O Câncer de Esôfago é uma das neoplasias mais agressivas do trato gastrointestinal; é considerado como a nona neoplasia mais comum no mundo, além de ter altas taxas de mortalidade. A doença pode ser desencadeada por hábitos de vida, tais como etilismo e tabagismo, e também por fatores intrínsecos ao indivíduo. De todo modo, interfere significativamente em vários setores da vida do sujeito. Uma doença como o câncer pode conter uma tentativa simbólica para compensar uma atitude unilateral do indivíduo, ao relacionar-se com o ambiente e consigo mesmo. Acredita-se que conhecer aspectos do funcionamento e da dinâmica psíquica do sujeito pode contribuir para o foco do tratamento psicológico, de forma a propiciar intervenções psicológicas precoces e a auxiliar as demais equipes assistenciais nos cuidados e no modo de interação com o paciente. Entre elementos da estrutura psíquica do sujeito, buscou-se a tipologia psicológica dos referidos pacientes; para tanto, foi utilizado o Questionário de avaliação tipológica - QUATI (Zacharias, 2003). Além disso, valemo-nos de aspectos contidos na avaliação psicológica, rotina da instituição, com a finalidade de acessarmos as particularidades de cada um dos pacientes, especialmente no que se refere à reação ao diagnóstico e ao significado atribuído à doença. O estudo pode ser considerado como transversal, exploratório e descritivo. Foram incluídos 90 pacientes, derivados de análise estatística. Foram sujeitos da pesquisa pacientes maiores de 18 anos com diagnóstico de câncer de esôfago; com ensino fundamental completo; virgens de tratamento; atendidos em primeira consulta, no ambulatório de cirurgia do aparelho digestivo, do Instituto do Câncer do Estado de São Paulo (ICESP-HCFMUSP). Encontramos esses pacientes em sala de espera da consulta médica, onde foram informados sobre o objetivo da pesquisa; e, àqueles que aceitaram participar, foi aplicado o termo de consentimento livre e esclarecido, seguido da avaliação psicológica (rotina da instituição) e aplicação do instrumento. Os resultados indicaram que a maior parte da nossa amostra tem uma atitude introvertida. O tipo psicológico mais comum foi o introvertido sensação, com função auxiliar sentimento. A partir da avaliação psicológica, constatou-se uma variedade de mecanismos defensivos para minimização da angústia. A grande parte dos pacientes valeu-se de defesas adaptativas diante do processo de adoecimento. Conclui-se que, no atendimento com esses pacientes, torna-se necessária uma postura prática e objetiva dos profissionais de saúde, em que se busque fornecer orientações com base na realidade dos pacientes, assim como ter um modo de agir empático, com o estabelecimento de vínculo significativo, mas respeitando os limites dos pacientes, sobretudo ao que se refere à forma reservada e introspectiva de interagirem com o mundo e com as pessoas que os cercam / Esophageal cancer is one of the most aggressive neoplasms of the gastrointestinal tract, and can be triggered by life habits such as alcoholism and smoking and factors intrinsic to the individual. A disease such as cancer can hold a symbolic attempt to compensate for a onesided attitude of the individual. It is believed that knowing aspects of the psychic dynamics of the person, can contribute to the focus of a psychological treatment, in order to provide early psychological interventions, as well as assisting other attending teams in the care of and interaction with the patient. Among the psychic structure elements of a subject, we looked for the psychological typology of these patients. Typological Assessment Questionnaire was used to evaluate the psychological typology. In addition, we drew on aspects from within the psychological assessment, routine of the institution, in order to access the particularities of each one of the patients, especially concerning their reaction to the diagnosis and the meaning attributed to the disease. Ninety patients were included. They were over 18 years old, having completed middle-school education, diagnosed with esophageal cancer, and interviewed during their first medical appointment at the Digestive Surgery Clinic at the Cancer Institute of the State of São Paulo (ICESP-HCFMUSP). We met these patients in the waiting room, where they were informed of the purpose of the survey. Those who agreed to participate, were given the terms of free and informed consent, followed by a psychological evaluation and the application of the instrument used. The results indicated a predominant introverted attitude. The most common psychological type was the introverted feeling, with feeling as a secondary function. From this psychological evaluation, we found a variety of defensive mechanisms to minimize the anguish. Most of the patients made use of adaptive defenses when facing the illness process. Therefore, when attending these patients, health professionals must have a practical and objective posture, seeking to guide the patients according to their reality. In addition, they should be empathetic in their manner, establishing significant bond, but respecting the patients\' limits, especially when it comes to their reserved and introspective way of interacting with the world and the people around them

Wang, Yajun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 118-126). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Figures --- p.xi / List of Tables --- p.xii / Abbreviations and Symbols --- p.xiii / List of Publications and Sequence Submissions during the Study --- p.xv / Chapter Chapter One: --- General Introduction --- p.1 / Chapter Chapter Two: --- Literature Review --- p.8 / Chapter 2.1 --- DNA methylation --- p.8 / Chapter 2.1.1 --- Epigenetic changes --- p.8 / Chapter 2.1.2 --- Differential methylation pattern in normal and tumor cells --- p.10 / Chapter 2.2 --- TSGs --- p.13 / Chapter 2.2.1 --- "Cancer initiation, progression and cancer genes" --- p.13 / Chapter 2.2.2 --- TSGs could be inactivated through promoter hypermethylation --- p.14 / Chapter 2.3 --- NPC --- p.17 / Chapter 2.3.1 --- Epidemiology ofNPC --- p.18 / Chapter 2.3.2 --- Molecular genetic and epigenetic studies ofNPC --- p.19 / Chapter 2.3.3 --- NPC and chromosome 11q --- p.21 / Chapter 2.4 --- ESCC --- p.21 / Chapter 2.4.1 --- Epidemiology of ESCC --- p.22 / Chapter 2.4.2 --- Genetic and epigenetic studies of ESCC --- p.23 / Chapter 2.4.3 --- ESCC and chromosome 11q --- p.24 / Chapter 2.5 --- Chromosome 11q and other carcinomas --- p.24 / Chapter 2.5.1 --- Breast cancer --- p.24 / Chapter 2.5.2 --- Ovarian cancer --- p.25 / Chapter 2.5.3 --- Neuroblastoma --- p.26 / Chapter 2.5.4 --- Melanoma --- p.27 / Chapter 2.5.5 --- Multiple myeloma --- p.27 / Chapter 2.5.6 --- Lung Cancer --- p.27 / Chapter 2.6 --- Important candidate genes located at the project study 1 lq region --- p.28 / Chapter 2.6.1 --- ETS1 --- p.28 / Chapter 2.6.2 --- FLI1 --- p.29 / Chapter 2.6.3 --- P53AIP1 --- p.30 / Chapter 2.6.4 --- RICS --- p.30 / Chapter 2.6.5 --- BARX2 --- p.30 / Chapter 2.6.6 --- ST14 --- p.32 / Chapter 2.6.7 --- ADAMTS8 --- p.33 / Chapter 2.6.8 --- ADAMTS15 --- p.35 / Chapter 2.6.9 --- HNT --- p.36 / Chapter 2.6.10 --- OPCML --- p.36 / Chapter Chapter Three: --- Materials and Methods --- p.37 / Chapter 3.1 --- Cell lines and primary tumor samples --- p.37 / Chapter 3.2 --- Cell line demethylation treatment --- p.38 / Chapter 3.3 --- DNA and RNA extraction from cell lines and tissues --- p.39 / Chapter 3.4 --- Semiquantitative RT-PCR --- p.41 / Chapter 3.5 --- DNA bisulfite treatment --- p.42 / Chapter 3.6 --- Promoter analysis and identification of 5' CpG islands of target genes --- p.45 / Chapter 3.7 --- Methylation-Specific PCR (MSP) --- p.45 / Chapter 3.8 --- Bisulfite Genomic Sequencing (BGS) --- p.46 / Chapter 3.8.1 --- BGS PCR reaction --- p.46 / Chapter 3.8.2 --- TA cloning of the PCR products into the sequencing vector --- p.47 / Chapter 3.8.3 --- Plasmid mini-preparation on 96-well plate --- p.48 / Chapter 3.8.4 --- Plasmid sequencing --- p.49 / Chapter 3.9 --- Homozygous deletion detection --- p.50 / Chapter 3.10 --- Construction of expression plasmids --- p.51 / Chapter 3.10.1 --- The strategy of full length cDNA cloning --- p.51 / Chapter 3.10.2 --- Obtaining of full length covered cDNA by cloning PCR --- p.53 / Chapter 3.10.3 --- Ligation and transformation --- p.54 / Chapter 3.10.4 --- Mini preparation of plasmid in Eppendorf tubes --- p.54 / Chapter 3.10.5 --- Verification of correct inserts in the plasmid --- p.55 / Chapter 3.10.6 --- Subcloning --- p.55 / Chapter 3.10.7 --- Bacteria storage --- p.57 / Chapter 3.11 --- Colony formation assays (CFA) --- p.57 / Chapter 3.11.1 --- Midiprep of the transfection grade plasmid --- p.57 / Chapter 3.11.2 --- Transfection --- p.58 / Chapter 3.11.3 --- Selection of the transfected cells with G418 --- p.59 / Chapter 3.11.4 --- Colony staining --- p.60 / Chapter 3.12 --- Statistical analysis --- p.60 / Chapter Chapter Four: --- Results --- p.61 / Chapter 4.1 --- Narrow down the candidate genes for further study --- p.61 / Chapter 4.1.1 --- Define the study chromosome region --- p.61 / Chapter 4.1.2 --- Database search of all candidate genes --- p.61 / Chapter 4.1.3 --- Transcriptional expression analysis of the candidate genes --- p.63 / Chapter 4.1.4 --- Selection of the genes with tumor specific expression downregulation for further intensive study --- p.64 / Chapter 4.2 --- Further characterization of ADAMTS8 --- p.69 / Chapter 4.2.1 --- Tissue transcriptional expression panel --- p.69 / Chapter 4.2.2 --- Semiquantitative RT-PCR results in tumor cell lines --- p.70 / Chapter 4.2.3 --- Promoter CpG island identification and promoter methylation study --- p.70 / Chapter 4.2.4 --- Transcription reactivation by demethylation treatment --- p.72 / Chapter 4.2.5 --- High resolution promoter methylation analysis by BGS --- p.72 / Chapter 4.2.6 --- Detection of homozygous deletion --- p.73 / Chapter 4.2.7 --- Analysis of ADAMTS8 promoter methylation in clinical samples --- p.74 / Chapter 4.2.8 --- ADAMTS8 full length cDNA cloning --- p.74 / Chapter 4.2.9 --- Colony formation assay --- p.75 / Chapter 4.3 --- Further characterization of HNT --- p.80 / Chapter 4.3.1 --- Tissue transcriptional expression panel --- p.80 / Chapter 4.3.2 --- Semiquantitative RT-PCR results in tumor cell lines --- p.80 / Chapter 4.3.3 --- Promoter CpG island identification and promoter methylation study --- p.81 / Chapter 4.3.4 --- Transcription reactivation by demethylation treatment --- p.82 / Chapter 4.3.5 --- HNT full length cDNA cloning --- p.82 / Chapter 4.4 --- Further characterization of BARX2 --- p.87 / Chapter 4.4.1 --- Tissue transcriptional expression panel --- p.87 / Chapter 4.4.2 --- Semiquantitative RT-PCR results in tumor cell lines --- p.87 / Chapter 4.4.3 --- Promoter CpG island identification and promoter methylation study --- p.88 / Chapter 4.4.4 --- Transcription reactivation by demethylation treatment --- p.89 / Chapter 4.4.5 --- BARX2 full length cDNA cloning --- p.89 / Chapter 4.5 --- Further study of other downregulated genes --- p.92 / Chapter 4.5.1 --- FLII --- p.92 / Chapter 4.5.2 --- ADAMTS15 --- p.94 / Chapter 4.5.3 --- P53AIP1 --- p.97 / Chapter Chapter Five: --- Discussion --- p.100 / Reference List --- p.118 / Appendix I: Reagents Preparation Recipe --- p.127 / Appendix II: PCR Primers for cDNA Cloning --- p.129

Yu, Le. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 171-198). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

In brief, mRNA expression profiling of candidate genes in each locus was performed using semi-quantitative RT-PCR in a panel of ESCC and NPC cell lines, normal tissues and immortalized epithelial cell lines. Genes downregulated in cancer cells but with high expression in normal tissues and immortalized epithelial cells were subjected to promoter methylation analysis using methylation-specific PCR (MSP), bisulfite genomic sequencing (BGS) and pharmacological demethylation treatment. Genes with tumor-specific downregulation and methylation were further selected as candidates and their tumor suppressive roles were verified via functional studies. / In conclusion, RAB39 and WDRX, epigenetically silenced in multiple cancer cell lines, were identified as novel TSG candidates in this study. Meanwhile, the tumor suppressive functions of ADAMTS8 were further validated, proving the efficiency of this integrative approach. Further study on these novel TSG candidates may help to elucidate the detailed molecular mechanisms for ESCC and NPC, and provide novel therapeutic targets and biomarkers. / In this study, RAB39 and WDRX were identified as candidate TSGs in 11q22.3 and 15q21.3, respectively. Both genes were broadly expressed in normal tissues and immortalized epithelial cell lines, but significantly downregulated and methylated in multiple cancer cell lines. Demethylation treatment with 5-Aza-2'-deoxycytidine restored their mRNA expression, indicating that CpG methylation directly contributed to their transcriptional inactivation. Methylation of RAB39 and WDRX was detected in primary ESCC and NPC, but rarely observed in normal tissues, implicating that their tumor-specific methylation might be used as biomarkers. Ectopic expression of both genes significantly inhibited the clonogenicity of multiple cancer cell lines, supporting their potential roles as functional TSGs. Moreover, WDRX repressed WNT/beta-catenin signaling, underscoring a possible anti-tumorigenic mechanism for it. In addition, ADAMTS8 was revealed to inhibit clonogenicity of NPC and ESCC cell lines, acting as a negative modulator for ERK pathway and a potential pro-apoptotic metalloprotease. / Inactivation of tumor suppressor genes (TSGs) contributes to the genesis of cancers including esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC), two prevalent causes of death in Hong Kong. Apart from genetic abnormalities, epigenetic disruptions including CpG methylation represent another major mechanism for TSG inactivation. Promoter methylation of multiple TSGs was detected in different cancer types, suggesting that it could be utilized as therapeutic target or biomarker for disease diagnosis and prognosis. / TSGs are often located at frequently deleted chromosomal regions and subjected to tumor-specific methylation, making it possible to use an integrative epigenetic and genomic approach combining array comparative genomic hybridization (aCGH) with epigenetic profiling to screen for novel TSGs. Previous aCGH revealed that several loci in 11822.3, 15q14, 15q21.1 and 15q21.3 underwent frequent copy number loss in ESCC cell lines. Loss of heterozygosity (LOH) of these regions was also reported in other cancers, indicating that TSGs might reside within them. The aim of this study was thus to identify the candidate TSGs in these loci and study their anti-tumorigenic roles. In addition, the tumor suppressive function of ADAMTS8, a silenced 11q25 candidate TSG previously identified in our lab via this approach, was also studied. / Li, Jisheng. / Adviser: Qian Tao. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 136-159). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 44-53).

O Câncer de Esôfago é uma das neoplasias mais agressivas do trato gastrointestinal; é considerado como a nona neoplasia mais comum no mundo, além de ter altas taxas de mortalidade. A doença pode ser desencadeada por hábitos de vida, tais como etilismo e tabagismo, e também por fatores intrínsecos ao indivíduo. De todo modo, interfere significativamente em vários setores da vida do sujeito. Uma doença como o câncer pode conter uma tentativa simbólica para compensar uma atitude unilateral do indivíduo, ao relacionar-se com o ambiente e consigo mesmo. Acredita-se que conhecer aspectos do funcionamento e da dinâmica psíquica do sujeito pode contribuir para o foco do tratamento psicológico, de forma a propiciar intervenções psicológicas precoces e a auxiliar as demais equipes assistenciais nos cuidados e no modo de interação com o paciente. Entre elementos da estrutura psíquica do sujeito, buscou-se a tipologia psicológica dos referidos pacientes; para tanto, foi utilizado o Questionário de avaliação tipológica - QUATI (Zacharias, 2003). Além disso, valemo-nos de aspectos contidos na avaliação psicológica, rotina da instituição, com a finalidade de acessarmos as particularidades de cada um dos pacientes, especialmente no que se refere à reação ao diagnóstico e ao significado atribuído à doença. O estudo pode ser considerado como transversal, exploratório e descritivo. Foram incluídos 90 pacientes, derivados de análise estatística. Foram sujeitos da pesquisa pacientes maiores de 18 anos com diagnóstico de câncer de esôfago; com ensino fundamental completo; virgens de tratamento; atendidos em primeira consulta, no ambulatório de cirurgia do aparelho digestivo, do Instituto do Câncer do Estado de São Paulo (ICESP-HCFMUSP). Encontramos esses pacientes em sala de espera da consulta médica, onde foram informados sobre o objetivo da pesquisa; e, àqueles que aceitaram participar, foi aplicado o termo de consentimento livre e esclarecido, seguido da avaliação psicológica (rotina da instituição) e aplicação do instrumento. Os resultados indicaram que a maior parte da nossa amostra tem uma atitude introvertida. O tipo psicológico mais comum foi o introvertido sensação, com função auxiliar sentimento. A partir da avaliação psicológica, constatou-se uma variedade de mecanismos defensivos para minimização da angústia. A grande parte dos pacientes valeu-se de defesas adaptativas diante do processo de adoecimento. Conclui-se que, no atendimento com esses pacientes, torna-se necessária uma postura prática e objetiva dos profissionais de saúde, em que se busque fornecer orientações com base na realidade dos pacientes, assim como ter um modo de agir empático, com o estabelecimento de vínculo significativo, mas respeitando os limites dos pacientes, sobretudo ao que se refere à forma reservada e introspectiva de interagirem com o mundo e com as pessoas que os cercam / Esophageal cancer is one of the most aggressive neoplasms of the gastrointestinal tract, and can be triggered by life habits such as alcoholism and smoking and factors intrinsic to the individual. A disease such as cancer can hold a symbolic attempt to compensate for a onesided attitude of the individual. It is believed that knowing aspects of the psychic dynamics of the person, can contribute to the focus of a psychological treatment, in order to provide early psychological interventions, as well as assisting other attending teams in the care of and interaction with the patient. Among the psychic structure elements of a subject, we looked for the psychological typology of these patients. Typological Assessment Questionnaire was used to evaluate the psychological typology. In addition, we drew on aspects from within the psychological assessment, routine of the institution, in order to access the particularities of each one of the patients, especially concerning their reaction to the diagnosis and the meaning attributed to the disease. Ninety patients were included. They were over 18 years old, having completed middle-school education, diagnosed with esophageal cancer, and interviewed during their first medical appointment at the Digestive Surgery Clinic at the Cancer Institute of the State of São Paulo (ICESP-HCFMUSP). We met these patients in the waiting room, where they were informed of the purpose of the survey. Those who agreed to participate, were given the terms of free and informed consent, followed by a psychological evaluation and the application of the instrument used. The results indicated a predominant introverted attitude. The most common psychological type was the introverted feeling, with feeling as a secondary function. From this psychological evaluation, we found a variety of defensive mechanisms to minimize the anguish. Most of the patients made use of adaptive defenses when facing the illness process. Therefore, when attending these patients, health professionals must have a practical and objective posture, seeking to guide the patients according to their reality. In addition, they should be empathetic in their manner, establishing significant bond, but respecting the patients\' limits, especially when it comes to their reserved and introspective way of interacting with the world and the people around them

Introdução: Narrow-Band Imaging (NBI) é uma das mais recentes técnicas de processamento de imagem, que consiste na utilização de filtros para dissociação das bandas do espectro da luz, resultando em aumento de contraste da superfície epitelial e da vascularização. Em combinação com a magnificação de imagem, pode-se diferenciar os tipos epiteliais e identificar áreas de padrão vascular decorrente de processos inflamatórios ou de neoplasias superficiais. A utilização da endoscopia associada à cromoscopia com solução de Lugol já é método consagrado na detecção de lesões superficiais em pacientes de alto risco, sendo largamente utilizado na prática diária. Objetivo: avaliar a aplicabilidade clínica da técnica de NBI na detecção e avaliação de neoplasias de esôfago em pacientes portadores de estenose do esôfago por agente corrosivo, comparando-a com a cromoscopia com solução de Lugol. Pacientes e Métodos: foram submetidos à avaliação com NBI 38 pacientes, sendo 22 e 16, com idade entre 28 84a (média M 56). O equipamento empregado é da linha de processadora Olympus, série EVIS II 180, Gastroscópio Olympus, série 180 GIF Type N180 slimsight ,com diâmetro 4.9mm, propiciando conforto ao paciente, sem a necessidade de dilatação da estenose. O exame iniciava-se com a remoção de resíduos e secreções do esôfago com irrigação vigorosa de soro fisiológico e N-acetil cisteína; após avaliação completa e constatando-se a ausência de lesões detectáveis sem auxílio de cromoscopia, era realizada a avaliação por meio por meio da técnica do NBI e cromoscopia com solução de Lugol, seguido de biópsia dirigida das eventuais lesões ou do anel estenótico. Resultados: lesões suspeitas pelo NBI totalizaram 9, e pelo teste de Lugol, (14), evidenciando uma sensibilidade e especificidade para o teste do NBI de 100% e 80.56% respectivamente; e a mesma relação de 100% e 66.67%, para o teste com a solução de Lugol 5 (13%) lesões suspeitas apresentaram-se positivas pelo NBI e pelo Lugol; destas, 2 (40%) foram confirmadas no anatomopatológico como carcinoma. Discussão: o NBI aumenta o contraste entre os vasos e a mucosa. Os vasos aparecem de cor marrom escura e a mucosa, azul claro. No exame normal os padrões vasculares e de mucosa são regulares e bem distribuídos. Se qualquer crescimento anormal ocorre (inflamatório, displásico ou neoplásico) a imagem muda, se torna mais escura (marrom), destacando-se da superfície azulada da mucosa. Com a ajuda da magnificação de imagem a identificação de possíveis lesões suspeitas se torna mais fácil. Esses achados determinam o local mais adequado para biópsia, aumentando as chances de diagnóstico de lesões displásicas e neoplásicas. Esse estudo revelou que a mucosa esofágica após lesão cáustica se torna esbranquiçada com pequenos pontilhados azulados, quando examinada com a técnica de NBI. Conclusão: o emprego da técnica de cromoscopia óptica (NBI) surge como opção na avaliação da estenose do esôfago por ingestão de agente corrosivo, para pesquisa de tumor. / Introduction: The Narrow Band Imaging system is a new method of endoscopic imaging. It´s based in the use of optical filters to dissociate bands of light spectrum, emphasizing certain live imaging features such as capillary and mucosal patterns. The upper GI endoscopy associated with Lugol´s solution chromoscopy is a well know method for detecting superficial lesions in high risk patients. Objetive: determinate the clinical applicability of the NBI technique for detection of esophagus cancer in patients with caustic lesion/corrosive agent stenosis and compare it to Lugol´s solution chromoscopy. Patients and Methods: 38 patients ( 22 female and 16 male ), aging between 28-84 (M 56) were enrolled to this study and examined by both NBI technique and Lugol´s solution chromoscopy. The instrument used in this study was a Olympus EVIS II-180, slimsight, with 4,9mm diameter, promoting the exam of the stenotic ring or segment without the need of dilation. The exam started with the removal of esophageal residues with N-Acetilcystein and physiologic solution. Followed the full routine exam of the esophagus. Next, the NBI was performed and any lesion detected was marked for later biopsy. After that, the Lugol´s solution crhomoscopy was performed and biopsies were taken if necessary. Patients who had normal findings at the routine, NBI or Lugol´s solution chromoscopy exam had their stenotic ring biopsed. Results: suspicious lesions with NBI were 9, and with the Lugol\'s chromoscopy 14. The sensibility and specificity of the NBI was 100% and 80.56%, and of the Lugol´s chromoscopy 100% and 66.67%, respectively. 5 (13%) suspicious lesions were detected both with NBI and Lugol\'s chropmoscopy, 2 (40%) of these lesions were confirmed carcinoma in the anatomopatholic exam. Discussion: the advantage of the NBI is enhance the contrast between vessels and the mucosa. The vessels appear as dark-brownish lines and the mucosa as light brownish color. In a normal exam, the vascular and mucosal patterns are regular and well distributed. If any abnormal growth takes place (inflammatory, displasic or neoplasic) the image changes into areas of darker brownish color and with the help of magnification, irregular or distorced vascular or mucosal pattern can be identified. These findings guide the exact site to be biopsed, increasing the chances of detecting possible displasic or neoplasic lesions. This study observed that the esophageal mucosa previously injured by corrosive agents had a whitish color, spoted by light blue areas, when examined with NBI technique. Conclusion: the NBI system is an option applicable to detect and evaluate cancer in patients with caustic lesion/corrosive stenosis compared to the Lugol´s solution chromoscopy.

Orientador: Luiz Roberto Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T19:36:32Z (GMT). No. of bitstreams: 1 Bianchi_RenataCristianeGennari_D.pdf: 1264896 bytes, checksum: e7f0d2b827693233f95ddfd5a5e1ab93 (MD5) Previous issue date: 2012 / Resumo: As neoplasias esofágicas passíveis de tratamento por radioterapia podem induzir seqüelas clínicas importantes como a pneumonite radioinduzida e a fibrose pulmonar. É sabido que os exercícios físicos promovem uma seqüência de liberação de citocinas pró-inflamatórias, com diminuição dos efeitos deletérios das desordens cardiovasculares e promoção de efeito protetor contra as doenças associadas à inflamação sistêmica. Diante deste fato, o presente estudo teve o objetivo de verificar se a atividade física pré-radioterapia possui elementos radioprotetores, medindo-se a ativação de citocinas pró-inflamatórias como a interleucina-6 (IL-6), fator transformador de crescimento-bete (TGF-'beta'), fator de necrose tumoral-alfa (TNF-'alfa') e quinase de proteína beta (IKK'beta'), por meio da análise de Western Blotting (WB). Para isto, foi realizado um estudo randomizado empregando 28 ratos Wistar Hannover, machos, com idade média de 90 dias e e peso aproximado de 200 gramas. Os animais foram divididos em 3 grupos. Gl (grupo controle), Gll (grupo que foi submetido à radioterapia e sacrificado no 1o dia pós-radioterapia - Glla ou sacrificado no 7o dia pós-radioterapia - Gllb) e Glll (grupo que realizou atividade física e radioterapia e foi sacrificado no 1°dia pós-radioterapia- Gllla ou sacrificado no 7°dia pós-radioterapia- Glllb). A atividade física do grupo Glll consistiu em natação, durante 8 semanas (carga zero, 3 vezes por semana, cerca de 30 minutos). Após tal atividade física, Gll e Glll foram submetidos à irradiação por cobaltoterapia, dose única de 3,5 grays em corpo inteiro. Todos os animais foram sacrificados por overdose de pentobarbital, de acordo com o tempo de análise de citocinas, e em seguida, um fragmento do lobo inferior do pulmão direito foi foi analisado por WB. Como resultado, a expressão das citocinas IKK'beta', TNF-'alfa' e IL-6 induzidas por radiação no pulmão foi menor nos animais que se exercitaram e que foram sacrificados no 7°dia pós-radioterapia (Glllb), com significância estatística através do teste de ANOVA (p<0,05). No entanto, o exercício não alterou o aumento induzido pela radiação em relação à TGF-'beta'. Concluiu-se que a atividade física possui elementos radioprotetores, pois houve menor aumento de IKK'beta', TNF-'alfa' e IL-6 nos grupos pós-atividade física (Glllb), com sugestão de menor inflamação e lesão tecidual pós-radioterapia. Possivelmente não houve significância estatística em relação à TGF-'beta', pois tal citocina tem papel preponderante numa fase mais tardia de injúria tecidual, ou seja, na fibrose pulmonar. Além disso, as citocinas analisadas mostraram-se bons marcadores para mensurar a resposta inflamatória tecidual pulmonar / Abstract: Esophageal neoplasms amenable to treatment by radiation therapy may induce important clinical radioinduced sequelae as pneumonitis and pulmonary fibrosis. It is known that exercise promotes a sequence of release of proinflammatory cytokines, decreasing the deleterious effects of cardiovascular disorders and promotion of protective effect against diseases associated with systemic inflammation. Given this fact, this study aimed to determine whether physical activity pre-radiotherapy has radioprotective elements by measuring the activation of proinflammatory cytokines such as interleukin-6 (IL-6), transforming growth factor-beta (TGF-'beta'), tumor necrosis factor-alpha (TNF-'alpha') and beta protein kinase (IKK'beta') by means of Western Blotting (WB) analysis. For this, we performed a randomized study using 28 male Wistar Hannover rats, males with a mean age of 90 days and and weighing approximately 200 grams. The animals were divided into 3 groups. Gl (control group), Gil (group underwent radiotherapy and sacrificed on day 1 after radiation therapy - Gila or sacrificed on day 7 post-radiotherapy -Glib) and GIN (the group that performed physical activity and radiotherapy and was sacrificed on day 1 post-radiotherapy-Gllla or sacrificed on day 7 post-radiotherapy-Glllb). The physical activity of the group GIN consisted of swimming for 8 weeks (zero load, three times per week, about 30 minutes). After this activity, Gil and GIN were subjected to irradiation by cobalt, a single dose of 3.5 Gy of whole body. All animals were sacrificed by an overdose of pentobarbital, according to the analysis time of cytokines, and then a fragment of the lower lobe of right lung was analyzed by WB. As a result, the expression of cytokines IKK 'beta', TNF-'alpha' and IL-6 induced by radiation in the lungs was lower in the exercised animals and that were sacrificed on day 7 post-radiotherapy (Glllb), with statistical significance by ANOVA test (p<0,05) . However, the exercise did not affect the increase induced by radiation in relation to TGF-'beta'. It was concluded that physical activity has radioprotective elements because there was a lower increase of IKK 'beta', TNF-'alpha' and IL-6 in post-exercise groups (Glllb), with suggestion of less inflammation and tissue injury after radiation therapy. Possibly there was no statistical significance in relation to TGF-'beta', as this cytokine plays an important role in a later phase of tissue injury, namely pulmonary fibrosis. Furthermore, the cytokines analyzed proved to be good markers to measure the pulmonary inflammatory response / Doutorado / Fisiopatologia Cirúrgica / Doutor em Ciências

O carcinoma espinocelular é o principal tipo histológico de neoplasia esofágica, com o pico de incidência ocorrendo na 6ª década de vida, o que sugere a ação prolongada de agente(s) carcinogênico(s) do ambiente externo como fator etiológico. A associação entre câncer de cabeça e pescoço e esôfago é conhecida de longa data, ocorrendo em 2 a 36% dos pacientes, com risco relativo 10 a 30 vezes maior comparado ao da população em geral. Uma das hipóteses sobre a ocorrência de tumores malignos múltiplos baseia-se na teoria da cancerização de área (field cancerization) descrita por Slaughter et al. em 1953, a qual explica a ação de fatores causais atuando em conjunto sobre o trato aerodigestivo e originando a carcinogênese. No Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brasil, foi realizado um estudo retrospectivo com a finalidade de examinar pacientes portadores de neoplasia primária de cabeça e pescoço quanto a: prevalência de câncer esofágico, consumo de etanol, tabaco e hábitos alimentares como fatores de risco. No período de dezembro de 1995 a outubro de 2000, 326 pacientes com neoplasia primária de cabeça e pescoço foram avaliados clínica e endoscopicamente com auxílio de corante (cromoendoscopia com lugol). Foram detectados 36 casos de câncer esofágico (prevalência: 11,04%) e nos pacientes que desenvolveram segunda neoplasia maligna do esôfago, os seguintes fatores foram relevantes: idade precoce de início do consumo de etanol (p<0,05), maior duração e consumo semanal de etanol (p<0,05). Não se observou um risco maior de incidência de câncer de esôfago em relação ao consumo de tabaco isoladamente (p>0,05), porém, o consumo conjunto de tabaco e etanol foi relacionado a um risco maior de neoplasia de esôfago (p<0,05). Não foi demonstrada associação entre hábitos alimentares e a presença de um segundo tumor maligno de esôfago. / Spinocellular carcinoma is the predominant histological type of esophageal cancer with its peak incidence in the sixth decade of life, which suggests the long-term action of external carcinogenic agents as an etiologic factor. The association between head and neck cancer and esophageal cancer has long been known, occurring in 2 to 36% of the patients, with a relative risk 10 to 30 times higher compared to that of the general population. One of the hypothesis on the occurrence of multiple malignant tumors is based on the \"field cancerization\" theory described by Slaughter et al. in 1953. It explains the combined action of causal factors on the aerodigestive tract which leads to carcinogenesis. A retrospective study was conducted in Hospital das Clinicas of the Medical School of the University of São Paulo, Brazil, aiming at investigating patients with head and neck primary tumors for: the predominance of esophageal cancer, ethanol consumption, tobacco smoking and dietary habits as risk factors. From December 1995 to October 2000, 326 patients with primary head and neck tumors were clinically and endoscopically assessed with the use of Lugol\'s dye chromoendoscopy. 36 cases of esophageal cancer were detected (prevalence:11,04%) and in those patients that developed a second malignant tumor in the esophagus the following factors were relevant: ethanol consumption beginning at adolescence (p<0,05), longer duration of drinking habit and weekly consumption of ethanol (p<0,05). No increased risk of esophageal cancer was found associated with tobacco smoking alone (p>0,05), however, combined alcohol and tobacco consumption was found to increase the risk of esophageal cancer (p<0,05). No association was found between dietary habits and the presence of a second malignant tumor of the esophagus.

Introdução: O câncer de esôfago (CaE) ocorre em 22% dos casos como doença local, e a minoria dessa doença é limitada à mucosa ou à submucosa (lesões precoces). Ressecção endoscópica da mucosa (EMR), dissecção submucosa endoscópica (ESD), terapia fotodinâmica (PDT), terapia a laser e coagulação com plasma de argônio (APC) têm sido desenvolvidas como alternativas à ressecção cirúrgica de lesões precoces. Objetivos: Identificar, por meio de revisão sistemática, estudos que reportem sobrevida, sobrevida livre de doença, morbidade e mortalidade associada ao procedimento e mortalidade associada ao câncer em terapias endoscópicas e cirúrgicas no câncer de esôfago limitado à mucosa ou à submucosa (lesões precoces). Fontes de dados: Uma revisão sistemática de artigos em MEDLINE, Registro Cochrane de Ensaios Clínicos Controlados, EMBASE, EBSCO, LILACS, Biblioteca da Universidade de São Paulo e em sites de pesquisa, como BVS e SCOPE ScienceDirect. Seleção do estudo: Ensaio Controlado Aleatório, Ensaio Clínico Controlado, Ensaio Clínico e Estudos de Coorte. Critérios de seleção: Estudos que comparam estatisticamente a sobrevida e a sobrevida livre de doença, a morbidade e a mortalidade associada ao procedimento e a mortalidade associada ao câncer no tratamento endoscópico e cirúrgico para lesões precoces do câncer de esôfago. Extração de dados: Extração independente de dados de artigos por dois autores, incluindo os indicadores de qualidade dos estudos. Na busca, não foi encontrado nenhum tipo de ensaio clínico; portanto, extraímos apenas estudos comparativos retrospectivos e os resultados extraídos forma analisados estatisticamente. Limitação: Apenas estudos prospectivos, comparando as terapias endoscópicas e cirúrgicas, bem como as terapias reportadas com heterogeneidade. Resultados: Em estudos comparando as terapias cirúrgica e endoscópica na mortalidade relacionada ao procedimento, a diferença não foi significativa; nas taxas de sobrevivência após 1, 2, 3, 4 e 5 anos, foram diferentes e mostraram superioridade da cirurgia ao longo do tempo, estas foram aparentemente influenciadas por vieses na população. Ao suprimir esse viés, a endoscopia é superior no controle da mortalidade relacionada ao câncer com alta taxa de recidiva da doença. Em relação à comorbidade e à mortalidade associada ao procedimento, a endoscopia apresenta melhores resultados. Conclusões e implicações: Não existem evidências reportadas de ensaios clínicos. Nesta metanálise, as terapias cirúrgicas mostraram superioridade na sobrevida, e as terapias endoscópicas apresentaram superioridade no controle da mortalidade relacionada ao câncer, mas com alta taxa de recorrência da doença, a comorbidade e a mortalidade associadas à endoscopia é menor. Ensaios controlados com volume amostral expressivo são necessários para confirmar os resultados da metanálise atual. Número de registro de revisão sistemática: CRD42014013170 / Esophageal cancer occurs in 22% of cases as a local disease, and a minority of this disease is limited to mucosa or submucosa (early lesions). Endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), photodynamic therapy (PDT), laser therapy, and argon plasma coagulation (APC) have been developed as alternatives to surgical resection for early lesions. Objectives: The aim of this systematic review is to identify studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated to cancer in the endoscopic and surgical therapies. Data sources: A systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register, EMBASE, EBSCO, LILACS, Library University of São Paulo, Research websites BVS and SCOPE ScienceDirect. Study selection: Randomized Controlled Trial, Controlled Clinical Trial, Clinical Trial and Cohort Study. Criteria: Studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated to cancer in the endoscopic and surgical therapies for early lesions of esophageal cancer. Data extraction: Independent extraction of articles by two authors using predefined data fields, including study quality indicators. In the search, I did not find any type of clinical trial; therefore, I extracted only retrospective comparative studies and analyzed statistically the results extracted. Limitation: Only prospective studies comparing the endoscopy and surgery therapies with heterogeneity. Results: Studies comparing surgical and endoscopic therapies showed in the procedure-related mortality, the difference was not significant; in the survival rates after 1, 2, 3, 4 and 5 years were different and showed superiority of surgical therapies over time, these were apparently influenced by biases in selection of population, when this bias is removed, endoscopy is superior in control of mortality related to cancer with a high rate of disease recurrence; in regard to comorbidity and mortality associated with the procedure, endoscopy is superior. Conclusions and implications: There is no evidence from clinical trials. In these meta-analyses, surgical therapies showed superiority in survival, and endoscopic therapies showed superiority in control of mortality related to cancer with a high rate of disease recurrence; also, comorbidity and mortality associated with endoscopy are superior. Prospective, controlled trials with large sample sizes are required to confirm the results of this current meta-analysis. Systematic review registration number: CRD42014013170