated on tissue microarrays. A significantly longer TSS was observed for patients with a high EDNRB or PECAM1 expression as well as for patients with TSPAN7-positive vessles in both tissue cores investigated. Furthermore, EDNRB was an independent prognostic factor for the DFS of the patients; EDNRB, PECAM and TSPAN7 had an independent prognostic impact on the TSS. Therefore, these molecular markers are suitable to improve the accuracy of outcome prediction based on clinico-pathological parameters in ccRCC. For the prediction of DFS and metastatic risk EDNRB is particularly interesting.

Estudo retrospectivo de 119 pacientes com diagnóstico de adenocarcinoma ductal invasivo no estádio clínico III tratadas com quimioterapia neoadjuvante (FEC), mastectomia e adjuvância. Destas, 85 optaram por reconstrução mamária imediata (RMI) com retalho transverso músculo-cutâneo de reto-abdominal e 34, não. Com seguimento médio de 52,7 meses avaliou-se o tempo de hospitalização, a inter-relação com a adjuvância, recidiva local, o tempo livre de doença e o tempo total de sobrevida, concluindo-se que, apesar de aumentar o tempo de hospitalização, a RMI não interfere com os demais ítens, podendo ser indicada para pacientes portadoras de carcinoma mamário em estádio clínico avançado / A retrospective study with 119 patients diagnosed with invasive ductal adenocarcinoma of the breast treated with neoadjuvant chemotherapy (FEC), mastectomy and adjuvant therapy. Eight-five patients chose immediate breast reconstruction (IBR) with transverse rectus abdominis myocutaneous flap and, 34 did not do it. The mean follow-up was 52.7 months. Length of stay, adjuvant therapy interrelation, local recurrence, disease-free survival and overall survival were evaluated. It was concluded that despite a longer stay, IBR did not interfere with any of the other factors analyzed and may be indicated for patients with advanced breast disease

O tratamento cirúrgico do adenocarcinoma da junção esofagogástrica (AJEG) ainda é controverso, particularmente, em relação à sobrevida e complicações pós-operatórias. Com o advento da cirurgia minimamente invasiva e toracoscopia, houve um aumento da linfadenectomia e menores complicações, entretanto seu impacto na sobrevida do AEGJ é pouco conhecido. Objetivos: Comparar a esofagectomia por via transtorácica por toracoscopia (grupo A) com esofagectomia por via transhiatal (grupo B) em pacientes com AJEG em relação a ocorrência de complicações e mortalidade; número de linfonodos ressecados, acometidos e relação ressecados e acometidos; sobrevidas global e livre de doença; e sobrevida após recidiva. Métodos: Foram selecionados 147 pacientes entre 2000 e 2016. Cento e trinta (88%) do sexo masculino, média de idade de 64 anos. Os dados epidemiológicos (idade, sexo, índice de massa corpórea, ECOG e antecedentes pessoais) foram avaliados e comparados entre os grupos. As complicações pós-operatórias (fistula cervical, quilotorax, complicações respiratórias, rouquidão e infecções cirúrgicas) foram avaliadas. O estadiamento anátomo-patológico foi avaliado pela 7a. edição AJCC, analisando os linfonodos ressecados, acometidos e a relação de ressecados e acometidos. Foram feitas análises da sobrevivência global, livre de doença, e após recidiva; além de análise multivariada de fatores relacionados à sobrevida. Resultados: Em relação aos dados epidemiológicos, o grupo A apresentava uma média de idade de 61,1 anos e grupo B, de 65,7 anos (p=0,009). Dos 54 pacientes do grupo A, 47 (87,0%) foram submetidos a tratamento neoadjuvante, contra 43 (46,3%) dos 93 pacientes do grupo B (p < 0,001). Em relação às complicações, o grupo A apresentou maior ocorrência de rouquidão e infecções cirúrgicas. Em relação à mortalidade, o grupo A apresentou dois casos (3,7%) e grupo B apresentou quatro (4,3%), sem diferença estatística. Não houve diferença estatística entre os grupos A e B quanto à localização topográfica do tumor, grau histológico, pT, pN, estádio, extensão do tumor, invasão linfática, venosa e perineural. No grupo A, a média de linfonodos ressecados foi 31,88 linfonodos e no grupo B 20,73 linfonodos (p < 0,001); entretanto a média de linfonodos acometidos no grupo A foi 3,96 linfonodos e no grupo B 4,25 linfonodos, sem diferença estatística, bem como a razão ressecados acometidos. A sobrevida global geral foi 42,3%, nos grupo A, 38,9% e no grupo B, 7,6% (p=0,298). Na análise multivariada da sobrevida global somente a invasão linfática (p=0,005), diabetes mellitus (p=0,038) e infecção cirúrgica (p=0,001) foram significantes. A sobrevida livre de doença geral foi 45,6%, no grupo A 40% e grupo B 46% (p=0,77) e, na multivariada, somente a invasão linfática (p=0,01) e o diabetes mellitus (p=0,049) foram significantes. Entretanto nos tumores com estádio até 2B a sobrevida global do grupo A foi 80,4% e do grupo B, 38,5% (p=0,001). A sobrevida após recidiva foi melhor na recidiva pulmonar, seguida pela hepática ou mediastinal e peritoneal (p=0,001). Conclusão: Ambos os métodos são seguros com taxas de morbidade e mortalidade semelhantes. A esofagectomia por toracoscopia permite uma ressecção maior do número de linfonodos. As sobrevidas globais e livres de doença são semelhantes, entretanto até o estádio 2B a esofagectomia por toracoscopia melhora a sobrevida global. Diabetes e invasão linfática interferem na sobrevida global e livre de doença / The surgical treatment of adenocarcinoma of the esophagogastric junction surgical treatment (AGEJ) is still controversial, particularly concerning to survival and postoperative complications. With the advent of minimally invasive surgery and thoracoscopy, there has been an increase in lymphadenectomy and less complications, however its impact on survival of AGEJ is still unknown. Objectives: To compare transthoracic thoracoscopic esophagectomy (group A) with transhiatal esophagectomy (group B) in patients with AGEJ in relation to the occurrence of complications and mortality; number of ressected lymph nodes, the positive and the ratio between the ressected and positive; overall and disease free survival; and survival after relapse. Methods: There was a selection of 147 patients from 2000 to 2016. One hundred and thirty (88%) were male, the average age was 64 years old. Epidemiological data (age, sex, body mass index, ECOG and past medical history) were analyzed and compared between the groups. Postoperative complications (cervical fistulae, chylothorax, respiratory complications, hoarseness and surgical infections) were evaluated. The anatomopathological staging was evaluated by the 7th UICC edition, analyzing the resected lymph nodes, the affected and the ratio between the resected and affected. Analysis of overall survival, disease free survival and survival after relapse were made, besides multivariate analysis of survival related factors. Results: In relation to the epidemiological data, group A presented an average age of 61.1 years, and group B of 65.7 years (p=0.009). 47 (87.0%) of the 54 patients in group A were submitted to neoadjuvant treatments, against 43 (46.3%) of the 93 patients in group B (p < 0.001). In relation to the complications, group A presented greater occurrence of hoarseness and surgical infections. In relation to mortality, group A presented 2 cases (3.7%) and group B presented 4 (4.3%), without statistical difference. There was no statistical difference between groups A and B about topographic location of the tumor, histologic grade, pT, pN, stage, tumor extension, lymphatic, venous or perineural invasion. In group A, the average number of ressected lymph nodes was 31.88 and in group B was 20.73 (p < 0.001), however the average number of affected lymph nodes was 3.96 in group A and 4.25 in group B, without statistical difference, as well as the ratio between ressected and affected lymph nodes. The general overall survival was 42.3%, in group A was 38.9% and in group B was 47.6% (p=0.298). In the multivariate analysis of overall survival only lymphatic invasion (p=0.005), diabetes mellitus (p=0.038) and surgical infection (p- 0.001) were significant. The general disease free survival was 45.6%, in group A was 40% and in group B was 46% (p=0.77) and in multivariate analysis only lymphatic invasion (p=0.01) and diabetes mellitus (p=0.049) were significant. However, in tumors with stage until 2B, group A overall survival was 80.4% and group B was 38.5% (p=0.001). Survival after relapse was better in pulmonary relapse, followed by hepatic or mediastinal and peritoneal (p=0.001). Conclusion: Both methods are safe with similar morbidity and mortality rates. Transthoracic thoracoscopic esophagectomy allows a larger ressection in the number of lymph nodes. Overall survival and disease free survival are similar, however until stage 2B thoracoscopic esophagectomy improves overall survival. Diabetes and lymphatic invasion interfere in overall and disease free survival

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-09-04T15:39:47Z No. of bitstreams: 1 homerogoncalvesjunior.pdf: 2526505 bytes, checksum: e3bc0f5bc2176febea8072cc318baab6 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-09-04T15:52:35Z (GMT) No. of bitstreams: 1 homerogoncalvesjunior.pdf: 2526505 bytes, checksum: e3bc0f5bc2176febea8072cc318baab6 (MD5) / Made available in DSpace on 2018-09-04T15:52:35Z (GMT). No. of bitstreams: 1 homerogoncalvesjunior.pdf: 2526505 bytes, checksum: e3bc0f5bc2176febea8072cc318baab6 (MD5) Previous issue date: 2018-07-06 / O tratamento do câncer de mama baseia-se na classificação dos casos, em termos de estadiamento e do perfil biomolecular. Os Tumores Triplo Negativos (TTN) representam um grupo especial de neoplasias mamárias que não expressam receptores hormonais e nem o antígeno Her2. São considerados agressivos e de pior evolução, e quando estudados em particular, apresentam muita heterogeneidade. Importa saber se a caracterização dos tumores como Triplo Negativos, é suficiente para delimitar o grupo em termos de prognóstico e terapêutica. Este estudo teve como objetivo comparar os aspectos clínico-epidemiológicos dos Tumores Triplo Negativos em relação aos Não Triplo Negativos, em coorte de mulheres com câncer de mama assistidas em centros oncológicos de referência de Juiz de Fora, Minas Gerais. A sobrevida global e a sobrevida livre de doença foram calculadas pelo método de Kaplan Meier, e as curvas de sobrevida foram avaliadas pelo teste de Log-Rank, nos subgrupos Triplo Negativos e Não Triplo Negativos (NTN). Os fatores prognósticos foram comparados pelo modelo de riscos proporcionais de Cox. Os Tumores Triplo Negativos apresentaram diferenças demográficas em relação aos NTN, com acúmulo de pacientes não brancas e de baixo nível sociocultural; e ainda com aspectos de maior gravidade ao diagnóstico. A evolução também foi pior, tanto em termos de sobrevida global quanto sobrevida livre de doença dentre os TTN. Na análise univariada, os fatores: idade, cor da pele, escolaridade, tamanho do tumor e grau tumoral, estado das axilas e estadiamento, bem como taxas elevadas dos marcadores P53 e Ki 67, se mostraram associados a sobrevida livre de doença nos Tumores Não Triplo Negativos. No cálculo da sobrevida global, essas variáveis se mantiveram, exceto a idade; e foi constatado maior risco para as mulheres oriundas do serviço público de saúde, bem como o surgimento de metástases no decurso do seguimento. Para os Triplo Negativos, a análise univariada mostrou influência do estado axilar e estadiamento na sobrevida livre de doença; e os mesmos fatores acrescidos do surgimento de metástases, para a sobrevida global. Na análise multivariada a escolaridade e o estado axilar representaram risco à sobrevida livre de doença para NTN, enquanto a cor da pele e o estadiamento para a sobrevida global. Quanto aos TTN, sua evolução se mostrou ligada a dois aspectos: o comprometimento axilar para sobrevida livre de doença e global; e também a multicentricidade para a sobrevida global. Os Tumores Triplo Negativos aparentam ter biologia bem diversa dos Não Triplo Negativos, na dependência dos componentes histológicos e moleculares que portam. A classificação molecular por imunoistoquímica se mostrou capaz de identificar os dois grupos tumorais e auxiliar na orientação terapêutica. / Current breast cancer treatment is based on the classification of tumor stage and molecular profile. Triple-negative breast cancer (TNBC) is a specific subset of tumors characterized by the absence of hormone and HER2 receptors. Despite being usually associated with a more aggressive clinical course, there is high heterogeneity within TNBC. Therefore, it has been questioned whether current classification of TNBC is adequate enough to assess its prognosis and make therapeutic decisions. This study thus aimed to investigate to which extent TNBC profile classification was able to efficiently distinguish this tumor subtype from other subtypes of breast cancer. It was performed on a cohort of women with breast cancer treated at referral centers in Juiz de Fora, Southeastern Brazil. Overall and disease-free survival and prognostic factors were assessed and compared for TNBC and non-TNBC. Survival functions were calculated using the Kaplan-Meier method, and the log-rank test was used to compare the survival curves. Prognostic factors were analyzed by the Cox proportional hazards model. TNBC presented demographic differences compared to non-TNBC as it was more prevalent among nonwhite and less educated women. TNBC also presented at diagnosis with clinical parameters of advanced disease and had overall and disease-free survival significantly lower than non-TNBC. In univariate analysis the factors: age, color of the skin, education level, size and degree of tumor, axillary status and staging, as well as high rates of P53 e Ki 67 have been shown to be associated with disease-free survival in non-TNBC. These variables remained the same in the calculation of overall survival except for age; and it was also observed a greater risk for women from the public health service as well as the appearance of metastases during the follow-up. In multivariate analysis education level and axillary lymph node involvement presented a risk for disease-free survival while the color of skin and staging, for overall survival in non-TNBC. Regarding TNBC, its evolution was related to two aspects: axillary impairment for disease-free and global survival and multicentricity for overall survival. TNBC presents distinct biological properties compared to non-TNBC, which seems to be related to its specific histological and molecular components. The molecular classification by immunohistochemistry showed to be able to identify the two tumor groups and to support the therapeutic orientation.

<p>UVOD: Karcinom kolona (KK) je velik javnozdravstveni problem usled visoke incidence i stope mortaliteta. Kod KK je stadijum bolesti najvažniji pojedinačni nezavisni faktor prognoze. U prisustvu nepovoljnih prognostičkih parametara, u koje spadaju visok histolo&scaron;ki gradus, ileus, limfo-vaskularna i perineuralna invazija, nakon potencijalno kurativne operacije se kod pacijenata u stadijumu II indikuje primena adjuvantne hemioterapije koja ima pozitivan uticaj na ukupno preživljavanje i na produženje perioda bez bolesti. Međutim, relapsi bolesti nastaju kod nekih bolesnika bez negativnih prognostičkih faktora, &scaron;to ukazuje na moguće postojanje drugih tkivnih faktora lo&scaron;e prognoze. U novije vreme se sve veća pažnja posvećuje fenomenu tumorskog pupljenja koje predstavlja pojavu tumorskih pupoljaka (TP), odnosno oligocelularnih grupa tumorskih ćelija koje se na invazivnom frontu tumora odvajaju od glavne tumorske mase. Ove tumorske ćelije poprimaju fenotip mezenhimnih ćelija i stiču sposobnost ameboidnog kretanja kroz ekstracelularni matriks, uz pomoć citoplazmatskih podija koje se na dvodimenzionalnim histolo&scaron;kim rezovima vizualizuju kao citoplazmatski pseudofragmenti (CPF). Značaj gustine TP i CPF je jo&scaron; uvek nedovoljno ispitan, ali postoje indicije da se radi o moćnom prediktoru biolo&scaron;kog pona&scaron;anja tumora. CILJ: Cilj je bio da se ispita zavisnost dužine perioda bez relapsa, veličine primarnog tumora, gustine peritumorske limfocitne infiltracije i konfiguracije tumorske margine od gustine TP i CPF kod bolesnika sa KK u stadijumu II. METODOLOGIJA: Istraživanjem je obuhvaćeno 114 bolesnika operisanih od KK u stadijumu II na Institutu za onkologiju Vojvodine, bez nepovoljnih prognostičkih faktora i bez indikacija za primenu adjuvantne hemioterapije. Mikroskopskom analizom rutinskih histolo&scaron;kih i imunohistohemijskih preparata utvrđivana je gustina TP i CPF, koja je zatim korelirana sa vremenom pojave relapsa, veličinom primarnog tumora, gustinom peritumorske limfocitne infiltracije i konfiguracijom tumorske margine. REZULTATI: Velika gustina TP i/ili CPF nađena je kod 45 tumora (39,5%). U ovoj grupi se relaps dogodio kod 26 bolesnika (57,8%). U grupi bolesnika sa malom gustinom TP/CPF relaps je registrovan u 4 slučaja (5,8%). Poređenje krivih preživljavanja pokazalo je da je verovatnoća relapsa značajno veća ako se u tumoru nalazi velika gustina TP/CPF (p&lt;0,0001). Tumori sa velikom gustinom TP/CPF su imali najveći prečnik koji je varirao u rasponu od 25 do 100 mm, dok su tumori sa malom gustinom TP/CPF bili najvećeg prečnika od 20 do 110 mm (p=0,6744). Intenzitet peritumorskog limfoidnog odgovora je bio velik kod 13 tumora sa velikom gustinom TP/CPF (28,9%) i kod 17 tumora sa malom gustinom TP/CPF (24,6%), p=0,7747. Konfiguracija tumorske margine je bila infiltrativna u svim tumorima sa velikom gustinom TP/CPF, kao i kod 42 tumora sa malom gustinom TP/CPF (60,9%). ZAKLJUČAK: Velika gustina TP/CPF je nezavisan tkivni indikator lo&scaron;e prognoze kod bolesnika sa KK u stadijumu II, koji je ne korelira ni sa veličinom primarnog tumora ni sa intenzitetom peritumorskog limfoidnog odgovora. Velika gustina TP/CPF nije kompatibilna sa ekspanzivnom konfiguracijom tumorske margine, ali infiltrativna konfiguracija tumorske margine nije prediktor velike gustine TP/CPF.</p> / <p>INTRODUCTION: Colonic carcinoma (CC) is a serious public health problem due to its high incidence and mortality rate. Stage is the single most important independent prognosticator in patients with CC. In the presence of indicators of poor prognosis, including high histologic grade, ileus, lympho-vascular invasion and perineural invasion, there is a need for adjuvant chemotherapy after a potentially curative operation in patients with stage II CC, because the therapy improves both overall survival and disease-free survival. However, some patients with no documented poor prognostic factors suffer recurrences, which indicates that there may be some other tissue features that confer poor prognosis. In the recent publications there is an increasing interest in the phenomenon of tumor budding, a term assigned to the presence of small groups of discohesive tumor cells at the invasive front of the tumor &ndash; tumor buds (TB&#39;s). These cells acquire mesenchymal phenotype and gain the ability to migrate through the extracellular matrix by means of cytoplasmic extrusions which are visible on the two-dimensional immunohistologic sections and are called cytoplasmic pseudofragments (CPF&#39;s). Significance of density of TB&#39;s and CPF&#39;s is still to be evaluated, but the pool of evidence suggests that this is a powerful predictor of biologic behaviour of CC. AIM: The aim of this study was to determine the influence of density of TB&#39;s and CPF&#39;s on the risk of recurrence in patients with stage II CC. This research also attempted to establish whether there is a correlation between the density of TB&#39;s and CPF&#39;s and several other morphologic features such as tumor diameter, peritumoral lymphocytic response and the configuration of the tumor margin. METHODS: 114 patients with stage II CC were enrolled in the study. All the patients received surgery at the Institute of Oncology in Sremska Kamenica and no patient had indication for adjuvant chemotherapy. Microscopic analysis of routine histologic and immunohistochemical slides was performed to establish the density of TB&#39;s and CPF&#39;s, to estimate the intensity of the peritumoral lymphocytic response and to determine the configuration of the tumor margin. RESULTS: High density of TB&#39;s and/or CPF&#39;s was found in 45 tumors (39.5%). In this group recurrence occured in 26 patients (57.8%). In the group of patients with low density of TB/CPF in the tumor tissue 4 patients relapsed (5.8%). Comparison of survival curves showed that the probability of recurrence was significantly greater if the density of TB/CPF&#39;s was high (p&lt;0.0001). Tumors with high density of TB/CPF&#39;s ranged from 25 to 100 mm in greatest diameter, while those with low density measured from 20 to 110 mm (p=0.6744). Intensity of peritumoral lymphocytic response was high in 13 tumors with high density of TB/CPF&#39;s (28.9%) and in 17 tumors with low density of TB/CPF&#39;s (24.6%), p=0.7747. All tumors with high density of TB/CPF&#39;s and 42 tumors with low density of TB/CPF&#39;s (60.9%) had infiltrative configuration of tumor margin. CONCLUSION: High density of TB/CPF&#39;s is an independent indicator of poor prognosis in patients with stage II CC and it correlates neither with tumor diameter nor with intensity of peritumoral lymphocytic response. High density of TB/CPF&#39;s is not compatible with the expansive configuration of tumor margin, but the infiltrative configuration of tumor margin is not a predictor of high density of TB/CPF&#39;s.</p>

<p>Napredak na polju molekularne biologije omogućio je identifikaciju molekularnih markera za karcinom bronha sa vrednim prognostičkim i prediktivnim značajem i njihova uloga kod uznapredovalog, metastatskog oblika bolesti je u velikoj meri istražena, dok kod ranih stadijuma bolesti jo&scaron; uvek nije sasvim jasna. Cilj ovog istraživnja bio je da se utvrdi učestalost najče&scaron;ćih genskih alteracija u tumorskim ćelijama bolesnika sa ranim stadijumom adenokarcinoma bronha, da se utvrdi pojedinačna zavisnost ispitivanih genskih alteracija u tumorskim ćelijama sa određenim kliničko-patolo&scaron;kim karakteristikama i da se utvrdi potencijalni prognostički značaj pojedinačne genske alteracije u tumorskim ćelijama na vreme preživljavanja bez povratka bolesti i ukupno vreme preživljavanja. Istraživanje je obuhvatilo 161 bolesnika sa adenokarcinomom bronha, stadijuma bolesti od I do IIIA, kod kojih je sprovedena radikalna hirur&scaron;ka resekcija u Institutu za plućne bolesti Vojvodine u periodu izmedju 2007 i 2014 godine. U tumorskim uzorcima fiksiranim u parafinu odredjivane su mutacije EGFR, KRAS i PIK3CA gena, ALK i ROS1 rearanžman i PD1 i PD-L1 ekspresija. Kliničkopatolo&scaron;ke karakteristike su preuzete iz registra za karcinom bronha Instituta za plućne bolesti Vojvodine. Ukupno preživljavanje je računato od dana operacije do dana smrti, a preživljavanje bez povratka bolesti je računato od dana operacije do momenta ponovne pojave bolesti. Od 161 testiranog tumorskog uzorka, prisustvo mutacija detektovano je kod 96 uzoraka (59.6%). Prisustvo mutacije KRAS gena detektovano je kod 69 (42.9%), mutacije EGFR gena kod 10 (6.2%), a mutacije PIK3CA gena kod 7 (4.3%) tumorskih uzoraka. ALK rearanžman je detektovan kod 3 (1.9%), a ROS1 rearanžman kod 7 (4.3%) tumorskih uzoraka. PD-1 ekspresija detektovana je u 71 tumorskom uzorku (45%), dok je PD-L1 ekspresija detektovana u 59 tumorskih uzoraka (36.6%). PD-1 ekspresija nije bila značajno povezana ni sa jednim od klinčko-patolo&scaron;kih karakteristika (uključujući KRAS, EGFR, ALK, ROS1 i PI3KCA status). PD-L1 ekspresija je bila značajno povezana sa tipom hirurgije (P = 0.01) i sa prisustvom KRAS mutacije (P = 0.02). Mutacioni status u domenu KRAS gena je bio značajno povezan sa godinama starosti (P = 0.004), polom (P = 0.006) i pu&scaron;ačkim statusom (P = 0.004). Mutacioni status u domenu EGFR gena je bio značajno povezan sa pu&scaron;enjem (P &lt; 0.001) i sa godinama starosti (P = 0.013). Mutacioni statusi u domenu gena za ALK, ROS1 i PI3KCA nisu bili značajno povezani ni sa jednom od ispitivanih kliničko-patolo&scaron;kih karakteristika. Prisustvo PD-1 ekspresije je bilo značajno povezano sa preživljavanjem bez povratka bolesti (P = 0.03) i ukupnim preživljavanjem (P = 0.01). PD-L1 ekspresija, KRAS, EGFR, ALK, ROS1 i PIK3CA mutacioni status nisu bili značajno opvezani sa preživljavanjem bez povratka bolesti i ukupnim preživljavanjem. Najče&scaron;će detektovane genske alteracije su mutacije u domenu KRAS i EGFR gena. Prisustvo KRAS mutacije je značajno povezano sa godinama starosti ispitanika, polom i pu&scaron;ačkim statusom dok je prisustvo EGFR mutacije značajno povezano sa godinama starosti ispitanika i pu&scaron;ačkim statusom. Prisustvo PD-L1 ekspresije je značajno povezano sa vrstom hirur&scaron;kog lečenja i sa prisustvom KRAS mutacija. Jedino prisustvo PD-1 ekspresije u tumorskim ćelijama predstavlja nezavistan prognostički faktor za preživljavanje bez povratka bolesti i ukupno preživljavanje bolesnika sa ranim stadijumom adenokarcinoma bronha.</p> / <p>Advances in the field of molecular biology gave us insight into biomarkers for lung cancer with great prognostic and predictive value and their role in advanced stage disease is well known while in early stage disease is yet to be proven. The aim of this study was to determine the frequencies of the most common gene alterations in patients with early stage lung adenocarcinoma, to determine the relationship between gene alterations in tumor cells and clinicopathologial characteristics and to determine prognostic value of each gene alteration regarding overall survival and disease free survival. One hundred sixty-one patients diagnosed with lung adenocarcinoma clinical stage I-IIIA who underwent radical surgical resection at the Institute for Pulmonary Diseases of Vojvodina between 2007 and 2014 were included in this study. Mutations in EGFR, KRAS and PIK3CA gene, ALK and ROS1 rearrangement and PD-1 and PD-L1 expression were determined in representative formalin-fixed, paraffin-embedded (FFPE) tumor block from each patient. Clinical data were extracted from the institutional lung cancer registry of the Institute for Pulmonary Diseases. Overall survival was calculated as time from the day of surgery to the day of death. Disease free survival was calculated as time from the day of surgery to the day of disease relapse. Among 161 tested tumor tissue, presence of mutation was found in 96 (59.6%) of them. There were 69 (42.9%) mutations in KRAS gene, 10 (6.2%) in EGFR gene and 7 (4.3%) in PIK3CA gene. ALK and ROS1 rearrangement were present in 3 (1.9%) and 7 (4.3%), respectively. PD-1 expression was determined in 71 (45.0%) tumor sample while PD-L1 expression was determined in 59 (36.6%). PD-1 expression was not correlated with any of the clinicopathologial characteristics (including KRAS, EGFR, ALK, ROS1 and PIK3CA mutational status). PD-L1 expression correlated with type of surgery (P = 0.01) and KRAS positivity (P = 0.02). KRAS mutation status correlated with age (P = 0.004), sex (P = 0.006) and smoking status (P = 0.004). EGFR status correlated with smoking status (P &lt; 0.001) and age (P = 0.013). ALK, ROS1 and PIK3CA status were not correlated with any of the clinicopathologial characteristics. PD-1expression was significantly associated with disease free survival (P = 0.03) and overall survival (P = 0.01). PD-L1 expression, KRAS, EGFR, ALK, ROS1 and PIK3CA status were not associated with disease free survival and overall survival. The most frequent gene alteration are mutations in KRAS and EGFR gene. Presence of KRAS mutation is in correlation with patients age, sex and smoking status while presence of EGFR mutation is in correlation with patients age and smoking status. PD-L1 expression is in correlation with type of surgery and KRAS mutational status. Only presence of PD-1 expression represent an independent prognostic factor for disease free survival and overall survival.</p>