Orientadores: Sophie Françoise Mauricette Derchain, Luiz Carlos Zeferino / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-05T02:58:59Z (GMT). No. of bitstreams: 1 Oliveira_ElianeReginaZambelliMesquitade_D.pdf: 6493304 bytes, checksum: a5f29a6631b19fe71c5a0f57f35863e5 (MD5) Previous issue date: 2005 / Resumo: Objetivos:Avaliar a detecção de Papilomavírus humano (HPV) de alto risco oncogênico pelo teste de Captura Híbrida 11(CH 11)em mulheres com resultado da colpocitologia oncológica sugestiva de atipias de células glandulares (ACG). Sujeitos e métodos: Estes três trabalhos foram realizados através de um estudo de corte transversal com mulheres encaminhadas com ACG ou Adenocarcinoma in situ (AIS) no exame de rastreamento de câncer cervical. Para o terceiro objetivo, estas mulheres foram comparadas com um grupo de pacientes atendidas por lesões escamosas de alto grau (HSIL). O estudo foi realizado no Ambulatório de Patologia Cervical e no Laboratório de Citologia do Centro de Atenção Integral à Saúde da Mulher (CAISM) da Universidade Estadual de Campinas (UNICAMP) no período de Novembro de 2001 a Março de 2004. As mulheres foram submetidas à coleta de amostra cervical para citologia convencional e teste de CH 11para detecção do DNA-HPV de alto risco oncogênico, e avaliação colposcópica. Todas mulheres com anormalidades citológicas persistentes ou alterações colposcópicas foram submetidas à biópsia cervical colpodirigida, conização com alça ou a frio. Resultados: No primeiro artigo, foram incluídas 91 mulheres encaminhadas por citologia com ACG, sendo que o resultado da segunda citologia foi normal em 28 casos (31%), com ACG em 17 casos (19%) e 24 casos com HSIL ou lesões mais graves (26%). O teste de CH 2 foi positivo em 36% dos casos, sendo o DNA-HPV detectado em 87% das mulheres com HSIL, em 100% das mulheres com AIS, 24% das mulheres com ACG e em apenas 11% das mulheressem anormalidades citológicas. No segundo artigo, foram avaliadas 146 mulheres encaminhadas por citologia com ACG, ACG associadas a HSIL e AIS, e a prevalência total de DNAHPV de alto risco oncogênico foi de 38%. O DNA-HPVfoi detectado em 93% das mulheres com ACG associado a HSIL e em 71% daquelas citologias com AIS. Já, as mulheres com ACG puras tiveram uma prevalência de 29% na detecção do DNA-HPV. Quarenta e cinco mulheres (30,8%) tinham NIC 2 ou lesões mais graves. O DNA-HPVde alto risco foi detectado em apenas 16% das mulheres que não apresentaram lesões histológicas, em contraste com 96% das mulheres com NIC 2 ou NIC 3 e 75% das mulheres com AIS. As mulheres com carcinoma cervical invasivo, escamoso ou glandular, apresentaram DNA-HPV de alto risco detectável em 85% dos casos. A detecção do DNA-HPV esteve significativamente associada com o diagnóstico histológico de NIC 2 ou lesões mais graves. No terceiro artigo, foram avaliadas 247 mulheres que apresentavam na análise histológica 38 (15%) cervicites, 194 (75%) lesões escamosas e 15 (9%) de neoplasia glandular.Apenas 30% das pacientes com ACG e HPV negativo tiveram alguma lesão glandular ou escamosa em comparação com 76% das mulheres com ACG e HPV positivo. Nas mulheres com ACG e HSIL, a maioria das lesões histológicas, NIC 2 ou mais graves, foi associada ao teste de HPV positivo. A maioria das lesões (95%) encontradas nas pacientes com ACG e HSIL foi de natureza escamosa, e a CH II não contribuiu para a diferenciação de lesões glandulares. Conclusões: A segunda citologia associada ao teste para detecção do DNA-HPV de alto risco oncogênico pode melhorara conduta nas mulheres com ACG detectado na citologia de rastreamento. A detecção do DNA-HPV esteve fortemente associada com a gravidade da lesão histológica cervical nas mulheres com citologia com ACG ou AIS. O teste de HPV pôde auxiliar na identificação de lesões significativas escamosas ou glandulares, porém não foi capaz de discriminar as lesões glandulares das escamosas / Abstract: Objectives: Detection of high-risk human papillomavirus(HPV) DNA by hybrid capture 2 (HC 2) in women referred due to atypical glandular cells (AGC) in the primary screening. Subjects and Methods: A cross-sectional study was conduded on women referred due to AGC or adenocarcinoma in situ (AIS) in the primary screening. These women were compared with a group that had high-grade squamous intraepitheliallesion (HSIL). The study was conduded at the Cervical Patology Ambulatory and Cytology Laboratory of the Centro de Atenção Integral à Saúde da Mulher at the Universidade Estadual de Campinas from November 2001 to March 2004. Cervical sample had been colleded for conventional cytology and HPV testing by HC II. The colposcopy had been performed and all women with persistent cytology abnonnalities or colposcopy abnormalities were submitted a cervical biopsy or conization.Results: In 91 women induded in the first paper, a second Pap smear was taken and HPV-DNA test was performed using HC II. The second Pap smear showed no abnormalities in 28 (31%) cases, ACG in 17 (19%) cases and HSIL or worse in 24 (26%). HC II test was positive in 36% of the altogether cases. Considering the second Pap smear diagnosis, HPV-DNA was deteded in 87% of the women with HSIL, 100% of women with AIS, 24% of women with AGC and only in 11% of the women with no abnormalities. In the second paper, the overall prevalence of HPV-DNA was 38%. HPV-DNA was detected in 93% ofthe women with HSIL associated with AGC and in 71% of women with AIS at Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had dinically significant histologicallesions (CIN 2 or worse). High-risk HPV-DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% ofthose who had CIN 2 or CIN 3 and 75% of women with AIS. Women with invasive carcinoma (squamous cells or adenocarcinoma) had over 75% of HPVDNA positivity. The last paper histological analysis disdosed 38 (15%) cervicitis, 194 (75%) squamous lesions and 15 (9%) glandular neoplasia. Only 30% of AGC-HPV negative patients have a pathologically proven cervical lesion, whereas 76% of women with AGC-HPV positive have been diagnosed with some squamous or glandular lesion. In women with AGC-HSIL, the proportion with significant histological lesion was higher when HPV test was positive. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV do not contribute its differentiation trom glandular. Conclusion: The use of the second Pap smear combined with HPV-DNA may improve the management of women with AGC detected in the primary screening. HPV-DNA detection was significantly associated with the severity of cervicallesion (CIN 2 or worst) in women referred for AGC or AIS in their Pap smear. HPV test should help to identify significant squamous or glandular lesion among women referred due to glandular or squamous abnormalitiesat Pap smear, however the test are unable to discriminate glandular from squamous lesion / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

Orientadores: Luiz Carlos Zeferino, Sophie Françoise Mauricette Derchain / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-05T06:31:51Z (GMT). No. of bitstreams: 1 Santos_SilviaHelenaRabelodos_D.pdf: 2847930 bytes, checksum: ef79106a00058e70bc6551562ff48111 (MD5) Previous issue date: 2005 / Resumo: Objetivo: Analisar a associação do tipo de HPV e das variantes dos HPV 16 e 18 com lesão neoplásica do colo uterino em mulheres cujo exame citológico apresenta anormalidades em células glandulares endocervicais. Métodos: Este estudo de corte transversal analítico incluiu 160 mulheres com citologia cervical de rastreamento, sendo 93 mulheres com células glandulares atípicas sem outras especificações (AGC-SOE), 18 com células glandulares atípicas provavelmente neoplásicas (AGC-NEO), 35 com por AGC associado a lesões intra-epitelias escamosas de alto grau (HSIL) e 14 com adenocarcinoma in situ (AIS). No primeiro atendimento foi colhido material cervicovaginal para pesquisa de DNA de HPV, segundo esfregaço cervical, e foi realizada colposcopia em todas as mulheres. Biópsias e/ou conizações foram realizadas em 129 pacientes. Trinta e uma mulheres encaminhadas por diagnóstico citológico de AGC-SOE com colposcopia normal e segunda citologia com resultado negativo foram seguidas a cada quatro meses com exames citológicos e colposcópicos. Todas as mulheres incluídas foram submetidas a ecografia pélvica. A pesquisa de DNA-HPV foi feita por PCR, utilizando os primers PGMY09 e PGMY11, e a genotipagem foi realizada através de hibridização reversa em pontos. A determinação das variantes de HPV 16 e HPV 18 foi realizada através de sequenciamento. Resultados: Dos 129 casos com avaliação histológica, 75 (58%%) mostraram diagnósticos neoplásicos (intra-epiteliais e invasivos). A maioria dos diagnósticos neoplásicos foi categorizada como de origem escamosa (77%). A prevalência total de HPV foi de 43%. O HPV 16 foi o mais prevalente e esteve significantemente associado a neoplasias escamosas (NIC 2 ou lesão mais grave) e neoplasias glandulares (AIS ou lesão mais grave). O HPV 18 foi o segundo tipo mais prevalente e esteve significativamente associado a neoplasias glandulares. Maior diversidade na distribuição dos tipos foi observada nos diagnósticos histológicos de NIC 2 e NIC 3. As neoplasias glandulares foram exclusivamente relacionadas aos tipos 16 e 18. O estudo de variantes incluiu 24 casos HPV 16 positivos e 6 casos HPV 18 positivos. Variantes Européias e Não Européias (Ásia-Americanas) foram detectadas, respectivamente, em 62% e 38% dos casos HPV 16 positivos. Variantes Européias de HPV 18 também foram mais prevalentes (3/6). Neoplasias glandulares foram mais prevalentes e significativamente associadas a Variantes Ásia-Americas de HPV 16. Variantes Européias de HPV 16 foram mais prevalentes em neoplasias escamosas. Neoplasias glandulares também foram associadas aos HPV 18, mas a análise de suas variantes não foi conclusiva, devido ao pequeno número de casos. Conclusão: Os HPV estão associados ao tipo histológico de neoplasia cervical detectada em mulheres com anormalidades em células glandulares endocervicais, contudo a identificação dos tipos não é suficiente para explicar o padrão histológico, uma vez que o HPV 16 pode estar associado com neoplasias escamosas e glandulares. A associação do HPV 16 com neoplasias escamosas e glandulares é explicada por suas variantes. Variantes Ásia-Americanas associam-se às neoplasias glandulares, enquanto variantes européias associam-se às neoplasias escamosas / Abstract: Objective: To analyze the association between the different genotypes of oncogenic human papillomavirus (HPV) and HPV 16 and HPV 18 variants with histological diagnosis in women referred for glandular endocervical abnormalities in their cervical smear. Methods: This cross sectional study included a series of 160 women. Atypical Glandular Cells (AGC) not otherwise specification (NOS), AGC favor neoplastic (FN) were the only diagnosis in 93 and 18 women respectively. Thirty five patients had both AGC and high grade squamous intraepithelial lesion (HSIL). Fourteen women were diagnosed as adenocarcinoma in situ (AIS). All women were subjected a collection of sample for HPV-DNA testing and second cervical smear and underwent a colposcopic examination. Biopsies or conizations were done in 129 due to colposcopically abnormal area or second abnormal cervical smear result. In 31 women, referred due to AGC-NOS at screening cervical smear with adequate and normal colposcopy and second cervical smear results, follow up each 4 months with new cytology and colposcopy were done and the final diagnosis was considered as non-neoplastic. All women had pelvic ultrasound examination. The HPV-DNA testing was done by PCR using the set of PGMY09 e PGMY11 with genotyping by linear array hybridization. The molecular variants of HPV 16 and 18 were tested using PCR sequencing. Results: Among 129 women with histologic evaluation, 75 (58%) revealed neoplastic diagnoses (intraepithelial and invasive); of them the majority (77%) were of squamous cell origin. The overall prevalence of HPV was 43%. HPV 16 was the most prevalent genotype and was significantly associated with squamous neoplasias (CIN 2 or worse) and glandular neoplasias (AIS or worse). HPV 18 was the second most prevalent and was significantly associated with glandular neoplasias. Major diversity on HPV distribution was observed in Cervical Intraepithelial Neoplasia (CIN) 2 and CIN 3 histologic diagnosis. The variants study included 24 cases HPV 16 positives and 6 cases HPV 18 positives. European Variants and Asian-American Variants were detected in 62% and 38% of HPV positives cases. European variants of HPV 18 also were more prevalent (3/6). Asian-American HPV 16 variants were significantly associated with glandular neoplasia and European variants were more prevalent in squamous neoplasias. Glandular neoplasias also were associated with HPV18 but in this study the analysis of its variants was not conclusive. Conclusion: The HPV genotypes are associated with histological type of the cervical neoplasia, but HPV genotypes is not enough to explain at whole, since the HPV 16 were associated with squamous and glandular neoplasia. The association of HPV 16 with squamous or glandular neoplasia is explained by its variants. Squamous neoplasias were nearly related to HPV 16 European variants and glandular neoplasias were related to HPV 16 Asian-American / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

L’adénocarcinome pancréatique canalaire est un cancer de mauvais pronostic avec une survie à 5 ans inférieure à 5% et une médiane de survie d’environ 6 mois. Dès les stades précoces de la carcinogenèse pancréatique, la mucine membranaire MUC1, glycoprotéine de haute masse moléculaire, est surexprimée et présente des anomalies de distribution cellulaire, essentiellement une délocalisation membranaire vers le pôle basolatéral et une rétention à l’intérieur de la cellule. Sachant que MUC1 est capable d’interagir avec l’EGFR et de jouer un rôle sur la transduction des signaux, cette séquestration pourrait être à l’origine de signaux oncogéniques et est utilisée par les pathologistes comme indicateur de malignité après ponction sur des lésions pancréatiques. Cependant, les mécanismes permettant cette rétention cytoplasmique ne sont pas connus. Des études antérieures du laboratoire ont montré que le trafic de certaines glycoprotéines vers la membrane apicale des cellules épithéliales était dépendant de la Galectine 4. Dans ce travail, nous nous intéresserons à la Galectine 3, lectine endogène susceptible d’interagir avec les motifs glycanniques des mucines et aussi des récepteurs membranaires. Cette Galectine est surexprimée dans le cancer pancréatique et son expression est corrélée à une forte agressivité tumorale dans d’autres cancers. Le but de ce travail a été dans un premier temps de mettre au point des lignées cellulaires pancréatiques polarisées CAPAN-1 Knocked-down pour la Galectine-3. Dans un second temps d’étudier l’implication de la Galectine-3 : (i) dans le trafic intracellulaire de MUC1 et l’EGFR (ii) dans l’interaction entre MUC1 et l’EGFR (iii) sur les voies de signalisation de l’EGFR.Les résultats montrent que les cellules tumorales pancréatiques CAPAN-1 présentent les anomalies de distribution cellulaire de MUC1 observées dans les tumeurs pancréatiques humaines, notamment la rétention de MUC1 à l’intérieur des cellules. Le silencing de la Galectine-3 entraîne la disparition de cette anomalie de distribution cellulaire, MUC1 retrouvant la distribution membranaire normale. Nous avons montré que l’inhibition de l’expression de la Galectine-3 est associée (i) à une augmentation de la translocation nucléaire de l’EGFR (ii) à une inhibition de l’endoyctose de MUC1 et de l’EGFR en condition de sevrage. Ce phénomène s’accompagne d’une augmentation de l’interaction entre MUC1 et l’EGFR et d’une activation accrue de ce récepteur tyrosine kinase lorsqu’il est soumis à l’EGF : augmentation de la phosphorylation de l’EGFR et augmentation de la phosphorylation des MAPK Erk1 et 2. Mots clés : Galectine, Mucine, EGFR, cancer, endocytose, translocation nucléaire / Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from the epithelial ductal cells. In physiological state, the transmembrane mucin MUC1 is expressed at the apical pole where it protects the cell, senses the environment and modulates signal transduction notably by interacting with EGFR. In tumor cells, the localization of MUC1 is modified. MUC1 expression at the membrane becomes circumferential and accumulates in the cytoplasm. This sequestration is thought to deliver oncogenic signals to the cell, and is used by pathologists as an indicator of malignancy. Since it was previously demonstrated that endogenous lectins, especially galectin-3 (Gal-3) and -4, control the apical targeting of glycoproteins in epithelial cells, our aim was to study the role of Gal-3 in the control of MUC1 expression topography in PDAC, and in the cell invasiveness in vitro. Results/expected results: In control cells, we observed a strong MUC1 labeling in cytoplasm as in pathologic conditions. MUC1 was partially co-localized with M6PR in late endosomes. In KD cells, invalidation of Gal-3 led to a strong decrease of MUC1 cytoplasmic labeling. Gal-3 down-regulation is associated with a decrease of both MUC1 and EGFR protein levels by WB. However, KD Gal-3 cells expressed 2-fold higher levels of phosphoY1173EGFR in response to EGF treatment. Preliminary results showed that KD Gal-3 cells lost their in vitro invasive phenotype.Conclusions: Our data showed that Gal-3 is responsible for MUC1 cytoplasmic retention in pancreatic tumor cells. Silencing of Gal-3 promotes MUC1 localization at the cell membrane, and increases EGF-induced EGFR phosphorylation.keywords : Galectine, Mucine, EGFR, cancer, endocytose, translocation nucléaire

Abstract Manganese superoxide dismutase (MnSOD) is an important intracellular antioxidant enzyme, which has been suggested to play a role in tumour biology. In the present study, the expression and possible role of MnSOD in malignant pleural mesothelioma was investigated. Mesothelial cells in healthy visceral pleural tissue showed no MnSOD immunoreactivity in five out of six cases, whereas moderate or high immunoreactivity for MnSOD was detected in 30 out of 42 (71%) cases of mesothelioma. Only two of the 21 cases with metastatic adenocarcinoma of the pleura showed moderate MnSOD immunoreactivity, the remaining 19 (90.5%) showing negative or weak reactivity (p < 0.001, by Fisher's exact test compared to mesothelioma). The immunostaining of catalase, a hydrogen peroxide scavenging antioxidant enzyme, was detectable in 27 of the 35 (77%) mesothelioma cases studied, whereas all the five samples of healthy pleural mesothelium were negative. Reactive mesothelium showed positive immunoreactivity for MnSOD and catalase, suggesting that induction of these enzymes is not specific for mesothelioma. Two continuous human mesothelioma cell lines showed higher MnSOD activity, immunoreactive protein and mRNA levels than non-malignant mesothelial cells. In addition, mesothelioma cells expressing the highest MnSOD levels had the highest levels of catalase and copper-zinc superoxide dismutase. The mitochondria of these cells expressed higher MnSOD and lower superoxide levels than non-malignant mesothelial cells. The mesothelioma cells with the highest antioxidant enzyme levels were most resistant to oxidant- and drug-induced injury and to drug-induced apoptosis compared to non-malignant mesothelial cells and mesothelioma cells with lower MnSOD and catalase levels. The extent of cell proliferation and apoptosis of mesothelioma tissue were 14.1±13.2% and 1.1±1.2%, respectively. MnSOD expression was inversely associated with cell proliferation (p = 0.02 by t-test), and a tendency for a better prognosis among patients with moderate or strong MnSOD expression was demonstrated. Patients displaying a tumour with enhanced proliferation or apoptosis had a poorer prognosis (p < 0.001 by Log Rank test). In conclusion, the MnSOD level is usually high in pleural mesothelioma, which may affect the proliferation and drug-resistance of mesothelioma cells. MnSOD immunostaining can thus possibly be used to distinguish mesothelioma from metastatic adenocarcinoma but not from reactive mesothelium.

Orientador: Liliana Aparecida Lucci De Angelo Andrade / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-20T16:42:37Z (GMT). No. of bitstreams: 1 Marques_Terezinha_M.pdf: 5257490 bytes, checksum: a7ce79d4f8daa915ba77c12058973de4 (MD5) Previous issue date: 1995 / Resumo: Metaplasia tubária (MT) é uma lesão de natureza benigna que pode oferecer dificuldade para o diagnóstico diferencial com adenocarcinoma in situ (AIS) na endocérvice. Sua correta caracterização e identificação evita condutas terapêuticas inadequadas. Selecionamos IS casos de MT e 16 casos de AIS, morfologicamente característicos com o método hematoxilina-eosina. A seguir, examinamos por meio de reações histoquímicas e imuno-Mstoquímicas, para avaliar seu comportamento e tentar contribuir para o diagnóstico diferencial- Utilizamos colorações para mucinas, Alcian blue (AB), mucicarmim (MC), PAS e PAS com diastase (PASd), além de anticorpos anti-antígeno cárcino-embrionário (CEA) e anri-vimentína (VIM). Os métodos histoquírnicos não demonstraram diferença significativa entre as duas lesões. Apesar do CEA ser mais freqüente nos casos de adenocarcinoma in situ, o papel da vimentina foi decisivo no diagnóstico diferencial, porque resultou positiva em 78% dos casos de metaplasia tubária e negativa em todos os casos de adenocarcinoma in situ / Abstract: Endocervical tubal metaplasia, a benign lesion, is known to be frequently misdiagnosed as adenocarcinoma in situ. Its correct identification is needed in order to avoid inadequate managements. We selected 18 cases of endocervical tubal metaplasia and 16 of adenocarcinoma in situ. Only specimens that had morphologic appearences typical for either tubal metaplasia or adenocarcinoma in situ were chosen. All cases were analysed by hematoxilin-eosin, stains for mucin, Alcian blue pH 2.5, mucicarmine, PAS and PAS diastase, and submitted to immunoperoxidase reaction for carcinoembryonic antigen and vimentin. Statistical analysis demonstrated no signifficant difference in the reactions for mucins between the lesions. Whereas CEA was more frequently positive in AIS than in TM cases, VIM was negative in all cases of AIS and positive in 78% of TM cases and was therefore considered more useful for the differential diagnosis / Mestrado / Mestre em Ciências Médicas

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21991号 / 医博第4505号 / 新制||医||1037(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 武田 俊一, 教授 坂井 義治, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24523号 / 医博第4965号 / 新制||医||1065(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 川口 義弥, 教授 藤田 恭之, 教授 波多野 悦朗 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

OBJECTIVE: The incidence of endocervical adenocarcinoma has increased steadily over the past two decades. Since the Bethesda System was introduced, the diagnosis of atypical glandular cells of undetermined significance (AGUS) has also risen and now accounts for 0.461.83% of all cervical (Pap) smears. The purpose of this study was to evaluate the significance of a diagnosis of A GUS using cytohistologic correlation. STUDY DESIGN: A retrospective review of archival material from 1993 through 1996 identified 64 patients who had smears diagnosed as AGUS and had a subsequent surgical biopsy. The smears were reviewed and cytologic features analyzed and correlated with the histologic diagnosis. RESULTS: On biopsy, 3 (5%) of the 64 cases showed endocervical adenocarcinoma in situ (AIS) (1 case with invasive adenocarcinoma also), 14 (22%) had a benign glandular lesion (endocervical polyp, tubal metaplasia, microglandular hyperplasia, reactive changes), 35 (54%) had squamous intraepithelial lesion (SIL) (15 diagnosed on the original smear), and 12 (19%) had no abnormality. Among the cytologic criteria evaluated, feathering (P = .01), palisading (P < .001) and chromatin clearing (P = .002) were shown to have a significant association with the histopathologic diagnosis of AIS/adenocarcinoma. These features were also useful in distinguishing AIS/adenocarcinoma from SIL and benign glandular changes from AIS/adenocarcinoma but not benign/reactive glandular changes from SIL. CONCLUSION: A diagnosis of AGUS correlated with a clinically significant lesion in the majority of cases. Squamous dysplasia (SIL) was the most common lesion identified. The presence of feathering, nuclear palisading and chromatin clearing increased the likelihood of a histologic diagnosis of AIS/adenocarcinoma.

Colorectal cancer is one of the leading causes of cancer related deaths in western world. While most common site for metastasis for colon cancer is liver, lung, and the peritoneum, metastasis to various other organs such as brain, bones and thyroid has been reported. Metastatic lesions to the small bowel are more common than primary lesions and most common primary neoplasms that metastasize to the duodenum are lung cancer, renal cell carcinoma, breast cancer, and malignant melanoma. We report a very rare case of recurrent adenocarcinoma of colon metastasizing to duodenum after 2 years of curative resection of primary cancer. Surgical resection for curative intent as well as palliative management is recommended.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24186号 / 医博第4880号 / 新制||医||1060(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 中山 健夫, 教授 平井 豊博, 教授 中本 裕士 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM