Made available in DSpace on 2014-06-11T19:25:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-27Bitstream added on 2014-06-13T20:53:04Z : No. of bitstreams: 1 hasimoto_cn_me_botfm.pdf: 997736 bytes, checksum: 169b74e48900c8a0542d8476b77ece89 (MD5) / Universidade Estadual Paulista (UNESP) / A perfuração esofágica é uma entidade clínica rara, difícil e desafiadora. Seu manejo adequado, ainda nos dias de hoje, permanece controverso e, apesar dos avanços nas técnicas cirúrgicas, reanimação, cuidados intensivos e antibioticoterapia, a mortalidade permanece elevada. Avaliar qual tratamento é mais eficaz para a perfuração esofágica: o tratamento reparador ou o tratamento conservador. Revisão sistemática de ensaios clínicos randomizados, quaserrandomizados e estudos controlados. As seguintes bases de dados foram pesquisadas: Pubmed, CENTRAL (the Cochrane Library), Embase e Lilacs. A data da última busca foi em abril de 2011. Foi planejado considerar ensaios clínicos que avaliassem o tratamento reparador versus conservador em pacientes com perfuração esofágica. Dois revisores, independentemente, selecionaram os estudos em potencial. 3.311 referências foram identificadas pelas principais bases de dados eletrônicas. Deste total, 62 artigos foram selecionados para potencial inclusão na revisão. Entretanto, estes estudos foram classificados, em sua maioria, como série de casos retrospectivos e, desta forma, nenhum estudo preencheu os critérios de inclusão da revisão. Não há evidências de nível Ib, de acordo com a classificação do Centro para Medicina Baseada em Evidências de Oxford (CEBM), para definir a eficácia dos tratamentos reparador e conservador na perfuração esofágica. Há urgência da realização de ensaios clínicos para responder a esta questão clínica de relevância baseando-se no protocolo de revisão sistemática apresentado neste capítulo e, no momento, a tomada de decisões deve ser norteada em níveis de evidências inferiores, neste caso, série de casos retrospectivos / Esophageal perforation is a rare, difficult and challenging clinical issue. Management strategies even these days remain controversial and in despite of technological advances in surgical techniques, resuscitation, intensive care and antibiotic therapy, mortality remains high. To assess which treatment is most effective for esophageal perforation cases, repair or conservative treatment. Systematic review of randomized controlled trials, quasi-random method and controlled studies. She following databases were searched: PubMed, CENTRAL (the Cochrane Library), Embase and Lilacs. The date of the last search was in April, 2011. It has been planned to consider clinical trials to analyze the repair versus conservative treatment in patients with esophageal perforation. Two reviewers selected potential studies independently. 3,311 references were identified by the major electronic databases. From the total, 62 articles were selected as potential for the inclusion in the review. However, these studies were classified mostly as a retrospective cases series and, thus, no studies met the criteria to be included in the review. No evidences of level Ib according to the the Center for Evidence Based Medicine in Oxford (EMBC) classification to define the efficacy of the repair and conservative treatments in esophageal perforation. It is urgent to carry out clinical trials to respond to this clinical relevant issue, based on the systematic review protocol presented in this chapter and, at the moment, decisions should be guided in lower levels of evidence, in this case, retrospective case series

Le cancer de l’œsophage est un cancer particulièrement agressif, avec 450 000 nouveaux cas par an dans le monde. Malgré les récentes innovations thérapeutiques en oncologie, la radiochimiothérapie reste le traitement standard dans ce cancer. Ce traitement lourd est pourtant peu efficace, puisque la survie des patients 5 ans après le diagnostic atteint seulement 20%. Une meilleure connaissance des mécanismes moléculaires ainsi que de nouveaux marqueurs pronostics sont nécessaires afin de réaliser une avancée significative dans la compréhension du cancer de l’œsophage. L’objectif de ce travail concerne l’investigation de nouveaux paramètres pronostiques, macro- ou microenvironnementaux.Dans ce cadre, nous avons investigué l’impact de la composition corporelle et, plus particulièrement, de la qualité du tissu adipeux des patients sur leur survie générale. Les patients souffrant d’un cancer de l’œsophage présentent en général un statut nutritionnel complexe :l’obésité est un facteur de risque de développement d’un adénocarcinome de l’œsophage, tandis que les carcinomes épidermoïdes se développent fréquemment chez des patients malnutris. Nous avons montré que l’atténuation du tissu graisseux au CT-scan a un impact pronostique important. Spécifiquement, une faible densité de la graisse sous-cutanée et viscérale sont des facteurs pronostiques bénéfiques majeurs. Des résultats similaires ont été publiés pour d’autres cancers digestifs, notamment par notre équipe pour le cancer colorectal métastatique. Cependant, les mécanismes biologiques sous-tendant les variations de densité de ces tissus graisseux restent encore incertains. Un tissu graisseux de haute densité refléterait des adipocytes beiges, pauvres en triglycérides et métaboliquement plus actifs. Alors que des phénomènes extrinsèques à la tumeur pourraient amorcer ce phénomène, les facteurs sécrétés par la tumeur pourraient empirer ce processus et impacter l’état de santé général du patient. Nos résultats suggèrent que les traitements pourraient également aggraver ce mécanisme. L’analyse d’échantillons sanguins et de biopsies graisseuses de patients souffrant de cancers gastro-intestinaux nous permettra de dévoiler des marqueurs associés à la variation de densité graisseuse et de faire la lumière sur les mécanismes biologiques impliqués.Depuis quelques années, les motifs histopathologiques de croissance tumorale ont été l’objet de plusieurs études. Associés aux mutations génétiques de la tumeur mais aussi à son microenvironnement, ces motifs de croissance constituent le reflet de processus oncogéniques complexes. Nous avons d’abord exploré l’impact pronostique des motifs histopathologiques de croissance tumorale œsophagienne sur deux cohortes de patients. Nous avons confirmé l’impact pronostique négatif des tumeurs infiltrantes par rapport aux tumeurs expansives. Les tumeurs infiltrantes étaient également plus fréquemment associées à un Stade T et N plus avancés, ainsi qu’à la présence d’emboles lymphovasculaires et d’infiltrations péri-nerveuses. Nous avons ensuite exploré les voies de signalisation classiquement dérégulées dans la carcinogenèse sur la cohorte composée de données publiques ;ces analyses nous ont permis d’identifier l’angiogenèse, la transition épithélio-mésenchymateuse et l’inflammation comme étant surexprimées dans les tumeurs infiltrantes. Nous avons pu identifier OLR1, SFRP4 et CXCL9 comme étant trois gènes intéressants à investiguer pour chacune de ces voies, respectivement.Ces résultats n’ont pas été confirmés par qPCR dans la cohorte de validation. La qualité de l’ARN et le traitement pré- opératoire de ces patients ont réduit le nombre de patients analysables et vraisemblablement contribué à un biais important d’expression des mécanismes biologiques. Une analyse plus extensive de ces trois voies de signalisation pourrait distinguer des acteurs importants du développement de ces motifs de croissance tumorale.En conclusion, ce travail exploratoire a permis de définir plusieurs acteurs du pronostic des patients atteints d’un cancer de l’œsophage. Des analyses moléculaires supplémentaires permettront d’aborder les voies biologiques sous- tendant le développement des motifs histopathologiques de croissance tumorale, d’une part et de variation de densité du tissu graisseux, d’autre part. Ce travail permettra de dévoiler des aspects complexes et encore peu étudiés de l’agressivité des tumeurs œsophagiennes. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23375号 / 医博第4744号 / 新制||医||1051(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中本 裕士, 教授 松田 秀一, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduction: The incidence of adenocarcinoma of the esophagus has increased dramatically in the past three decades. Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer death. Squamous cell cancer is the most common type of esophageal cancer all over the world, but the incidence of esophageal adenocarcinoma has been increasing. Most, if not all, esophageal adenocarcinomas arise from a region of Barrett's metaplasia. The most common location is near the EG junction with an association of endoscopic evidence of Barrett's esophagus. We present a case of young male presented with lower extremity pain and swelling due to metastasis of undiagnosed primary esophageal cancer. Case Presentation: A 36-year-old male with no significant medical history presented with complaints of lower extremity pain and swelling. Patient denied any other symptoms. On admission, vital signs were temp. 97.8, BP 145/87 mmhg, HR 75 bpm, RR was 18. Labs work showed Na 141, K 3.7, BUN 17, Cr 0.70, Alkaline phosphatase 263, AST 14, ALT 9, CHOL 202, HDL 27, Triglyc 285, Hgb 12.4, Plt 244, Wbc 9.6, ESR 28, TSH 7.07, Vit D (25 hydroxy) 8, Hgb A1c 7.0, CRP 102.6. Knee x-ray was highly suspicious for chronic osteomyelitis vs. neoplastic lesion. Doppler US of lower extremity ruled out DVT, but showed large complex fluid collection anterior to the knee and proximal leg measuring 8.0 x 5.8 x 18.6 cm with concern for osteomyelitis with overlying abscess vs an aggressive primary bone tumor. Patient was started on antibiotics and had a MRI that showed periostitis with possible differential of osteomyelitis/periostitis and osteosarcoma. CT scan of chest, abdomen and pelvis showed aortocaval and left iliac lymphadenopathy concerning for metastasis. Blood cultures were negative but biopsy was consistent with metastatic adenocarcinoma favoring gastrointestinal and pancreaticobiliary tract as the primary source. Patient had an upper endoscopy that showed esophageal mass extended from the GE junction up about 7cm. Chemotherapy and radiation therapy were initiated. HER-2 gene was ordered. Patient developed cardiopulmonary arrest and died prior to discharge. Discussion: Adenocarcinoma of the esophagus is usually associated with Barrett's esophagus that involves the lower third of esophagus. It is a very aggressive disease associated with diffuse metastasis and high mortality rate. The most common metastatic sites for esophageal cancer are liver brain and lung. Risk factors associated with cancer are smoking, higher body mass index, gastroesophageal reflux disease, and a diet low in fruits and vegetables. Almost half of the cases of adenocarcinoma have no associated reflux disease. The median survival rate of metastatic esophageal cancer is 4-9 months. Physicians should always think of visceral malignancy in cases of biopsy proven adenocarcinoma for better prognosis. Endoscopy should always be done to look for visceral malignancy if cancer is suspected.

No description available.

No description available.

Objetivo: Avaliar o perfil funcional do esôfago e a prevalência de refluxo gastroesofágico (RGE) em pacientes candidatos a transplante pulmonar. Métodos: Foram analisados prospectivamente entre Junho de 2005 a Novembro de 2006, 55 pacientes candidatos a transplante pulmonar da Santa Casa de Misericórdia de Porto Alegre. Os pacientes foram submetidos a esofagomanometria estacionária e pHmetria esofágica ambulatorial de 24 horas de um e dois eletrodos antes de serem submetidos ao transplante pulmonar. Resultados: A esofagomanometria foi anormal em 80% dos pacientes e a pHmetria revelou RGE ácido patológico em 24%. Os sintomas digestivos apresentaram sensibilidade de 50% e especificidade de 61% para RGE. Noventa e quatro por cento dos pacientes com DPOC apresentaram alteração à manometria, sendo a hipotonia do esfíncter inferior o achado mais frequente (80%). Pacientes com bronquiectasias apresentaram a maior prevalência de RGE (50%). Conclusões: RGE é achado freqüente em pacientes com doença pulmonar avançada. Na população examinada, a presença de sintomas digestivos de RGE não foi preditiva de refluxo ácido patológico. A contribuição do RGE na rejeição crônica deve ser considerada e requer estudos posteriores para seu esclarecimento. / Objective: To assess the prevalecence of gastro-esophageal reflux (GER) and esophageal motor profile in lung transplant candidates. Methods: Between July 2005 and November 2006, a prospective study was conducted in 55 candidates for lung transplantation. Patients underwent esophageal manometry and 24-hour pH testing before undergoing transplantation as an attempt to obtain the prevalence of reflux in this subset. Results: Abnormal esophageal manometry was documented in 80% of the patients and abnormal GER was documented in 24% of the patients. Reflux-related symptoms presented sensitivity and specificity of 50% and 61% for GER, respectively. Ninety-four per cent of the patients with COPD presented an abnormal esophageal manometry, and hipotensive lower esphincter was the most common finding (80%). Bronchiectasis patients presented the highest prevalence of GER (50%). Conclusions: GER is highly prevalent in end-stage lung disease. Reflux-related symptoms was not preditive of gastroesophageal reflux. The contribuition of GER to chronic rejection and allograft dysfunction must be considered and needs to be addressed in future studies.

Primary esophageal (E) and gastro-esophageal junction (GEJ) cancer xenografts have the potential to become useful pre-clinical models of disease. In this study, we determined that p16 negative tumors that have not been exposed to neo-adjuvant chemo-radiation have higher engraftment chances. Morphological features and expression of certain molecular markers (p53, p16, Ki-67, EGFR, Her-2/neu) suggest that no major changes occur between primary tumors and xenografts or between early passage and late passage xenografts. Global gene expression data supported these results but revealed that approximately 2000 genes differed significantly between passage one xenografts and human tumors. Most of these genes, however, might coincide with stromal signals present in patient tumors but absent in xenografts. Primary E/GEJ cancer xenografts also showed a wide range of chemosensitivities to cisplatin-paclitaxel treatment, confirming the usefulness of these models in drug testing. These models also revealed potential ways to interrogate tumor initiating cell (TIC) dynamics after chemotherapy.

Primary esophageal (E) and gastro-esophageal junction (GEJ) cancer xenografts have the potential to become useful pre-clinical models of disease. In this study, we determined that p16 negative tumors that have not been exposed to neo-adjuvant chemo-radiation have higher engraftment chances. Morphological features and expression of certain molecular markers (p53, p16, Ki-67, EGFR, Her-2/neu) suggest that no major changes occur between primary tumors and xenografts or between early passage and late passage xenografts. Global gene expression data supported these results but revealed that approximately 2000 genes differed significantly between passage one xenografts and human tumors. Most of these genes, however, might coincide with stromal signals present in patient tumors but absent in xenografts. Primary E/GEJ cancer xenografts also showed a wide range of chemosensitivities to cisplatin-paclitaxel treatment, confirming the usefulness of these models in drug testing. These models also revealed potential ways to interrogate tumor initiating cell (TIC) dynamics after chemotherapy.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.