IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER.

BACKGROUND: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. AIM: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. METHODS: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. RESULTS: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). CONCLUSION: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters.

PURPOSE: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. METHODS: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. RESULTS: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP - 2 (p= 0.01 and - 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). CONCLUSIONS: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

Comparison between anal cytology, high-resolution anoscopy and HPV DNA genotyping by polymerase chain reaction in the post-treatment follow-up of condylomata acuminata.

AIM: to evaluate the presence of subclinical HPV-induced anal lesions with anal cytology, High-Resolution Anoscopy (HRA) and HPV genotyping by polymerase chain reaction (PCR) in the follow-up of treated condylomata acuminata (CA). METHODS: seventy-nine male patients were included. One month after anal CA eradication, the patients underwent brush samples collection for anal cytology and PCR, and HRA with biopsy of acetowhite lesions. These methods were compared within all patients and between groups, according to Human Immunodeficiency Virus (HIV) infection status: HIV-negative; HIV-positive with TCD4 count above and below 350 cells/mm3. RESULTS: the most frequent HPV types were 6 and 16. HPV DNA was isolated in 92%. HIV infection was associated with a higher number of oncogenic HPV types (p=0.038). All patients with negative PCR had negative HRA and cytology. There were no differences in cytological, HRA or histopathological findings between groups. CONCLUSION: the association of the findings of cytopathology, HRA and genotyping of HPV refined the diagnosis of HPV-induced lesions. The degree of immunodeficiency was not associated with increase in remnant HPV-induced anal lesions.

Comparison between anal cytology, high-resolution anoscopy and HPV DNA genotyping by polymerase chain reaction in the post-treatment follow-up of condylomata acuminata / Comparação entre citologia anal, colposcopia anal e genotipagem do HPV por reação em cadeia da polimerase no seguimento pós-operatório de condiloma acuminado

ABSTRACT Aim: to evaluate the presence of subclinical HPV-induced anal lesions with anal cytology, High-Resolution Anoscopy (HRA) and HPV genotyping by polymerase chain reaction (PCR) in the follow-up of treated condylomata acuminata (CA). Methods: seventy-nine male patients were included. One month after anal CA eradication, the patients underwent brush samples collection for anal cytology and PCR, and HRA with biopsy of acetowhite lesions. These methods were compared within all patients and between groups, according to Human Immunodeficiency Virus (HIV) infection status: HIV-negative; HIV-positive with TCD4 count above and below 350 cells/mm3. Results: the most frequent HPV types were 6 and 16. HPV DNA was isolated in 92%. HIV infection was associated with a higher number of oncogenic HPV types (p=0.038). All patients with negative PCR had negative HRA and cytology. There were no differences in cytological, HRA or histopathological findings between groups. Conclusion: the association of the findings of cytopathology, HRA and genotyping of HPV refined the diagnosis of HPV-induced lesions. The degree of immunodeficiency was not associated with increase in remnant HPV-induced anal lesions.

RESUMO Objetivo: avaliar a presença de lesões anais subclínicas HPV-induzidas com citologia anal, colposcopia anal e genotipagem de HPV por reação em cadeia da polimerase (PCR) no seguimento de condilomas anais tratados. Método: foram incluídos 79 pacientes do sexo masculino. Após um mês da erradicação de lesões condilomatosas anais, os participantes voltaram em consulta para coleta de amostras com escova para citologia anal e PCR, e colposcopia anal com biópsia de lesões acetobrancas. Os métodos de detecção das lesões foram comparados entre os pacientes e entre grupos, de acordo com o status de infecção pelo vírus da imunodeficiência humana (HIV): HIV-negativo; HIV-positivo com TCD4 acima ou abaixo de 350 células/mm3. Resultados: os tipos de HPV mais frequentes foram 6 e 16. Infecção pelo HIV foi associada a maior número de tipos de HPV oncogênicos (p=0,038). Todos os pacientes com PCR negativo apresentaram colposcopia e citologia negativos. Não houve diferença nos achados citológico, colposcópico ou histopatológico entre grupos. Conclusão: a associação dos achados citopatológico, colposcópico e PCR melhorou a acurácia do diagnóstico de lesões anais HPV-induzidas. O grau de imunodeficiência não foi associado a maior frequência de lesões anais HPV-induzidas remanescentes.

Impact of kras mutations in clinical features in colorectal cancer / Impacto das mutações kras e características clínicas em câncer colorretal

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

RESUMO Racional: Mutações KRAS são eventos importantes na carcinogênese colorretal como preditores negativos de resposta ao tratamento. Objetivo: Investigar a associação de características clinicopatológicas com mutações no KRAS em pacientes com câncer colorretal tratados. Métodos: Sessenta e nove pacientes com câncer colorretal metastáticos ao diagnóstico ou posteriormente foram analisados. As técnicas de sequenciamento direto e pirosequenciamento foram relacionadas ao éxon 2 do KRAS e o diagnóstico da mutação e seu tipo foram determinados. Resultados: A mutação KRAS foi identificada em 43,4% dos pacientes, c.35G>T (p.G12V), c.35G>A (p.G12D) e c.38G>A (p.G13D). Não foi encontrada correlação entre a mutação KRAS e a idade (p=0,646) ou o gênero (p=0,815). No entanto, o grupo mutado apresentou níveis mais altos de CEA na admissão (p=0,048). A mutação do códon 13 foi associada ao envolvimento de mais de um local metastático na progressão da doença (p=0,029); não houve associação entre o local primário do tumor e o diagnóstico de mutação (p=0,568); a doença primária do cólon foi associada com pior sobrevida global (p=0,009). Conclusão: A mutação KRAS foi identificada em quase metade dos pacientes. O grupo KRAS mutado apresentou níveis mais altos de CEA na admissão e a mutação no códon 13 foi associada ao envolvimento de mais de um local metastático no curso da doença. A doença do cólon foi associada com pior sobrevida global.

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters

Abstract Purpose: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. Methods: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. Results: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP - 2 (p= 0.01 and - 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). Conclusions: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

Fecal Genetic Mutations and Human DNA in Colorectal Cancer and Polyps Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent cancers. Genetic mutations in CRC already described can be detected in feces. Microarray methods in feces can represent a new diagnostic tool for CRC and significant improvement at public health. AIM: to analyze stool DNA by human DNA quantify and microarray methods as alternatives to CRC screening. METHOD: Three methods were analyzed in stool samples: Human DNA Quantify, RanplexCRC and KRAS/BRAF/PIK3CA (KBP) Arrays. RESULTS: KBP array mutations were presented in 60.7% of CRC patients and RanplexCRC Array mutations in 61.1% of CRC patients. Sensitivity and specificity for human DNA quantification was 66% and 82% respectively. Fecal KBP Array had 35% sensitivity and 96% specificity and RanplexCRC Array method had 78% sensitivity and 100% specificity. CONCLUSION: Microarray methods showed promise as potential biomarkers for CRC screening; however, these methods had to be optimized to improve accuracy and applicability by clinical routine.

Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer.

BACKGROUND: The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. The objective of the study was to verify the variables involved in the nutritional status and genetic mutations, which correlate with survival of CRC patients. METHODS: Patients with surgical intervention for tumor resection were evaluated using body mass index, nutritional screening, patient self-produced global subjective assessment, phase angle, and computed tomography to calculate the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue, and muscle mass for the determination of sarcopenia. Ten gene mutations involved in CRC carcinogenesis were studied (PIK3CA, KRAS, BRAF, EGFR, NRAS, TP53, APC, PTEN, SMAD4, and FBXW7). DNA was extracted from fresh tumor or paraffin tissues. RESULTS: Of the 46 patients, 29 (64.4%) were at nutritional risk and 21 (45.7%) were moderately malnourished. However, there was a high percentage of VAT in 24 (61.5%) and sarcopenia in 19 (48.7%) patients. These variables were associated with a higher risk of mortality. Nutritional risk, moderate or severe malnutrition, phase angle < 5°, VAT < 163.8 cm2 in men and <  80.1 cm2 in women, and sarcopenia were associated with the relative risk of death, with respective hazard ratios/odds ratios and 95% confidence intervals of 8.77 (1.14-67.1), 3.95 (1.11-14.0), 3.79 (1.10-13.1), 3.43 (1.03-11.4), and 3.95 (1.06-14.6). Increased VAT was associated with a lower risk of death, even in patients older than 60 years or those harboring mutated KRAS. CONCLUSIONS: Patients with positive indicators for malnutrition or risk of malnutrition had an increased risk of death. No relationship was identified between the presence of mutations and survival.

Heparan Sulfate Proteoglycans in Human Colorectal Cancer.

Colorectal cancer is the third most common cancer worldwide, accounting for more than 610,000 mortalities every year. Prognosis of patients is highly dependent on the disease stage at diagnosis. Therefore, it is crucial to investigate molecules involved in colorectal cancer tumorigenesis, with possible use as tumor markers. Heparan sulfate proteoglycans are complex molecules present in the cell membrane and extracellular matrix, which play vital roles in cell adhesion, migration, proliferation, and signaling pathways. In colorectal cancer, the cell surface proteoglycan syndecan-2 is upregulated and increases cell migration. Moreover, expression of syndecan-1 and syndecan-4, generally antitumor molecules, is reduced. Levels of glypicans and perlecan are also altered in colorectal cancer; however, their role in tumor progression is not fully understood. In addition, studies have reported increased heparan sulfate remodeling enzymes, as the endosulfatases. Therefore, heparan sulfate proteoglycans are candidate molecules to clarify colorectal cancer tumorigenesis, as well as important targets to therapy and diagnosis.

Argon plasma versus electrofulguration in the treatment of anal and perianal condylomata acuminata in patients with acquired immunodeficiency virus.

PURPOSE:: To compare the effectiveness of anal and perianal condylomata treatment using argon plasma and electrofulguration. METHODS:: From January 2013 to April 2014, 37 patients with anal and perianal condylomata, who had been diagnosed through proctological examination, oncotic cytology, polymerase chain reaction (PCR) and histology, underwent treatment with argon plasma and electrofulguration. The perianal and anal regions were divided into two semicircles. Each semicircle was treated using one of the methods by means of simple randomization. Therapeutic sessions were repeated until all clinical signs of infection by HPV were eliminated. The patients were evaluated according to several variables like the genotype of HPV, HIV infection, oncological potential per genotype, oncotic cytology and histology. RESULTS:: Among all the variables studied, only immunosuppression due to HIV influenced the results, specifically when the fulguration method was used. There was no significant difference in effectiveness between argon and fulguration based on lesion relapse (p > 0.05). However, among HIV-positive patients, fulguration presented worse results, with a significant difference (p = 0.01). CONCLUSION:: Regarding treatment of anal and perianal condylomata acuminata, comparison between applying fulguration and argon demonstrated that these methods were equivalent, but use of fulguration presented more relapses among HIV-positive patients.

Argon plasma versus electrofulguration in the treatment of anal and perianal condylomata acuminata in patients with acquired immunodeficiency virus

Abstract Purpose: To compare the effectiveness of anal and perianal condylomata treatment using argon plasma and electrofulguration. Methods: From January 2013 to April 2014, 37 patients with anal and perianal condylomata, who had been diagnosed through proctological examination, oncotic cytology, polymerase chain reaction (PCR) and histology, underwent treatment with argon plasma and electrofulguration. The perianal and anal regions were divided into two semicircles. Each semicircle was treated using one of the methods by means of simple randomization. Therapeutic sessions were repeated until all clinical signs of infection by HPV were eliminated. The patients were evaluated according to several variables like the genotype of HPV, HIV infection, oncological potential per genotype, oncotic cytology and histology. Results: Among all the variables studied, only immunosuppression due to HIV influenced the results, specifically when the fulguration method was used. There was no significant difference in effectiveness between argon and fulguration based on lesion relapse (p > 0.05). However, among HIV-positive patients, fulguration presented worse results, with a significant difference (p = 0.01). Conclusion: Regarding treatment of anal and perianal condylomata acuminata, comparison between applying fulguration and argon demonstrated that these methods were equivalent, but use of fulguration presented more relapses among HIV-positive patients.

Flebotônicos para hemorroida / Hemorrhoid phlebotonic

Introdução: As hemorroidas são dilatações de varizes do plexo venoso anal e perianal e frequentemente são secundárias à pressão venosa persistentemente elevada dentro do plexo hemorroidário. Os flebotônicos são uma classe heterogênea de medicamentos contendo extratos de plantas (por exemplo, flavonoides) e compostos sintéticos (por exemplo, dobesilato de cálcio). Embora seu mecanismo de ação exato ainda não tenha sido completamente estabelecido, eles parecem melhorar o tônus venoso, estabilizar a permeabilidade capilar e aumentar a drenagem linfática. Os flebotônicos têm sido utilizados para tratar uma variedade de condições, incluindo a insuficiência venosa crônica, linfedema e hemorroidas.Objetivo: Avaliar a eficácia dos flebotônicos em aliviar os sinais, sintomas e melhorar a gravidade da doença hemorroidária e verificar seu efeito pós-hemorroidectomia.Métodos:Métodos de busca: Foi realizada busca nas bases Central (The Cochrane Library 2011, Edição 9), Medline (1950 a setembro de 2011) e Embase (1974 a setembro de 2011).Critérios de seleção: Foram incluídos apenas ensaios clínicos randomizados avaliando o uso de flebotônicos no tratamento da doença hemorroidária. Estudos quasi-randomizados, crossover ou cluster foram excluídos.Coleta e análise de dados: Dois autores extraíram independentemente os dados e analisaram a elegibilidade dos dados para inclusão. Discordâncias foram resolvidas por discussão. Principais resultados: Foram considerados 24 estudos para a inclusão na análise final. Vinte destes estudos (incluindo um total de 2.344 participantes) avaliaram o uso de flebotônicos versus uma intervenção de controle. Um desses vinte estudos avaliou o uso de flebotônicos com uma intervenção clínica e um outro estudo com ligadura elástica.Conclusões dos autores: As evidências sugerem que há uma vantagem potencial na utilização da flebotônicos no tratamento da doença hemorroidária, bem como benefício no alívio dos sintomas pós-hemorroidectomia. Desfechos como hemorragia e melhora global dos sintomas mostraram um efeito benéfico estatisticamente significativo e houve poucas preocupações em relação à sua segurança global.

Preferência do paciente no rastreamento do câncer colorretal: uma comparação entre colonografia por tomografia computadorizada e colonoscopia / Patient preferences toward colon cancer screening: a comparison between computed tomography colonography and conventional colonoscopy

OBJETIVO: Avaliar o grau de aceitação do paciente submetido a colonografia por tomografia computadorizada (CTC) em comparação com a colonoscopia, quando realizadas para rastreamento de doença colorretal. MATERIAIS E MÉTODOS: Cinquenta pacientes com suspeita de doença colorretal foram submetidos a CTC e colonoscopia. Questionários foram aplicados antes e após a realização da CTC e após a colonoscopia. Graduou-se o desconforto esperado e experimentado antes e após a realização da CTC e da colonoscopia, bem como a preferência do paciente por exame. RESULTADOS: Em relação à CTC, antes de iniciar o exame 18 por cento dos pacientes afirmaram esperar pouco desconforto, 78 por cento, desconforto moderado e 4 por cento, muito desconforto. Após a realização do exame, 72 por cento dos pacientes relataram pouco desconforto, 26 por cento, desconforto moderado e apenas um (2 por cento) dos pacientes referiu muito desconforto. Após a realização da colonoscopia, 86 por cento dos pacientes relataram preferência pela CTC. O grau de distensão colônica e a quantidade de fluido residual não influenciaram na preferência dos pacientes. CONCLUSÃO: Os pacientes preferiram a CTC à colonoscopia, não havendo relação estatística com o grau de distensão colônica na CTC e a eficiência do preparo intestinal.

OBJECTIVE: To assess the degree of acceptance of patients undergoing computed tomography colonography (CTC) in comparison with colonoscopy in the screening of colorectal disease. MATERIALS AND METHODS: Fifty patients with suspected colorectal disease underwent CTC and colonoscopy. Questionnaires were administered before and after the performance of the CTC and after the colonoscopy. The discomfort expected and experienced before and after the performance of both procedures as well as the patients' preference for each method were evaluated. RESULTS: As regards CTC, before the procedure, 18 percent of the patients reported expecting little discomfort, 78 percent, mild discomfort, and 4 percent, a lot of discomfort. After the procedure, 72 percent of the patients reported little discomfort, 26 percent, mild discomfort, and only one (2 percent) of the patients reported a lot of discomfort. Upon completion of the colonoscopy, 86 percent of the patients reported their preference for CTC. The degree of colonic distention and residual amount of fluid had no influence on the patients' preference. CONCLUSION: CTC was preferred to colonoscopy, with no statistical relationship with the degree of colonic distention at CTC and efficiency of bowel preparation.

Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs).

Monocarboxylate transporters (MCTs) have been described to play an important role in cancer, but to date there are no reports on the significance of MCT expression in gastrointestinal stromal tumors (GISTs). The aim of the present work was to assess the value of MCT expression, as well as co-expression with the MCT chaperone CD147 in GISTs and evaluate their clinical-pathological significance. We analyzed the immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 in a series of 64 GISTs molecularly characterized for KIT, PDGFRA and BRAF mutations. MCT1, MCT2 and MCT4 were highly expressed in GISTs. CD147 expression was associated with mutated KIT (p = 0.039), as well as a progressive increase in Fletcher's Risk of Malignancy (p = 0.020). Importantly, co-expression of MCT1 with CD147 was associated with low patient's overall survival (p = 0.037). These findings suggest that co-expression of MCT1 with its chaperone CD147 is involved in GISTs aggressiveness, pointing to a contribution of cancer cell metabolic adaptations in GIST development and/or progression.

Lymphangiogenic VEGF-C and VEGFR-3 expression in genetically characterised gastrointestinal stromal tumours.

This study aimed to assess the distribution of VEGF-C and VEGFR-3 expression in gastrointestinal stromal tumours (GISTs), and to analyse the value of lymphatic vessel density (LVD) in a tumour that is believed to preferentially metastasize through blood vessel conduits. A panel of immunohistochemical antibodies was used to evaluate 51 cases of genetically characterised GISTs: VEGF-C, VEGFR-3, D2-40 (for LVD assessment) and CD31 (for blood vessel density--BDV--assessment). The results were correlated with the clinical-pathological data. The large majority of cases (86.2%; 44/51) showed a mutation of the KIT gene, most of them (72.5%; 37/51) revealing mutations in exon 11. VEGFR-3 was predominantly expressed in KIT mutated GISTs (p=0.019). High LVD was correlated with the absence of metastasis (p=0.010) and high BVD showed a positive correlation with the occurrence of metastasis (p=0.049). The strong expression of VEGF-C and VEGFR-3 in GIST's cells was not correlated with the clinical parameters of aggressiveness, nor with high LVD.

Study of APC and betha-catenin protein expression in polyps and colorectal adenocarcinoma

OBJECTIVE: To study part of the Wnt signaling pathway for carcinogenesis in colorectal cancer and polyps, through adenomatous polyposis coli (APC) and β-catenin protein expression. METHODS: We studied the immunoexpression of APC protein and β-catenin in the adenocarcinoma and polyps (adenoma) from ninety-one patients who underwent resection of sporadic colorectal cancer (CRC) with curative intent from 1993 to 2004 at the Hospital do Câncer de Barretos (Brazil). Each patient was resected within a period 3 months before or after diagnosis. The polyps or adenocarcinoma was considered positive for APC when more than 10% of the cells showed cytoplasmic staining and for β-catenin when more than 5% of the cells showed nuclear stainning. RESULTS: Among the 91 patients, we found association among APC protein expression in the polyps and in the respective colorectal adenocarcinoma (p = 0.014). Similarly, there were significant association with nuclear expressions (p = 0.001) of β-catenin in the polyps and colorectal adenocarcinoma. Nuclear β-catenin expression was associated with villous adenoma (86%, p = 0.042). There was no association among APC and β-catenin expression and any other histological finding. CONCLUSION: There is an association of APC and β-catenin protein expression in polyps and in colorectal adenocarcinoma. This finding allows us to speculate that in the same patient the same WNT pathway or another is activated in both lesions; polyp and adenocarcinoma. Villous adenomas occur most frequently via the Wnt signaling pathway.

MET Is highly expressed in advanced stages of colorectal cancer and indicates worse prognosis and mortality.

UNLABELLED: The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients submitted to surgical resection due to primary colorectal adenocarcinoma. PATIENTS AND METHODS: A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware of patient clinical and histopathological data. RESULTS: The tumor marker expression was positive in 236 (79%) out of a total of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and recurrence (p=0.89) or disease-free interval (p=0.91) was observed. CONCLUSION: MET has shown significant expression at advanced stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker for poor prognosis in colorectal cancer patients.

Influência da idade e da doença colorretal na imunocompetência cutânea peri-colostômica / Influence of the age and disease colorectal in immunity cutaneous pericolostomic

Objetivo: Caracterizar a resposta imunológica presente na camada dérmica da região peri-colostômica. Método: Foram incluídos quarenta e um doentes, portadores de colostomias realizadas há mais de oito semanas. Na determinação imuno-histoquímica foram avaliados os linfócitos Pan T, linfócito T - auxiliar, linfócito T - citotóxico, linfócito B, linfócito T - Natural Killer e os macrófagos. Resultados: Na análise da resposta imune-celular, independente da doença colorretal, foi observada uma relação com significância estatística quando se comparou os valores dos linfócitos Pan T, linfócito T - auxiliar, linfócito T - citotóxico e dos macrófagos, com as do linfócito B, linfócito T - Natural Killer. Na análise da resposta imune-celular de acordo com a idade, observou-se uma significância estatística da relação do linfócito Pan T, linfócito T - auxiliar e do macrófago, com as do linfócito B, linfócito T - Natural Killer, em ambas as faixas etárias, além do linfócito T - citotóxico com as do linfócito B, linfócito T - Natural Killer na faixa etária adulta. Conclusão: A presença da colostomia determina o desenvolvimento de uma resposta imune-celular na camada dérmica da região peri-colostômica, sendo composta em maior número pelo linfócito Pan T, linfócito T - auxiliar, linfócito T - citotóxico e macrófagos.

Objective: describe the immunological response in the dermal layer of the peri-colostomic region. Method: Forty-one patients with colostomies realized over eight weeks previously, were included. For the analysis of the immunocellular response in the peri-colostomic dermal region, the values of Pan T lymphocytes, T lymphocytes - helper, T lymphocytes - cytotoxic, lymphocytes B, T lymphocytes - Natural Killer and macrophages. Results: Analysis of the immuno-cellular response showed that both in the benign colorectal disease as well as in the malignant one number of Pan T lymphocytes, T lymphocytes - helper, T lymphocytes - cytotoxic and macrophages were statistically significant relationship major than B Lymphocytes and T lymphocytes - Natural Killer. Analysis of the immuno-cellular response based on age, demonstrated that both the adult age bracket as well as the geriatric one, displayed a major number of Pan T lymphocytes, T lymphocytes - helper and macrophages, with their numerical value significantly than the B lymphocytes and the T lymphocytes - Natural Killer, beyond the T lymphocytes - cytotoxic with the B lymphocytes and the T lymphocytes - Natural Killer in the adult age. Conclusion: The presence of a colostomy promotes the development of an immuno-cellular response in the dermal layer of the peri-colostomy region that is composed of a major number of Pan T lymphocytes, T lymphocytes - helper, T lymphocytes - cytotoxic and macrophages.

Acidose metabólica por hiperglicemia transitória pós enucleação de insulinoma pancreático / Metabolic acidosis secondary to transient hyperglycemia after pancreatic insulinoma enucleation

INTRODUÇÃO: Insulinoma é a neoplasia endócrina mais frequente dos tumores funcionantes do pâncreas. Origina-se a partir das células beta das ilhotas de Langerhans e caracteriza-se pela produção excessiva de insulina, com consequente hipoglicemia. O tratamento de escolha é a remoção cirúrgica da neoplasia. O presente relato tem como objetivo apresentar uma complicação metabólica pouco observada.RELATO DO CASO: Homem de 41 anos de idade há dois anos com tonturas, visão turva e convulsões. Os sintomas estavam bem relacionados com períodos prolongados de jejum e melhoravam com as refeições, e durante um dos episódios foi constatada a presença de hipoglicemia, melhorando os sintomas imediatamente após administração de glicose endovenosa. A pesquisa glicêmica revelou intensa hipoglicemia. Ultrassonografia, tomografia computadorizada e ressonância magnética de abdome não revelaram nenhum tipo de alterações no pâncreas. Com a hipótese diagnóstica de hiperglicemia orgânica por provável insulinoma, o paciente foi submetido à enucleação da lesão. No 5º dia do pós-operatório surgiu fístula pancreática e acidose metabólica com resolução satisfatória. O laudo histopatológico mostrou tumor endócrino de pâncreas de 1,5 cm.CONCLUSÃO: Todo paciente submetido à ressecção de insulinoma pancreático deve realizar o pós-operatório imediato em unidades de terapia intensiva, monitorando de forma rigorosa os níveis de glicemia como prevenção de acidose metabólica.

INTRODUCTION: The insulinoma is the most frequent endocrine neoplasm among the functional pancreatic tumors. It originates in the beta cells of the islets of Langerhans and is characterized by the oversecretion of insulin, leading to hypoglycemia. The treatment of choice is the surgical excision of the tumor. The aim of the present report is to describe a rarely observed metabolic complication.CASE REPORT: The case is presented of a 41-year-old man with a 2-year history of dizziness, blurred vision and seizures. The symptoms were closely related to prolonged fasting and improved with eating; hypoglycemia was found during one of the episodes. Symptoms were relieved immediately after intravenous administration of glucose. Blood glucose workup showed severe hypoglycemia. Abdominal ultrasonography, computed tomography and magnetic resonance imaging did not show any alteration in the pancreas. With the diagnostic hypothesis of organic hypoglycemia from a likely insulinoma, the patient underwent the enucleation of the lesion. On the 5th postoperative day, a pancreatic fistula appeared, as well as metabolic acidosis which resolved satisfactorily. The histopathological report showed a 1.5-cm endocrine pancreatic tumor.CONCLUSION: Every patient submitted to pancreatic insulinoma resection should stay in an intensive care unit during the immediate postoperative period and their glycemic levels must be monitored closely to prevent metabolic acidosis.