Comparação da sobrevivência e dos fatores prognósticos em pacientes com adenocarcinoma gástrico T2 e T3

OBJETIVO: Comparar a sobrevivência e os fatores prognósticos, após o tratamento cirúrgico de pacientes com adenocarcinoma gástrico que compromete a camada muscular própria (T2), e de pacientes cujo tumor invade a subserosa (T3). MÉTODOS: Estudo retrospectivo de 122 pacientes com câncer gástrico invadindo a muscular própria e subserosa, submetidos ao tratamento cirúrgico no período de janeiro de 1997 a dezembro de 2008 e acompanhados até dezembro de 2010. Foram analisadas variáveis demográficas, cirúrgicas e anatomopatológicas. RESULTADOS: Dos 122 pacientes, 22 (18%) foram excluídos da análise final porque apresentaram: margem positiva, mortalidade pós-operatória, segundo tumor primário e menos de 15 linfonodos na peça cirúrgica. Entre os 100 pacientes incluídos, 75 apresentavam tumores com invasão da muscular própria (T2) e 25 com invasão da subserosa (T3). A sobrevivência global foi 83,8%, sendo 90,6% no T2 e 52,1% no T3. Na análise univariada apresentaram significância: metástase linfonodal (p=0,02), tamanho do tumor (p=0,000), estadiamento patológico do tumor (p=0,000), estadiamento patológico linfonodal (p=0,000) e estadiamento por grupos da classificação TNM-UICC/AJCC, 2010 (p=0,000) Na análise multivariada, os fatores prognósticos independentes foram o tamanho do tumor e o estadiamento patológico linfonodal (pN). CONCLUSÃO: O comprometimento linfonodal e o tamanho do tumor são fatores prognósticos independentes nos tumores com invasão da muscular própria e nos tumores com invasão da subserosa. O T2 apresenta menor tamanho, menor taxa de linfonodos metastáticos e consequentemente, melhor prognóstico que o T3.

Qualidade de vida de doentes esofagectomizados: adenocarcinoma versus carcinoma epidermoide

OBJETIVO: Avaliar e comparar a qualidade de vida de pacientes esofagectomizados para tratamento de adenocarcinoma da junção esofagogástrica e de carcinoma epidermoide. MÉTODOS: estudo transversal no pós-operatório de doentes esofagectomizados por adenocarcinoma da junção esofagogástrica (Adenoca) e carcinoma epidermóide (CEC), empregando o questionário SF-36 aplicado em 24 pacientes (10 por Adenoca e 14 por CEC), a partir do 5º mês de pós-operatório, incluindo os sintomas clínicos e a variação de peso. RESULTADOS: A avaliação da QV mostrou melhor resultado de capacidade funcional (p=0,018) para o grupo Adenoca. Houve correlação entre os domínios "saúde mental" e "limitação por aspectos emocionais" (p=0,003) e entre "dor" e "limitação por aspectos físicos" (p=0,003) nos dois tipos histológicos. A perda de peso foi maior nos esofagectomizados por Adenoca (45,9Kg), sem diferença significativa entre o IMC atual (p>0,66). A disfagia foi relatada por 83,3% dos pacientes, a anorexia por 58,3%, a dificuldade de mastigação por 42%, a náuseas e os vômitos por 41,7% e a diarréia por 29,2%, sem correlação com a QV relatada (p>0,05). CONCLUSÃO: O escore mais alto para capacidade funcional indica que o paciente com Adenoca foi capaz de realizar todo tipo de atividade física, incluindo as mais vigorosas em um nível maior que o paciente com CEC. Alguns sintomas persistiram no pós-operatório, porém não interferiram na qualidade de vida dos pacientes.

Síndrome de estenose pilórica por adenocarcinoma de piloro

We present a case of primary malignant pylorus neoplasia, emphasizing its rarity, the difficulty of diagnosis and the importance of an adequate prepare before the endoscopic procedure. Literature shows that tumors compromising the first, third and fourth segments of duodenum are rare, especially those of the pyloric area, representing only 0.35% of all malignant tumors of the gastrointestinal tract. Adenocarcinoma is the most common histological type, representing 50% of all malignant neoplasias at this site. The most common symptoms are weight loss, nausea, vomiting, abdominal pain, abdominal mass, sudden changes in intestinal habits and iron deficiency anemia secondary to chronic intestinal hemorrhage. Survival after five years is only 18%. We report a case of a seventy-one year-old male referring early satiety, epigastric pain, retrosternal burning and dyspepsia, with unspecific results in complementary exams, since complete gastric emptying was not achieved. As symptoms worsened, the patient was submitted to laparotomy, with identification of gastric dilation and severe pyloric stenosis, macroscopically suggesting malignancy. The chosen procedure was a subtotal gastrectomy. Adjuvant radiotherapy and chemotherapy were not used. The patient is been followed-up without tumor recurrence so far.

Adenocarcinoma de Células Claras de Endocérvice em Menina de 7 anos

O adenocarcinoma de células claras de colo e vagina em adolescentes é uma doença rara e na maioria das vezes associada com o uso do dietilestilbestrol (DES) durante a gestação. A queixa mais freqüente é o sangramento vaginal irregular que pode ser incorretamente interpretado como vaginite nas crianças e como alterações do eixo hipotálamo-hipófise nas adolescentes. Relatamos o caso de adenocarcinoma de células claras de endocérvice em uma menina de 7 anos de idade atendida no Ambulatório de Ginecologia da Infância e Adolescência, e chamamos a atenção para o diagnóstico de câncer genital que, embora raro nesta faixa etária, deve ser cogitado quando deparamos com sangramento genital em crianças.

Freqüência de Adenocarcinoma de Endométrio em Ambulatório de Histeroscopia: Um Estudo Multicêntrico

Objetivo: realizar um censo sobre a freqüência do adenocarcinoma de endométrio em mulheres submetidas a histeroscopia diagnóstica em cinco serviços brasileiros de vídeo-endoscopia ginecológica localizados em São Paulo, Rio de Janeiro, Salvador, Caxias do Sul e Porto Alegre. Métodos: foram utilizados questionários padronizados com o objetivo de obter as informações sobre a presença de adenocarcinoma, acometimento da cavidade uterina e tipo histológico nos exames histeroscópicos de mulheres na pré e pós-menopausa. Resultados: entre os 6.466 procedimentos histeroscópicos realizados, foi diagnosticado adenocarcinoma de endométrio em 92 pacientes (1,4%), sendo este diagnóstico confirmado pela histologia em 79 casos (1,2%). Para o diagnóstico histeroscópico de adenocarcinoma de endométrio, confirmado por exame histológico, obtivemos sensibilidade de 85,9%, especificidade de 100%, valor preditivo positivo de 100% e valor preditivo negativo de 98,6%. No grupo de 3.845 pacientes na pré-menopausa, o carcinoma foi diagnosticado pela histeroscopia em 9 (0,2%) casos e confirmados pela histologia em 8 (0,2%), ao passo que no outro grupo de 2.621 pacientes na pós-menopausa, a histeroscopia diagnosticou adenocarcinoma em 83 (3,2%) pacientes, dos quais 71 casos (2,7%) foram confirmados pela histologia. Conclusões: este estudo alerta para uma maior preocupação em relação ao câncer de endométrio, especialmente na pós-menopausa, revelando a necessidade de haver mais estudos epidemiológicos para que se possam elaborar programas de prevenção e diagnóstico precoce do adenocarcinoma de endométrio.

Adenocarcinoma viloglandular de cérvice uterina

OBJETIVO: o adenocarcinoma viloglandular (AVG) da cérvice foi identificado como uma variante do adenocarcinoma cervical que ocorre em mulheres jovens e traz um excelente prognóstico. Diante da escassez de estudos relacionados ao tema, nós relatamos seis casos de AVG de cérvice. MÉTODOS: acompanhamos a evolução de seis casos de AVG, no período de 1995 a 2006, no Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUC-RS). Coletamos informações clínicas e histológicas de todas as pacientes e submetemos todas as peças cirúrgicas para revisão histológica. RESULTADOS: a idade média da apresentação foi de 43,5 anos (variando de 27 a 61 anos). Quatro pacientes submeteram-se à histerectomia radical de Wertheim-Meigs e linfadenectomia pélvica bilateral, uma submeteu-se a conização e subseqüente radioterapia e uma a linfadenectomia pélvica seguida de radioterapia. Todas as pacientes estão vivas e bem, sem evidência de recorrência. CONCLUSÕES: as implicações da terapia são discutidas. Propomos aqui a inclusão do estudo do padrão de envolvimento linfovascular na determinação diagnóstica do AVG. Assim, ao referenciarmos este diagnóstico, poderemos optar, com cautela, pela terapia conservadora, salvo particularidades de cada caso.

Colpocitologia de mulheres com diagnostico de adenocarcinoma do colo do utero

OBJETIVO: Analisar os achados citológicos de mulheres detectadas com adenocarcinoma do colo do útero, levando em conta o histórico da paciente no ano que antecedeu ao diagnóstico e a histopatologia das lesões. MÉTODOS: Este é um estudo comparativo, retrospectivo conduzido com dados de mulheres com adenocarcinoma ou com carcinoma escamoso do colo do útero detectados entre 2002 e 2008. Os laudos da citologia foram sintetizados de acordo com a terminologia Bethesda revisada em 2001 e foram comparados com a histopatologia de adenocarcinoma e de carcinoma escamoso. Foram verificadas as distribuições dos achados citológicos, a concordância global e corrigida pelo acaso com o uso do coeficiente Kappa de Cohen. Para isso, as alterações citológicas foram agregadas de acordo com a origem epitelial, formando os grupos de células glandulares e de células escamosas, tendo como padrão ouro os grupos de tumor histopatologicamente confirmados (adenocarcinoma versus carcinoma escamoso). RESULTADOS: No período, 284 casos de câncer do colo uterino foram diagnosticados. Os casos efetivamente estudados compreenderam 27 e 54 pacientes com adenocarcinoma e com carcinoma escamoso, respectivamente. O grupo de adenocarcinoma representou 9,5% do total diagnosticado, com 56% das mulheres com idade inferior a 50 anos. A coleta da citologia foi feita em média 92 dias antes do diagnóstico do câncer (variação: 19 dias a 310 dias). Em 41,6% dos casos, a citologia que precedeu o diagnóstico do adenocarcinoma foi indicativa de alterações glandulares do tipo adenocarcinoma e atipias de células glandulares. A concordância simples foi de 73,7% e o coeficiente Kappa de 48,7%, sugerindo moderada concordância. CONCLUSÃO: Nesta população, a citologia teve um importante papel no rastreio de mulheres com adenocarcinoma, embora algumas delas tenham sido referidas para esclarecer sintomas clínicos. A concordância entre os achados da citologia e da histopatologia foi moderada.

The prognostic and predictive value of selected biomarkers in colorectal cancer

Tissue-based biomarkers are studied to receive information about the pathologic processes and cancer outcome, and to enable development of patient-tailored treatments. The aim of this study was to investigate the potential prognostic and/or predictive value of selected biomarkers in colorectal cancer (CRC). Group IIA secretory phospholipase A2 (IIA PLA2) expression was assessed in 114 samples presenting different phases of human colorectal carcinogenesis. Securin, Ki-67, CD44 variant 6 (CD44v6), aldehyde dehydrogenase 1 (ALDH1) and β-catenin were studied in a material including 227 rectal carcinoma patients treated with short-course preoperative radiotherapy (RT), long-course preoperative (chemo)RT (CRT) or surgery only. Epidermal growth factor receptor (EGFR) gene copy number (GCN), its heterogeneity in CRC tissue, and association with response to EGFR-targeted antibodies cetuximab and panitumumab were analyzed in a cohort of 76 metastatic CRC. IIA PLA2 expression was decreased in invasive carcinomas compared to adenomas, but did not relate to patient survival. High securin expression after long-course (C)RT and high ALDH1 expression in node-negative rectal cancer were independent adverse prognostic factors, ALDH1 specifically in patients treated with adjuvant chemotherapy. The lack of membranous CD44v6 in the rectal cancer invasive front associated with infiltrative growth pattern and the risk of disease recurrence. Heterogeneous EGFR GCN increase predicted benefit from EGFR-targeted antibodies, also in the chemorefractory patient population. In summary, high securin and ALDH1 protein expression independently relate to poor outcome in subgroups of rectal cancer patients, potentially because of resistance to conventional chemotherapeutics. Heterogeneous increase in EGFR GCN was validated to be a promising predictive factor in the treatment of metastatic CRC.

TP53 mutations and loss of heterozygosity of chromosome 17 in colorectal tumors

The incidence of TP53 point mutations and loss of heterozygosity (LOH) of chromosome 17 in colorectal tumors was determined in a group of Brazilian patients. We screened DNA samples from tumors and distal normal mucosa of 39 patients with colorectal cancer, for TP53 mutations by PCR-SSCP (single-strand conformation polymorphism) analysis. Chromosome 17 LOH was investigated using six PCR-based polymorphic markers and one VNTR probe. TP53 mutations were demonstrated in 15/39 of the cases. Mutations were distributed among all exons examined (five to eight), the majority of them being G/C to A/T transitions. LOH of chromosome 17p and 17q was detected in 70 and 46% of the tumors, respectively. There was a significant association between TP53 mutations and LOH in chromosome 17p (P = 0.0035) and 17q (P = 0.03). Although no correlation was observed between TP53 genetic alterations and clinical/ pathological characteristics, the association of TP53 mutations with loss of both chromosome 17 arms may indicate that TP53 inactivation provokes an unstable phenotype in tumor cells in colorectal tumors.

Utilization of microsatellites for the analysis of genomic alterations in colorectal cancers in Brazil

Two different pathogenetic mechanisms are proposed for colorectal cancers. One, the so-called "classic pathway", is the most common and depends on multiple additive mutational events (germline and/or somatic) in tumor suppressor genes and oncogenes, frequently involving chromosomal deletions in key genomic regions. Methodologically this pathway is recognizable by the phenomenon of loss of heterozygosity. On the other hand, the "mutator pathway" depends on early mutational loss of the mismatch repair system (germline and/or somatic) leading to accelerated accumulation of gene mutations in critical target genes and progression to malignancy. Methodologically this second pathway is recognizable by the phenomenon of microsatellite instability. The distinction between these pathways seems to be more than academic since there is evidence that the tumors emerging from the mutator pathway have a better prognosis. We report here a very simple methodology based on a set of tri-, tetra- and pentanucleotide repeat microsatellites allowing the simultaneous study of microsatellite instability and loss of heterozygosity which could allocate 70% of the colorectal tumors to the classic or the mutator pathway. The ease of execution of the methodology makes it suitable for routine clinical typing

Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer

Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO), an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control), as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells), alpha3 (93.3 ± 7.0%), alpha5 (50.4 ± 12.0%) and alpha6 (34.1 ± 4.9%) integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0%) and fibronectin (40.0 ± 2.0%) substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5%) while simultaneously reducing alpha5 (24.2 ± 19%) and alpha6 (14.3 ± 10.8%) expression as well as c-myc mRNA (7-fold), the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells), was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression

Curcumin, a major yellow pigment and active component of turmeric, has multiple anti-cancer properties. However, its molecular targets and mechanisms of action on human colon adenocarcinoma cells are unknown. In the present study, we examined the effects of curcumin on the proliferation of human colon adenocarcinoma HT-29 cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method and confirmed the curcumin-induced apoptosis by morphology and DNA ladder formation. At the same time, p53, phospho-p53 (Ser15), and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, pro-caspase-3, and pro-caspase-9 were determined by Western blot analysis. The colon adenocarcinoma cells were treated with curcumin (0-75 µM) for 0-24 h. We observed that p53 was highly expressed in HT-29 cells and curcumin could up-regulate the serine phosphorylation of p53 in a time- and concentration-dependent manner. An increase in expression of the pro-apoptotic factor Bax and a decrease in expression of the anti-apoptotic factor Bcl-2 were also observed in a time-dependent manner after exposure of 50 µM curcumin, while the expression of the anti-apoptotic factor Bcl-xL was unchanged. Curcumin could also down-regulate the expression of pro-caspase-3 and pro-caspase-9 in a time-dependent manner. These data suggest a possible underlying molecular mechanism whereby curcumin could induce the apoptosis signaling pathway in human HT-29 colon adenocarcinoma cells by p53 activation and by the regulation of apoptosis-related proteins. This property of curcumin suggests that it could have a possible therapeutic potential in colon adenocarcinoma patients.