Quality of life following pelvic exenteration in neoplasms.

BACKGROUND: Pelvic exenteration (PE) is an extensive surgical treatment reserved for advanced or recurrent pelvic neoplasms, with potential impacts on patients' quality of life (QoL) poorly referenced in the literature. OBJECTIVES: This study aimed to evaluate QoL outcomes among three types of PE. METHODS: A cross-sectional study assessed 106 patients divided into anterior PE (APE), posterior PE (PPE), or total PE (TPE) groups. QoL was measured using e short form 36 version 2 (SF-36) and the European Organization for Research and Treatment of Cancer QoL Quality of Life Questionnaire Core 30 (QLQ-C30) QoL questionnaires. Descriptive and inferential analyses compared questionnaire scores. RESULTS: The findings unveiled a balance among the three groups concerning demographic variables and comorbidities, with the exception of a male predominance in the APE and TPE cohorts. Notably, the APE group exhibited elevated scores in overall health (assessed via SF-36) and social functioning and diarrhea domains (assessed via QLQ-C30). Moreover, in terms of the fatigue and nausea/vomiting domains (assessed via QLQ-C30), the APE group demonstrated superior QoL compared to the PPE group. Conversely, the PPE group manifested a notably lower QoL in the constipation domain (assessed via QLQ-C30) compared to the other two groups. Additionally, disease recurrence was significantly associated with diminished QoL across multiple domains. CONCLUSION: APE patients exhibited better QoL than PPE and TPE groups, with disease recurrence adversely affecting QoL.

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.

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.

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.

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.

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.

Understanding the Effects of Colostomy-induced Alterations on Cutaneous Immunity .

UNLABELLED:  Objective. This study describes the immunological response in the dermal layer of the peri-colostomic region, and identifies and quantifies the cellular elements present. METHODS: Forty-one patients with colostomies present for more than 8 weeks were included. Thirty-one patients were men (75.6%) and 10 were women (24.4%) with an average age of 49.9 years. Thirty-four patients (82.9%) were classified as surgical risk class I and 7 patients (17.1%) were classified as class II. The data were analyzed statistically using the Mann-Whitney, Kruskal-Wallis, and Dunn tests using 0.05 or 5%. RESULTS: Analysis of the immuno-cellular response regarding the time of permanence of the colostomy showed a significant frequency of T lymphocytes (pan T-CD3) in all the time periods in a significantly superior number (P < 0.001) than the B lymphocytes (CD20) and the T lymphocytes-natural killer (CD57). T-helper cells (CD4) were present in larger numbers in the first three periods. CONCLUSION: The presence of a colostomy for more than 8 weeks promotes the development of a chronic inflammation and an immuno-cellular response in the dermal layer of the peri-colostomy region. However, its intensity did not demonstrate a statistically significant difference based on time of colostomy existence. The immuno-cellular response in the peri-colostomic dermal area is composed of a major number of T lymphocytes (pan T-CD3) and T lymphocytes-helper (CD4), and is more numerous between the 16th and 20th weeks, whereas, less cellular activity was noted between the 30th and 50th weeks. .

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.

Rubber band ligation and infrared photocoagulation for the outpatient treatment of hemorrhoidal disease.

PURPOSE: To compare the results of rubber band ligation and infrared photocoagulation for the treatment of hemorrhoidal disease through the analysis of the incidence of complications after each treatment and respective success rate. METHODS: Forty-eight patients with first, second or third degree hemorrhoidal disease were randomized to receive treatment with either rubber band ligation (n=23) or infrared photocoagulation (n=25). Each patient was assessed at 1 week and 4 week intervals after treatment. We compared the incidence of complications and efficiency of each treatment modality and Qui-square, Fisher's Exact Test and Student's t Test were used to statistical analysis. RESULTS: Bleeding occured in eight (34,7%) patients treated with rubber band ligation and in four (16,0%) after infrared photocoagulation (p=0,243). Thirteen (52,0%) patients felt pain during infrared photocoagulation and 9 (39,1%) after rubber band ligation (p=0,546). After rubber band ligation, 14 (60,8%) required medication for pain relief. One patient (4,0%) required medication after infrared photocoagulation (p<0,001). Three (13,0%) patients treated with rubber band ligator and 1 (4,0%) treated with infrared photocoagulation had symptomatic mucosal ulcers. Perianal dermatitis occured in two (8,0%) patients treated with infrared photocoagulation and one patient (4,3%) was observed to have prolapsed thrombosed piles after rubber band ligation. One month after treatment, 17 of 23 patients treated with rubber band ligation (73,9%) and 18 of 25 patients treated with infrared photocoagulation were asymptomatic. Rubber band ligation treated bleeding and prolapse in 90,0% and 82,4% respectively. Infrared photocoagulation treats bleeding and prolapse in 93,7% and 87,5% respectively. Those differences are not significant. CONCLUSION: Rubber band ligation causes significantly more pain than infrared photocoagulation during the first week after the procedures and their success rate are not different after four weeks of treatment.

Ileostomy or colostomy for temporary decompression of colorectal anastomosis. Systematic review and meta-analysis.

PURPOSE: The controversy regarding whether loop ileostomy or loop transverse colostomy is a better method for temporary decompression of colorectal anastomosis motivated this review. METHODS: Five randomized trials were included, with 334 patients: 168 in the loop ileostomy group and 166 in the loop transverse colostomy group. The outcomes analyzed were: 1. Mortality; 2. Wound infection; 3. Time of stoma formation; 4. Time of stoma closure; 5. Time interval between stoma formation and closure; 6. Stoma prolapse; 7. Stoma retraction; 8. Parastomal hernia; 9. Parastomal fistula; 10. Stenosis; 11. Necrosis; 12. Skin irritation; 13. Ileus; 14. Bowel leakage; 15. Reoperation; 16. Patient adaptation; 17. Length of hospital stay; 18. Colorectal anastomotic dehiscence; 19. Incisional hernia; 20. Postoperative bowel obstruction. RESULTS: Stoma prolapse was statistically significant (p = 0.00001), but with statistical heterogeneity; the sensitive analysis was applied, excluding the trials that included emergency surgery, and this showed: p = 0.02, with I2 = 0% for the heterogeneity test. CONCLUSIONS: The outcomes reported were not statistically or clinically significant except for stoma prolapse. Better evidence for making the choice between loop ileostomy or loop colostomy requires large-scale randomized controlled trials.

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.

Analysis of bacteremia occurring in the presence of obstruction of the left colon in rats submitted to transoperative antegrade mechanical lavage.

With the objective of determining the association between bacteremia and transoperative antegrade mechanical lavage of the colon in an experimental model of obstruction of the left colon in rats, 40 male Wistar rats aged between 90 and 120 days were divided randomly into four groups: A, with intestinal obstruction and with mechanical lavage of the colon; B, with intestinal obstruction and without mechanical lavage of the colon; C, without intestinal obstruction and with mechanical lavage of the colon; and D, without intestinal obstruction and without mechanical lavage of the colon. Analysis of the results showed that there was no bacteremia in the animals in the sham group. On the other hand, bacterial growth in blood cultures was found in three animals (30%) in group C and in four animals (40%) in group B. Positive blood culturing was presented by eight animals (80%) of the rats in group A, and variance analysis on this finding was statistically significant (p = .0029). It can be concluded that, in this experimental model, intestinal obstruction causes a fourfold increase in the risk of bacteremia, while lavage causes an almost threefold increase in the chance of bacterial dissemination into the blood stream. This explains why there was greater incidence of bacteremia in the animals with obstruction and with lavage.

Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins.

PURPOSE: To evaluate the prognostic significance and correlation with staging and degree of cell differentiation of the tumoral expression of the proteins c-erbB-2 and E-cadherin, in patients with colorectal adenocarcinoma. METHODS: The study included 117 patients with an average age of 63.1 years and an average follow-up duration of 28.1 months. The disease-free interval, survival, incidence of recurrence and specific mortality were evaluated. c-erbB-2 anti-oncoprotein antibodies (Dako) were utilized via the streptavidin-biotin technique. Samples were considered to be positive for c-erbB-2 if 10% or more of the tumor cell membranes were stained. The anti-E-cadherin antibodies (Dako), evaluated this protein and is considered positive, if 50% or more of the cell membranes were stained. Statistical analysis was performed using Pearson's chi-squared test, Fisher's exact test, Kaplan-Meier's estimator, the log-rank test and Wilcoxon's test (Breslow version), setting the level of statistical significance at 5% (p<0.05). RESULTS: 52 of 108 patients studied for c-erbB-2 were positive (48.1%), 47 of 93 patients studied for E-cadherin were negative (50.5%). These data do not express any correlation with TNM (tumor, node and metastasis) staging and the degree of cell differentiation or with the tumor recurrence rate. The disease-free interval among patients who were positive for c-erbB-2 and negative for E-cadherin was 68.0 months and did not differ from those with c-erbB-2 negative and E-cadherin positive (55.0 months--p = 0.5510). The average survival among patients positive for c-erbB-2 and negative for E-cadherin was 75 months without statistical significance difference with the other group (61 months--p = 0.5256). Specific mortality occurred in 20.0% of the cases and did not correlate with the expression of c-erbB-2 (p=0.446), E-cadherin (p=0.883). CONCLUSION: The tumoral expression of c-erbB-2 and E-cadherin did not demonstrate a correlation with the staging and degree of cell differentiation, and it did not present prognostic value regarding disease recurrence, disease-free interval, survival and specific mortality among patients with colorectal adenocarcinoma.

Analysis of the correlation between p53 and bcl-2 expression with staging and prognosis of the colorectal adenocarcinoma.

PURPOSE: To analyze the correlation between p53 and bcl-2 expression and colorectal adenocarcinoma staging and prognosis. METHODS: This was a retrospective series of 125 colorectal adenocarcinoma patients (67 women and 58 men; ages 30-87 years) who underwent surgery with curative intent. The mean follow-up was 28.5 months (range: 2-96 months). TNM staging, tumor recurrence, survival and cancer-related mortality were analyzed. Immunoreactivity was evaluated using DO7 (Dako) for p53 and K492 (Dako) for bcl-2. Tumors with accumulation of staining for cytoplasmic bcl-2 or nuclear p53 in more than 10% of cells were considered positive. Statistical analysis utilized Pearson chi-squared, log-rank and Wilcoxon tests, and Kaplan-Meier survival estimation (significance level: p<0.05). RESULTS: p53+ was found in 11.8% (14/118), bcl-2+ in 50% (58/116) and associated p53+/bcl-2+ in 6.4% (7/109) of the tumors. There was no significant correlation between expression of these biomarkers and TNM I, II, III and IV staging (p=0.385 for p53; p=0.461 for bcl-2). For tumor recurrence, p53+ was found in 9.5% (2/21), bcl-2+ in 50% (11/22), and associated p53+/bcl-2+ in 5.2% (1/19) of the tumors (p=0.714, p=1.000 and p=0.960, respectively). For survival analysis, p53+: 57 months (45.0-68.0), bcl-2+: 78 (37.0-89.0), and p53+/bcl-2+: 62 (56.0-68.0) (p=0.319). For cancer-related mortality, p53+: 8.3% (3/36), bcl-2+: 47.2% (17/36), and p53+/bcl-2+: 5.9% (2/36) of the patients (p=0.432, p=0.688 and p=0.907, respectively). CONCLUSION: No correlation was found between tumor expression of p53 and bcl-2 and the TNM staging, recurrence, survival and cancer-related mortality 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 / 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.

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.

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.

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.

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.