Orientadores: Sergio Luis Felisbino, Luis Fernando Barbisan / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-08T07:33:34Z (GMT). No. of bitstreams: 1 Pires_PauloWagner_M.pdf: 1285792 bytes, checksum: 779a7152ec83e03f0f0320e646f206bf (MD5) Previous issue date: 2007 / Resumo: O carcinoma hepatocelular (HCC) é a quinta neoplasia humana mais freqüente no mundo e o abuso crônico do álcool é um conhecido fator de risco, embora uma direta correlação entre o consumo de etanol e o desenvolvimento do HCC permaneça incerta. O presente estudo foi delineado para avaliar os efeitos promotores diferenciais da ingestão crônica de etanol sobre a remodelação e persistência de lesões pré-neoplásicas (LPN) positivas para a forma placentária da glutationa S-transferase (GST-P) e para o fator de crescimento e transformação-alfa (TGF-a) no modelo de hepatocarcinogênese do hepatócito resistente. Noventa e quatro ratos Wistar machos com seis semanas de idade foram aleatoreamente distribuídos em cinco grupos experimentais: grupo G1, controle não-tratado com água e ração basal de livre acesso; G2, não tratado, ração equivalente ao consumo do grupo G3, e maltodextrina dissolvida em água (calorias equivalentes às fornecidas pelo etanol); G3, tratado com etanol a 5% (v/v) na água e ração basal de livre acesso; G4, dietilnitrosamina (DEN, 200 mg/kg de peso corpóreo) e 2-acetilaminofluoreno (2AAF) 200 ppm por três semanas, com ração basal equivalente ao consumo do grupo G5 e maltodextrina dissolvida na água; G5, DEN/2-AAF mais etanol 5% (v/v) e ração basal de livre acesso. Todos os animais foram submetidos à hepatectomia parcial de 70% na 3ª semana e eutanasiados na 12ª e 22ª semanas. Amostras de fígado foram coletadas e processadas histologicamente para detecção de lesões pré-neoplásicas e neoplásicas e contagem de hepatócitos em apoptose em cortes corados por hematoxilina/eosina, análise imunocitoquímica para antígeno nuclear de proliferação celular ¿ PCNA, GST-P e TGF-a e para análise bioquímica de zimografia (atividade de gelatinases). Ao final do tratamento com o etanol, observou-se aumento da porcentagem da área hepática ocupada por LPN GST-P positivas do tipo persistente (P < 0,001), do número de LPN TGF-a-positivas (P< 0,001) e do número e multiplicidade de tumores hepáticos (P < 0.001) em G5, quando comparado com G4. Além disso, observou-se um aumento do índice de proliferação pelo PCNA (fase-S), mas sem alteração nos índices de apoptose, em ambas LPN em remodelação ou persistente em G5 em relação ao grupo G4 ao final da 22ª semana (P <0,001), quando comparado com G4. A atividade de gelatinases (metaloproteinases ¿2 e ¿9) no fígado não foi alterada pelo tratamento com etanol. Os resultados sugerem que a ingestão crônica de etanol promove o crescimento seletivo de LPN GST-P positivas do tipo persistente, especialmente, com associada à co-expressão de TGF-a, sem mudanças na atividades das gelatinases / Abstract: Hepatocellular carcinoma (HCC) is the fifth most frequent cancer in the world and chronic ethanol abuse is a known risk factor, although a direct correlation between ethanol consumption and development of HCC remains uncertain. The present study was designed to evaluate the differential promoting effects of a long-term ethanol intake on remodeling/persistence of gluthatione S-transferase placental form (GST-P) and transforming growth factor alpha (TGF-a) positive preneoplastic lesions (PNL) using the resistant hepatocyte model. Six-week old male Wistar rats were randomly alocated into 5 experimental groups: G1 group, non-treated and water and chow food ad libitum; G2 group, non-treated and pair-fed chow food (restricted to match that of G2 group) and a maltodextrin solution in tap water (matched ethanol-derived calories); G3 group, drinking ethanol 5% ethanol (v/v) and solid food ad libitum;; G4 group, diethylnitrosamine (DEN, 200 mg/kg body weight) plus 200 ppm of 2-acetylaminofluorene (2AAF) for 3 weeks and pair-fed chow food (restricted to match that of G5 group) and a MD solution in tap water (matched ethanol-derived calories); G5 group, DEN/2-AAF treatments plus ethanol 5% (v/v) in tap water and chow food ad libitum. All animals were subjected to 70% partial hepatectomy at week 3 and killed at weeks 12 and 22. Liver samples were collected for histology (preneoplastic and neoplastic lesions and apoptosis detection) and immunohistochemistry (proliferating cell nuclear antigen ¿PCNA, GST-P and TGF-a) and gelatin zymography (metalloproteinases ¿2 and ¿9, also known as gelatinases, activities). At the end of ethanol treatment, there was an increase in percent of liver area occupied by persistent GST-P-positive PNL (P < 0.001), number of TGF-a-positive PNL (P< 0.001) and in number per group and multiplicity of liver tumors (P < 0.001) in DEN/2-AAF-ethanol group (G5) when compared to respective control group (G4 ¿ DEN/2-AAF). In addition, an increase in PCNA labeling indexes (S-phase), but not in the apoptosis rates, in both remodeling and persistent PNL was observed in DEN/2-AAF-ethanol group (G5) at 22 week (P <0.001), when compared to DEN/2-AAF group (G4). Liver gelatinases activities were not altered by ethanol treatment. The results suggest that chronic ethanol. Group(G) at 22 week(P<0.001), when compared to DEN/2-AAF group(G4).Liver gelatinases activities were not altered by ethanol treatment. The results suggest that Chronic ethanol intake promotes a selective growth of persistent GST-P positive PNL, specially, with co-expression of TGF- a, without changes in gelatinases activities / Mestrado / Biologia Celular / Mestre em Biologia Celular e Estrutural

A biomarker of skin cancer would be beneficial in evaluating the efficacy of potential cancer chemoprevention agents. To this end, we investigated the tumor suppresser gene p53 in precancerous actinic keratosis lesions (AK) and malignant squamous cell carcinomas (SCCs) using polymerase chain reaction and single-strand conformation polymorphism analysis (PCR-SSCP) techniques. In addition, p53 protein expression was evaluated using immunohistochemistical analysis with the PAB 1801 monoclonal antibody. Nine out of 13 (69%) SCCs and 8 of 15 (53%) AKs were positive for p53 mutations. In contrast, normal skin samples were negative for p53 mutations. Sequence analysis of AKs and SCCs showed primarily C to T transition mutations. Nuclear immunochemical staining for p53 was observed in 12 15 (80%) AK and 12 13 (92%) SSCs. These results suggest that p53 mutations may be involved in the malignant conversion of AKs to SCCs and that p53 may be useful as a biomarker to study the potential modulatory effects of cancer chemopreventive agents against skin cancer.

Thesis (PhD (Pathology. Anatomical Pathology))--University of Stellenbosch, 2006. / Patients with chronic gastro-oesophageal reflux disease are predisposed to Barrett’s metaplasia and oesophageal adenocarcinoma. The availability of molecular markers that can objectively identify patients with Barrett’s oesophagus at increased risk of carcinoma is highly desirable. A literature search was conducted to identify potentially useful biomarkers for genotype-phenotype correlation studies in South African patients with Barrett’s oesophagus. The COX-2, c-myb and c-myc genes selected for mRNA expression analysis were analysed in 26 patients with Barrett’s metaplasia (BM) without dysplasia; 14 with Barrett’s oesophagus and dysplasia (BD); 2 patients with Barrett’s adenocarcinoma (BAC); 19 with erosive oesophagitis (ERD); 25 with non-erosive oesophagitis (NERD) and 19 control individuals with a normal gastroscopy and no gastro-oesophageal reflux disease (GORD) symptoms. In the BD/BAC group, 69% (11/16) showed increased c-myb mRNA expression compared with 35% (9/26) in the BM group (p = 0.03). A statistically significant difference (p = 0.002) in c-myb expression was also observed between Barrett’s patients (20/42, 48%) and the control groups (9/63, 14%). In the BD patients, 21% (3/14) had increased c-myc mRNA expression compared with none in those with BM (p < 0.05) and BAC. No significant differences in mRNA expression levels were observed between ethnic groups for the genes analysed. In an attempt to determine whether the low expression level of c-myc in the study cohort may be related to possible gene-gene interaction, DNA samples of 199 individuals were subjected to genotyping of the functional GT-repeat polymorphism in the promoter region of the NRAMP1/SLC11A1 gene. Both these genes are involved in iron metabolism and c-myc is known to repress NRAMP1/SLC11A1. Genotype and allele frequencies were similar in all the groups studied with the 3/3 genotype being the most common. However, none of the three above-mentioned BD patients with increased c-myc mRNA expression had the 3/3 genotype. Therefore, although small in number, c-myc-NRAMP1/SLC11A1 interaction may be of adverse significance in patients with allele 2. TP53 mutation analysis was performed on 68 Barrett’s patients, and TP53 immuno-staining on oesophageal biopsy specimens of 55 subjects. Sporadic TP53 mutations were not identified in any of the patients with BM or dysplasia without BAC. Immuno-histochemistry staining of 2+ and 3+ intensity was similar in patients with metaplasia and dysplasia (58%). The low mutation frequency and relative non-specificity of TP53 immunostaining observed in Barrett’s patients seem to preclude its widespread use as a screening tool. TP53 mutation detection may however be useful for risk stratification once dysplasia has been diagnosed, as mutations G245R and D281Y were identified in two patients with BAC. Of the genes studied in the South African population, c-myb represents the most useful marker for early detection of an increased cancer risk in Barrett’s patients. In future, patients with Barrett’s oesophagus may benefit from genetic assessment to complement existing cancer surveillance and treatment strategies.

<p>Adenokarcinom prostate (PCa) je najče&scaron;ći karcinom u mu&scaron;karaca. Intraepitelne prostatične neoplazme visokog gradusa (HGPIN) su lezije koje prethode nastanku invazivnog karcinoma i podrazumevaju kompletno odsustvo bazalnih ćelija i invaziju strome malignim acinusima. Estrogeni receptor &beta; (ER&beta;) se nalazi u jedrima bazalnih i sekretornih ćelija acinusa i delimično u stromalnim ćelijama. Cilj istraživanja je da prikaže i lokalizuje ER&beta; u različitim morfolo&scaron;kim lezijama prostate: hiperplaziji (BHP), PINu i u PCa sa različitim Gleason scorom. Pretpostavlja se da prekancerozne lezije u svojim različitim fazama evolucije ne koreliraju u potpunosti sa ekspresijom ER&beta;. LGPIN pokazuje ekspresiju, dok u HGPINu nema ekspresije. Takođe je pretpostavka da ekspresija ER&beta; postoji u većine srednje diferentovanih PCa, te da se ekspresija posmatranog receptora gubi sa porastom Gleason scora. Ispitivano je pet grupa bolesnika:&nbsp; kontrolna grupa sa BHP i četiri eksperimentalne grupe (PIN i 3 različite grupe PCa). Studija je sprovedena na mu&scaron;karcima različite starosti u periodu 2010&ndash;2012. Nijedan pacijent nije prethodno primio hormonsku terapiju. Sekstant biopsije prostate su bojene na ER&beta; (Novocastra). Lokalizacija i intenzitet ER&beta; ekspresije prikazani su kroz skor: 0 = nula; 1 = &lt;1%; 2 = 1&ndash;10%; 3 = 11&ndash;33%; 4 = 34&ndash;66%; 5 = &gt; 66%. Pozitivni fibroblasti i endotelne ćelije su kori&scaron;ćene za poređenje. Smanjena ekspresija ER&beta; primećena je kod malignih i premalignih lezija prostate naspram BHP. Ekspresija ER&beta; u epitelnim ćelijama acinusa bila je najslabija u dobro diferentovanim PCa. Kod BHP i dobro diferentovanih PCa bila je veća ekspresija ER&beta; u bazalnim ćelijama nego u sekretornim. Lo&scaron;e diferentovani PCa prikazali su smanjenje ekspresije ER&beta; u bazalnim ćelijama. Ukupna ćelijska ekspresija ER&beta; predstavlja složen i ponekad moguće paradoksalan nalaz, na osnovu čega primarni PCa zadržava ekspresiju ovog receptora, ali ipak značajno nižu u poređenju sa benignim epitelom i premalignim lezijama. Ovaj nalaz podupire stanovi&scaron;te o antiproliferativnoj ulozi ER&beta; u tkivu prostate.</p> / <p>Adenocarcinoma of the prostate (PCa) is the most common cancer in men. High-grade prostatic intraepithelial neoplasia (HGPIN) are lesions that precede to invasive carcinomas and include complete absence of basal cells and stromal invasion by malignant acini. Estrogen receptor &szlig;(ER&szlig;) is located in the nuclei of basal and secretory cells and partly in stromal ones.The aim of the research is to describe and localize ER&szlig; in different morphological lesions: prostate hyperplasia (BPH), PIN and PCa with different Gleason score. It is assumed that pre-cancerous lesions in different stages of their evolution not correlate completely with the expression ER&szlig;. LGPIN shows expression, while there is no expression in HGPIN. It is also an assumption that the expression ER&szlig; exists in most medium differentiated PCa, and that the expression of this receptor loses with increasing of Gleason score. Five groups of patient were investigated: control group with BPH and four experimental groups (PIN and 3 different groups of PCa). The study was conducted on men of different ages in the period 2010-2012. None of the patients received prior hormonal therapy. Sextant prostate biopsy were stained on ER&szlig; (Novocastra). ER&szlig; expression is shown through the score: 0 = zero; 1 = &lt;1%; 2 = 1-10%; 3 = 11-33%; 4 = 34-66%; 5 =&gt; 66%. Positive fibroblasts and endothelial cells were used for comparison. Reduced expression was observed in malignant and premalignant lesions of the prostate versus BPH. ER&szlig; expression in the epithelial cells of acini was the weakest in well-differentiated PCa. In BPH and well differentiated PCa was greater expression in the basal cells than in secretory ones. Poorly differentiated PCa showed a decreased ER&szlig; expression in basal cells. Total cellular expression of ER&szlig; is a complex and sometimes paradoxical finding on the basis of which the primary PCa retains expression of this receptor, but significantly lower compared to benign epithelium and premalignant lesions. This finding supports the antiproliferative role of ER&szlig; in prostate tissue.</p>

The Papanicolaou Smear is a screening test which detects premalignant lesions of the uterine cervix. By treating these lesions, cervical cancer can be evaded. In 1988, a cytological diagnosis which communicated a state of uncertainty in the atypicality of cervical cells was first created in the Bethesda Cytology Classification scheme. This diagnosis is now known as atypical squamous cells of undetermined significance (ASC-US) and still little is known about its natural history. / This paper analyzes the results of a longitudinal study incorporating repeated regular measurements of viral and cytological endpoints as well as lifestyle and behavioural aspects, to understand the natural history of an ASC-US Pap smear and identify determinants of ASC-US acquisition and clearance. / Overall, the median duration of ASC-US is short, and is dependent on the definition of clearance since most lesions regress to normal. The factors most predictive of ASC-US acquisition but not clearance relate to HPV infection.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / IntroduÃÃo: HipÃxia constitui em uma caracterÃstica comum de tumores sÃlidos, como em cÃnceres de cabeÃa e pescoÃo, e nessas condiÃÃes, uma via de sinalizaÃÃo envolvendo um regulador de resposta a oxigÃnio, chamado de Fator Induzido por HipÃxia-1 (HIF-1) tem-se destacado, na tentativa de permitir uma melhor compreensÃo sobre a biologia tumoral do cÃncer. Objetivo: Investigar o papel do HIF-1 em carcinoma epidermÃide oral (CEO) e em lesÃes potencialmente malignas que apresentam displasia epitelial oral (DEO). MÃtodos: Estudo observacional, analÃtico e transversal, atravÃs do diagnÃstico e anÃlise imuno-molecular de lesÃes malignas e potencialmente malignas. Foram incluÃdos 10 casos biopsiados com diagnÃstico histopatolÃgico de CEO e 10 casos de DEO. Utilizou-se a tÃcnica imunohistoquÃmica da Estreptoavitina-Biotina com o anticorpo HIF-1 (marca Abcam, diluiÃÃo 1:200, 60 minutos, recuperaÃÃo antigÃnica com citrato pH6 Pascal), analisando 05 campos de cada caso no aumento de 400X. O nÃmero de cÃlulas em cada um dos cinco campos foi somado e considerou-se como unidade amostral o percentual de cÃlulas imuno-positivas para HIF-1&#945; conforme marcaÃÃo nuclear e citoplasmÃtica, bem como intensidade desta Ãltima. Os resultados foram obtidos e comparados entre grupos por meio dos testes t de Student e ANOVA multifatorial, seguido do pÃs-teste de Bonferroni, tomando como base os nÃveis de significÃncia de 5%. Resultados: Foi observado uma expressÃo citoplasmÃtica de HIF-1&#945; em 58.4Â6.0% das cÃlulas epiteliais das DEO e em 77.8Â3.9% das cÃlulas dos CEO, com diferenÃa significante (p=0.022). O percentual de cÃlulas positivas para HIF-1&#945; com marcaÃÃo nuclear tambÃm mostrou diferenÃa significante (p=0.021) entre DEO (0.2Â0.1%) e CEO (2.4Â0.8). NÃo houve diferenÃa significante entre o percentual de cÃlulas com imunomarcaÃÃo positiva fraca em citoplasma entre DEO e CEO (p=0.337), no entanto, houve aumento significante no percentual de cÃlulas com marcaÃÃo citoplasmÃtica moderada (p=0.029) e forte (p=0.031) entre DEO e CEO. ConclusÃo: Foi observada uma aumento da expressÃo, nuclear e citoplasmÃtica, de HIF-1&#945; de DEO para CEO, sugerindo seu envolvimento em estÃgios iniciais da carcinogÃnese oral. RelevÃncia ClÃnica: Buscar o entendimento das complexas vias de sinalizaÃÃo, bem como do microambiente tumoral, e diferentes comportamentos biolÃgicos no cÃncer oral. / Introduction: Hypoxia is a common feature in solid tumors, such as head and neck cancers, and in these conditions a signaling pathway involving a response regulator oxygen, called hypoxia-inducible factor-1 (HIF-1) we have highlighted in an attempt to provide a better understanding of tumor biology of cancer. Objective: To investigate the role of HIF-1 in oral squamous cell carcinoma and premalignant lesions presenting oral epithelial dysplasia. Methods: Observational, analytical and cross through the diagnosis and immuno-molecular analysis of malignant and premalignant lesions. 10 biopsied cases with histopathological diagnosis of the CEO and DEO 10 cases were included. It was used the technique of immunohistochemistry Estreptoavitina-Biotin with HIF-1 antibody (Abcam mark, 1:200 dilution, 60 min pH6 citrate antigen retrieval Pascal) analysis of 05 fields each case at 400X magnification. The number of cells in each of five fields was added and the sample was considered as a unit the percentage of positive cells immuno-HIF-1&#945; nuclear and cytoplasmic as well as intensity thereof. The results were obtained and compared between groups by the Student and multifactor ANOVA followed by Bonferroni post-test t test, based on the significance levels of 5%. Results: Cytoplasmic expression of HIF-1&#945; was observed in 58.4 Â 6.0% of the epithelial cells of the DEO and 77.8 Â 3.9% of the cells of the CEO, with a significant difference (p = 0.022). The percentage of cells positive for HIF-1&#945; nuclear staining also showed significant difference (p = 0.021) between DEO (0.2 Â 0.1%) and CEO (2.4 Â 0.8). There was no significant difference between the percentage of cells with weak positive immunostaining in the cytoplasm between DEO and CEO (p = 0.337), however, a significant increase in the percentage of cells with moderate cytoplasm staining (p = 0.029) and strong (p = 0.031) between DEO and CEO. Conclusion: One increasing the expression, nuclear and cytoplasmic HIF-1&#945; DEO to CEO was observed, suggesting their involvement in the early stages of oral carcinogenesis. Clinical Relevance: Seek understanding of the complex signaling pathways, as well as the tumor microenvironment, and different biological behaviors in oral cancer.

Orientador: Marcio Ajudarte Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-17T15:24:01Z (GMT). No. of bitstreams: 1 Gouvea_AdrieleFerreira_D.pdf: 1529519 bytes, checksum: 67d58c675522b5dd769d5fcad163d152 (MD5) Previous issue date: 2011 / Resumo: Leucoplasia verrucosa proliferativa (LVP) tem como principais características acometer principalmente mulheres, com idades acima dos 60 anos, sem hábitos nocivos, com lesões multifocais, recorrentes após excisão e com altas taxas de malignização. Alguns estudos com proteínas que podem estar envolvidas no controle do ciclo celular, incluindo Mcm2 e geminina, e análise de ploidia do DNA têm sido realizados com o objetivo de identificar lesões com maior predisposição para transformação maligna. Objetivos: Determinar a correlação das características clinicopatológicas de 21 pacientes com diagnóstico de LVP a seu estado de ploidia do DNA e expressão de Ki-67, Mcm2 e geminina. Métodos: 65 amostras de biópsia de 21 pacientes com LVP e 12 amostras de mucosa oral normal foram coletados, feitas imunoistoquímicas para ki-67, Mcm2 e geminina e realizada a análise da ploidia do DNA utilizando citometria de imagem (ACIS III); Resultados: Relação mulher: homem foi de 6:1 e a média de idade foi 65,5 anos. Dos 21 casos, 17 (80,96%) não reportaram fumo ou consumo de bebidas alcoólicas. Transformação maligna foi observada em nove pacientes (42,86%), em um tempo de seguimento clínico de 7,38 anos. Dos 21 pacientes, vinte tiveram seu DNA analisado por citometria de imagem e aneuploidia foi encontrada em 95,24% dos casos. A freqüência e severidade da aneuploidia e valores médios do índice de heterogeneidade (HI) aumentaram de acordo com o aumento das anormalidades epiteliais (p<0.0001), assim como as frações excedentes de 5n (p=0.0007). Os casos que desenvolveram carcinoma não apresentaram status aneuplóide mais grave do que as outras amostras (a maioria foi moderadamente aneuplóide). Em cinco casos as biópsias iniciais apresentando hiperqueratose e acantose ou displasia leve mostraram status aneuplóides e progrediram para carcinoma (55,5%). Não houve correlação entre os graus de displasia e a expressão de das diferentes proteínas estudadas, exceto para Mcm2 (p= 0.0317). Conclusões: Estes achados associados aos altos índices de anormalidades na ploidia do DNA podem contribuir para previsão de áreas com chances de malignização e suportam a afirmação de que LVP é uma entidade de fato distinta. / Abstract: Proliferative verrucous leukoplakia (PVL) presents as main characteristics: affects mostly women, with ages over 60 years, not presenting harmful habits; presence of multifocal lesions, recurrent after excision, with high malignization rates. Some studies with proteins that may be involved in the cell cycle control, including Mcm2 and geminin, and DNA ploidy analyzis has been performed aiming to identify lesions with a greater predisposition to malignant transformation. Objectives: To determine the correlation of the clinicopathological features of 21 PVL patients with their DNA ploidy status and Mcm2, geminin and Ki-67 expression. Methods: 65 biopsy specimens of 21 PVL patients and 12 normal oral mucosa were collected; immunohistochemistry to Mcm2, geminin and ki-67 and DNA ploidy analysis using image based citometry (ACIS III) were performed. Results: Female: male ratio was of 6:1 and the average age was 65.5 years. Of the 21 PVL cases, seventeen (80.96%) did not report smoking or alcoholic habit. Malignant transformation was observed in nine patients (42.86%). Of the 21 patients, twenty had the DNA examined by an image-based cytometry and aneuploidy was found in 95.24% of the cases. The frequency and severity of aneuploidy and the mean values of DNA HI increased according to the epithelial abnormality (p<0.0001), as well the 5n exceeding fractions (p=0.0007). Cases that developed carcinoma did not presented higher ploidy status compared to the other samples (the majority was moderately aneuploidy). In five cases (55.5%), initial biopsies presenting hyperkeratosis and acanthosis or mild dysplasia showed aneuploid status and latter developed carcinoma. There was no correlation between the grades of dysplasia and the LI of different immunohistochemically studied proteins, except for Mcm2 (p= 0.0317). Conclusions: This finding associated to the high incidences of DNA ploidy abnormalities may contribute to predict areas prone to malignant transformation and to support the hypothesis that PVL is a distinct entity. / Doutorado / Patologia / Doutor em Estomatopatologia

No description available.

<p>Osobe kojima su transplantirani organi imaju povećan rizik pojave malignih oboljenja, među kojima dominiraju maligni tumori kože. Smatra se da je osnovni razlog primena imunosupresivne terapije, ali jo&scaron; nije sasvim jasan mehanizam i nivo dejstva različitih imunosupresiva. Važan uticaj na nastanak većine malignih tumora kože ima ultraljubičasto (UV) zračenje koje izaziva pojačano starenje kože u vidu histolo&scaron;ki prepoznatljivog fotoo&scaron;tećenja, sa odlikama razvoja elastoze i limfocitne infiltracije. U na&scaron;oj zemlji do sada nisu sprovođena istraživanja rizika pojave maligniteta kože kod transplantiranih pacijenata, ne postoje podaci o njihovoj incidenci, uticaju imunosupresivne terapije i drugim potencijalnim faktorima rizika. U dostupnoj literaturi nema objavljenih radova iz oblasti analize histolo&scaron;kog fotoo&scaron;tećenja kože kod osoba na imunosupresivnoj terapiji. Ciljevi ove studije preseka bili su utvrđivanje učestalosti, vrste i lokalizacije premalignih i malignih lezija kože kod pacijenata nakon transplantacije bubrega, povezanosti njihove pojave sa dužinom, vrstom i režimom primene imunosupresivne terapije i sa histolo&scaron;ki verifikovanim fotoo&scaron;tećenjem perilezionalne kože. U studiju je uključeno 66 pacijenata kojima je transplantiran bubreg (primaoci organskog transplantata &ndash; POT). Relevantni podaci su prikupljeni putem upitnika i iz medicinske dokumentacije, kliničko-dermoskopskim pregledom kože uočene suspektne lezije su bioptirane u cilju postavljanja dijagnoze i utvrđivanja histolo&scaron;kih parametara fotoo&scaron;tećenja, a u studiju su uključeni i maligni tumori kože POT ispitanika uklonjeni u periodu od prethodnih 5 godina ali nakon transplantacije. Radi komparacije prisutnih faktora rizika i stepena fotoo&scaron;tećenja kože sa op&scaron;tom populacijom formirana je kontrolna grupa (KG) ispitanika kojima je prethodno bioptirana koža, bez oboljenja bubrega i bez imunosupresije, slična po polu i životnoj dobi sa onim POT ispitanicima kojima je urađena biopsija. Za svaku leziju iz POT grupe obezbeđene su po 2 lezije iz KG, tako da je pojedinim ispitanicima POT grupe analizirano vi&scaron;e lezija, dok je u KG 1 ispitanik &ndash; 1 lezija. Osnovno oboljenje bubrega do započinjanja dijalize kod ispitanika POT grupe prosečno je trajalo 7,67 godina, u strukturi oboljenja bubrega dominirao je hronični glomerulonefritis sa 31,8%, a ispitanici su na dijalizi bili prosečno 4,54 godine. Prosečna životna dob ispitanika u momentu transplantacije iznosila je 42,5 godina, 60,6% imalo je isključivo kadaveričnu transplantaciju, a prosečno trajanje jatrogene imunosupresije iznosilo je 4,89 god. U POT grupi bioptirane su 33 lezije, među kojima su od značaja za studiju bile 2 (6,1%) aktinične keratoze (AK), 3 (9,1%) displastična nevusa (DN), 1 (3,0%) melanom (MM), 3 (9,1%) skvamocelularna karcinoma (SCK) i 6 (18,2%) bazocelularnih karcinoma (BCK). U POT grupi učestalost MM bila je 1,5%, učestalost SCK 4,5%, učestalost BCK 9,1%, dok je utvrđeni relativan rizik pojave MM u POT populaciji 227 puta veći, BCK 316 puta veći, a SCK 805 puta veći nego u op&scaron;toj populaciji. Relativan rizik nastanka AK i DN nije određen zbog izostanka zvanične registracije u op&scaron;toj populaciji. POT grupa i KG nisu se statistički značajno razlikovale po Ficpatrikovom fototipu kože, profesionalnoj izloženosti UV zračenju, upotrebi solarijuma, broju solarnih opekotina, ličnoj anamnezi malignih tumora kože i konzumiranju cigareta. Pripadnici KG su se značajno vi&scaron;e rekreativno izlagali UV zračenju, če&scaron;će koristili sredstva za za&scaron;titu od sunčevog zračenja, če&scaron;će imali bliske srodnike sa malignim tumorima kože, če&scaron;će konzumirali alkohol, značajno veći broj ispitanika KG imao je pregled kompletne kože i informaciju o merama prevencije od strane lekara, dok 50% ispitanika POT grupe nije znalo da su pod povećanim rizikom pojave maligniteta kože. U stepenu elastoze među grupama nije postojala statistički značajna razlika, dok je limfocitna infiltracija bila marginalno izrazitija u POT grupi bez obzira na vrstu lezije. U POT grupi utvrđena je statistički značajna povezanost prisustva malignog tumora sa većim stepenom perilezionalne limfocitne infiltracije i elastoze. U KG utvrđena je statistički značajna povezanost prisustva malignog tumora sa većim stepenom limfocitne infiltracije, dok nije bilo statistički značajne razlike u stepenu perilezionalne elastoze. U studiji je utvrđeno da osobe nakon transplantacije bubrega imaju statistički značajno veći rizik nastanka BCK, SCK i MM kože u odnosu na op&scaron;tu populaciju, sa najče&scaron;ćom lokalizacijom ovih tumora u predelu glave. Dužina primene imunosupresivne terapije uop&scaron;teno nije statistički značajno uticala na pojavu premalignih i malignih tumora kože, ali je kumulativna doza pojedinih imunosupresiva poput ciklosporina i azatioprina imala statistički značajan uticaj na pojavu premalignih i malignih lezija kože. Dužina imunosupresije je statistički značajno uticala na stepen elastoze, ali je imala marginalan uticaj na stepen perilezionalne limfocitne infiltracije.</p> / <p>Organ transplant recipients are at an increased risk of developing malignancies, with the predominance of malignant skin tumors. The main cause is considered to be the administration of immunosuppressive therapy, but the mechanism and effect levels of different immunosuppressive agents are still not completely clear. Ultraviolet (UV) rays also influence the development of malignant skin tumors, causing increased skin aging with histologically recognisable photo damage, with its hallmark being development of elastosis and lymphocytic infiltration. No research on the topic of risks of malignant skin tumors in transplant patients has been done in our country, there is no data on their incidence, or on the effects of immunosuppressive agents and other potential risk factors. There are also no published studies in the field of hystological photo damage analysis in patients on immunosuppressive therapy. The aims of this study were to establish the rates of occurance, types and localisation of premalignant and malignant skin lesions in kidney transplant recipients (KTR) and to associate their advent with the length, type and regimen of immunosuppressive therapy. A total of 66 KTR patients were enrolled in the study. Relevant information was gathered through a specially constructed questionnaire and from the medical records, followed by combined clinical and dermoscopic skin examination to detect suspicious lesions which were biopsied in order to determine the histopathologic diagnosis of the lesion and perilesional degree of photo damage. The study also encompassed malignant skin tumors of KTR patients that have been removed in the last 5 years, but after the transplantation. For the sake of comparison of the risk factors and the levels of photo damage with the general population, an age and sex - matched control group (CG) of patients with previous skin biopsy but without kidney disease and immunosuppression was formed. For each lesion from KTR group, 2 lesions from CG were provided, meaning that some KTR patients had several lesions analysed, whereas in the CG only 1 lesion per patient was analyzed. The average duration of underlying kidney diseases in KTR was 7,67 years, the most frequent being chronic glomerulonephritis (31,8%), and an average duration of dialysis was 4,54 years. The mean age at transplantation was 42,5 years, with 60,6% of the KTR having exclusively cadaveric graft. The mean duration of the iatrogenic immunosuppression was 4,89 years. In the KTR group a total of 33 lesions were biopsied, 2 of which were actinic keratoses (AK) (6,1%), 3 were dysplastic nevi (DN) (9,1%), 1 melanoma (MM) (3,0%), 3 squamous cell carcinomas (SCC) (9,1%) and 6 basal cell carcinomas (BCC) (18,2%). The estimated frequency of MM was 1,5%, SCC 4,5%, BCC 9,1%, and the estimated relative risk of MM in KTR being 227, BCC 316, and SCC 805 times higher compared to the general population. The relative risk of AK and DN development could not have been estimated as there are no official records in the general population. The KTR and CG were not significantly different judging by the Fitzpatrick skin phototype, occupational UV exposure, sunbed usage, personal history of skin cancers, or smoking. The controls were recreationally more exposed to UV rays, used sun protective measures more frequently, had more relatives with skin cancers and consumed alcohol more frequently. A significantly greater number of controls had had complete skin examination and protective measures counceling by the doctor, while 50% of KTR patients did not even know that they were at an increased risk of malignant skin tumor development. There was no significant difference in elastosis levels among the groups, whereas the lymphocitic infiltration was only marginally greater in the KTR group. A significant association between the level of perilesional photodamage and developement of malignant tumors was estimated for the KTR group, whereas in the CG only the perilesional lymphocitic infiltration was strongly associated to malignant lesions. The study results suggest that KTR patients have a significantly higher risk of BCC, SCC and MM development in comparison with the general population, the most common localisation being in the head region. The duration of the immunosuppressive therapy had no significant effect on the premalignant and malignant tumors development, whereas the cummulative dose of certain immunosuppressives (such as cyclosporine and azathioprine) affected the development notably. The duration of immunosuppression statistically influenced the elastosis levels, but had only a marginal influence on the perilesional lymphocitic infiltration levels.</p>

<p>UVOD: Kolorektalni karcinom je na trećem mestu po učestalosti oboljevanja od svih karcinoma uz porast incidencije CRC u visoko razvijenim zemljama.70% obolelih od CRC je starije od 65 godina uz veću incidenciju proksimalnih karcinoma u odnosu na distalne u svim uzrasnim grupama i kod oba pola. Smatra se da bi 66-75% slučajeva CRC moglo biti izbegnuto zdravim načinom života. 75% CRC nastaje iz adenomatoznih preko polip kancer sekvence i da vi&scaron;e od 90% adenoma neće progredirati u karcinom. U studijama skrining kolonoskopija prijavljeno je 6-12% neviđenih velikih polipa i ko 5% CRC na inicijalnom kolonoskopskom pregledu. Postoperativne periodične kolonoskopije nakon operacije kolorektalonog karicinoma imaju za cilj otkrivanje metahronih carcinoma polipa kao pojavu bolesti na anastomozi ali nije dokazani benefit u preživljavanju bolesnika koji su imali učestalije postoperativne kolonoskopije (na godinu dana) u odnosu na one koji su praćenina 3 ili 5 godina. CILJEVI ISTRAŽIVANJA: Prospektivno ispitivanje pojave intervalnih lezija kolona (malignih i premalignih) u periodu od 2-7 godine od prve negativne kolonoskopije bez obzira na razlog pregleda. Ispitivanje razlike u životnim navikama između ispitanika u zavisnosti od nalaza na ponovljenoj kolonoskopiji. Retrospektivna analiza svih dijagnostičkih i kontrolnih kolonoskopija. MATERIJAL I METODE: Ponavljana je kolonoskopija kod ispitanika koj su na dijagnostičkim kolonoskopijama rađenim na Institutu za onkologiju Vojvodine u periodu 2005-2011. imali uredan kolonoskopski nalaz. Od 160 pozvanih ispitanika na ponovnu kolonoskopiju se odazvalo 64 ispitanika a 151 ispitanik je popunio upitnik o životnim navikama. Urađena je i retospektivna analiza 2750 dijagnostičkih kolonoskopija. Analizirani su rezultati 1064 prvih postoperativnih kolonoskopija kao i nalazi sa 1147 ponovljenih kolonoskopija kod ispitanika operisanih od kolorektalnog carcinoma koji su imali uredan nalaz na prvoj kolonoskopiji. REZULTATI: Od 160 pozvanih ispitanika,njih 64 (42,3%) se odazvalo na ponovni pregled (45 žena i 19 mu&scaron;karaca) prosečne starosti60,13 godina. Kod 15 ispitanika(24.3%) nađeno je ukupno 22 polipa (10 žena i 5 mu&scaron;karaca) bez statistički značajne razlike u pozitivnosti nalaza u odnosu na pol (x2test; x2=0,014; p=0,904) i pozitivnu porodičnu anamnezu (x2test; x2=0,125; p=0,724). 12 slucajeva (14,06%) su bili polipi visokog rizika: 5 (41.6%) lokalizovano u proksimalnom kolonu i 7 (58.3% ) u distalnom kolonu. Nije dijagnostikovan nijedan intervalni karcinom. Nije dokazana statistički značajna razlika u pozitivnosti nalaza na ponovljenoj kolonoskopiji u odnosu na razmak posmatran u grupama do 3 i do 5 godina od predhodne kolonoskpije (x2test; x2=0,020; p=0,887) niti ukoliko se posmatra po grupama do 5 i preko 5 godina od negative kolonoskopije (x2test; x2=3,082; p=0,079). Nema statistički značajne razlike u pozitivnosti nalaza na ponovljenoj kolonoskopiji u odnosu na to da li su pacijenti konzumiraju alkohol ili ne (x2test; x2=0,113; p=0,911) kao i u odnosu na to da li su pacijenti imali redovnu fizičku aktivnost (x2test; x2=0,476; p=0,490). Na dijagnostičkim kolonoskopijama je uočena statistički značajna razlika u uzrastu pacijenata u zavisnosti od razloga kolonoskopije (F=7,111; p=0,000) kod pacijenata kod kojih su dijagnostikovani polipi. Oni sa pozitivnom porodičnom anamnezom i polipima su statistički značajno mlađi u odnosu na ostale osim onih koji su se na pregled javili zbog bola u trbuhu poremećaja ritma stolice. Nije bilo statistički značajne razlike po polu, uzrastu, u razlogu kolonoskopije kod osoba sa dijagnostikovanim polipima. Statistički je značajniji broj žena sa lokalizacijom polipa u distalnom delu debelog creva u odnosu na proksimalni (x2test; x2=18,495; p=0,000). Kod mlađih uzrasnih grupa statistički značajnije su zastupljeni polipi u rektumu(x2test; x2=79,963; p=0,000). Ispitanici sa proksimalnom lokalizacijom polipa imaju 1,724 puta veću &scaron;ansu za adenome visokog rizika u odnosu na one sa distalnom lokalizacijom. Nema statistički značajne razlike u distribuciji karcinoma u odnosuna pol (x2test; x2=3,2110; p=0,201). Na 1064 prvih postoperativnih kolonoskopija je bilo ukupno 346 (32,5%) pozitivnih nalaza. Dijagnostikovano je 60 karcinoma od kojih je 43,3 % lokalizovano na anastomozi a kod 286 ispitanika nađeno je ukupno 546 polipa. Mu&scaron;karci statistički značajnije če&scaron;će imaju pozitiva nalaz (x2 test; x2=17,252; p=0,000). Bonferroni post hoc testom je utvrđeno da su polipi proksimalne lokalizacije statistički značajno veći od onih u rektumu (p=0,043). Na kontrolnim kolonoskopijama rađenim u cilju praćenja nakon resekcije kolorektalnog karcinoma multivarijatnom analizom ( pol, uzrast i vreme od operacije) utvrđeno je da mu&scaron;karci imaju 1,4 puta veću &scaron;ansu (OR=1,457) od žena za pojavu promena (polipa i karcinoma).Ispitanici kod kojih je od operacije pro&scaron;lo od 3 do 5 godina imaju 1,6 puta veću &scaron;ansu za pojavu promene u odnosu na one kod kojih je pro&scaron;la 1 godina (OR=1,605). ZAKLJUČAK: Kod 24.3% pregledanih ispitanika dijagnostikovani su polipi(jedan hipeplastičnii 21 adenoma ). 14,06% svih polipa je imalo karakteristike polipa visokog rizika bez statistički značajne razlike u pojavi polipa kod ispitanika kod kojih je pregled rađen 3,5 ili nakon 5 godina od prve negativne kolonoskopije. Nije dijagnostikovan niti jedan karcinom &scaron;to znači da nema potrebe za ponavljanjem kolonoskopija u kraćem vremenskom intervalu od unapred planirane kolonoskopije kod ispitanika koji su imali uredan inicijalni kolonoskopski nalaz &scaron;to se odnosi i na ponavljane kolonoskopije kod ispitanika operisanih od CRC-a. Na dijagnostičkim kolonoskopijama statistički značajniji broj žena sa lokalizacijom polipa u distalnom delu debelog creva u odnosu na proksimalni i nije zapažena razlika u distribuciji karcinoma u odnosu na pol i uzrast ispitanika.</p> / <p>INTRODUCTION:Colorectal cancer is the third most frequent illness of all carcinomas with an increase in the incidence of CRC in highly developed countries. 70% of patients with CRC are older than 65 years with higher incidence of proximal cancers compared to distal in all age groups and in both sexes. It is believed that 66-75% of CRC could be avoided through healthy lifestyle. 75% of CRC arise from adenomatous polyp cancer via sequences, and that more than 90% of adenoma will not progress to carcinoma. In studies of screening colonoscopy was reported 6-12% of unobserved large polyps and approximately 5% of the CRC on the initial colonoscopy.Postoperative periodic colonoscopy after colorectal cancer surgery aim to detect metachronous cancer and polyps and disease occurrence anastomoses but not proven survival benefit in subjects who had more frequent postoperative colonoscopy (per year) compared to those who were followed for 3 or 5 years. AIM:Prospective study of interval colon lesions occurrence (malignant and pre-malignant) in the period from 2-7 years after initial negative colonoscopy regardless of the reason for the check. Test of differences in lifestyle between subjects depending on the findings of the repeated colonoscopy.A retrospective analysis of all the diagnostic and control colonoscopy. METHODOLOGY: Repeated colonoscopy in subjects who are at-made diagnostic colonoscopy at the Oncology Institute of Vojvodina in the period 2005-2011 had normal colonoscopy findings. Of the 160 subjects invited to re colonoscopy for review responded 64 subjects and 151 subjects filled out a questionnaire about life habits. Retrospective analysis of 2750 and diagnostic colonoscopy has been done. Results of the 1064 first postoperative colonoscopy and results of the 1147 repeated colonoscopy in patients operated on for colorectal cancer that had normal findings on the first colonoscopy has been analyzed. RESULTS:Of the 160 invited subjects, 64 of them (42.3%) responded to the repeated review (45 women and 19 men), mean age 60.13 years. In 15 subjects (24.3%) found a total of 22 polyps (10 women and 5 men) with no statistically significant differences in positivity findings in relation to sex (x2test; x2 = 0.014; p = 0.904) and a positive family anamnesis (x2test; x2 = 0.125; p = 0.724).12 cases (14.06%) were high risk of polyps: 5 (41.6%) localized in the proximal colon, and 7 (58.3%) in the distal colon. Not a single interval cancer diagnosed. There was no statistically significant difference in positivity findings with repeated colonoscopy in relation to the distance observed in groups of 3 to 5 years from the previous colonoscopy (x2test; x2 = 0.020; p = 0.887) or when observed in groups up to 5 and over 5 years of negative colonoscopy (x2test; x2 = 3.082; p = 0.079). No statistically significant differences in positivity findings with repeated colonoscopy in relation to whether the patients consume alcohol or not (x2test; x2 = 0.113; p = 0.911) as well as in relation to whether patients are regularly exercising (x2test; x 2 = 0.476; p = 0.490). Statistically significant difference is confirmed in the age of patients at the diagnostic colonoscopy, depending on the reason for colonoscopy (F = 7.111; p = 0.000) in patients who were diagnosed polyps. Those with a family anamnesis and polyps were statistically significant younger in comparison to others except those who have come forward for review because of abdominal pain and bowel movement rhythm disturbances.There were no statistically significant differences by sex, age, the reason for colonoscopy in patients diagnosed with polyps.Statistically is more significant number of women with the localization of polyps in the distal part of the colon comparing to the proximal (x2test; x2 = 18,495; p = 0.000).In younger age groups are represented statistically significant polyps in the rectum (x2test; x2 = 79.963, p = 0.000). Subjects with proximal localization of polyps are 1,724 times more likely for high-risk adenomas compared to those with distal localization.No statistically significant differences in the distribution of cancer in relation to sex (x2test; x2 = 3.2110; p = 0.201).On the first postoperative colonoscopy in 1064 subjects there were a total 346 (32.5%) positive findings. 60 carcinoma diagnosed of which 43.3% is localized on the anastomosis and in 286 of the subjects had a total of 546 of the polyps.Men statistically significantly more likely to have positive findings (x2 test; x2 = 17,252; p = 0.000). Bonferroni post hoc test showed that polyps proximal localization significantly bigger than those in the rectum (p = 0.043). On the control colonoscopy-made for the purpose of monitoring after resection of colorectal cancer by multivariate analysis (sex, age and time of surgery) it has been found that men are 1.4 times more likely (OR = 1.457) than women for the occurrence of changes (polyps and cancers).Subjects having passed since the operation of 3 to 5 years are 1.6 times more likely to develop a change with respect to those in which the more than one year elapsed (OR = 1.605). CONCLUSION:In 24.3% subjects were diagnosed polyps (one hyperplastic and 21 adenomas).14.06% of all polyps had the characteristics of high-risk polyps with no statistically significant difference in the occurrence of polyps in subjects where the examination was done after 3,5 or 5 years since the first negative colonoscopy. No cancers diagnosed, meaning there is no need to repeat colonoscopy in a shorter period of time than pre-planned colonoscopy in subjects who had normal initial colonoscopy findings which refers to the repeated colonoscopies in subjects operated on for CRC.For diagnostic colonoscopy statistically significant number of women with the localization of polyps in the distal part of the colon compared to proximal and was not observed differences in the distribution of carcinoma in relation to sex and age of the subject.</p>