Improvement in the Neutrophil-Lymphocyte Ratio after Combined Fluorouracil, Leucovorina and Oxaliplatino based (FOLFOX) Chemotherapy for Stage III Colon Cancer is Associated with Improved Minimal Residual Disease and Outcome.

INTRODUCTION: Minimal residual disease (MRD) is the net result of the biological properties of disseminated tumour cells and the effect of the immune system and treatment to eliminate them. The aim of this study was to analyse the effect of combined chemotherapy on the immune function as determined by the neutrophil-lymphocyte ratio (NLR) and if it was associated with changes in the subtype of minimal residual disease and outcome in stage III colon cancer. METHODS AND PATIENTS: A prospective, single centre observational study; the NLR was determined immediately prior to and one, two and three months after completing chemotherapy. Circulating tumour cells (CTCs) and bone marrow micro-metastasis (mM) using immunocytochemistry with anti-CEA were determined prior to and one month after chemotherapy. The association of changes in the NLR with MRD subtypes classified as Group I (negative for CTCs and mM), Group II (positive for mM) and Group III (positive for CTCs) as a result of chemotherapy and five-year disease free progression (DFS) analysed. RESULTS: One hundred and eighty eight patients participated of whom 83 (44.9%) relapsed. In non-relapsing patients the NLR significantly increased and was higher after chemotherapy compared with relapsing patients. Significant increases in the NLR were associated with changes to a better MRD prognostic subtype and decreases with a worse MRD subtype. Neither baseline NLR nor MRD subtype predicted response to chemotherapy. DFS for MRD subgroups were 88%, 56% and 6% for Groups I to III respectively. CONCLUSIONS: Immune function as measured by the NLR is associated with MRD prognostic subtypes, improvements in the NLR are associated with improvements in MRD post chemotherapy but neither baseline NLR or MRD predicted outcome.

Different variables predict the outcome of patients with synchronous versus metachronous metastases of colorectal cancer.

PURPOSE: Timing of metastasis is a controversial prognostic factor for patients with metastatic colorectal cancer (mCRC), as well as the performance of the common prognostic variables within patients with synchronous (SMs) or metachronous metastases (MMs). The aim of the current study is to evaluate outcome by the timing of metastases and to explore different tumor characteristics associated with SMs and MMs. METHODS: Data were collected from the clinical records of patients with mCRC, which were referred to the Department of Oncology of the Ospedale Civile di Sanremo from 2006 to 2011. A comparison of the characteristics of tumors of patients, overall and by the timing of metastases, and a Cox regression analysis have been performed to select the most relevant prognostic factors. Finally, the characteristics of the variables associated with the outcome were analyzed through a logistic regression. RESULTS: Two hundreds fifteen patients with SMs and two hundreds ten with MMs were included. Patients with SMs reported a poor prognosis (18.5 versus 62.8 months; p value < 0.001). Among patients with SMs there was a significant difference in overall survival between patients with a CEA-positive or negative disease, while no difference was present among patients with MMs. After multivariate analysis, only within the SMs group the occurrence of liver metastases was related to a CEA-positive disease. CONCLUSIONS: Within the cohort of SMs high CEA levels, occurrence of liver metastases and right-sided colon tumors were associated with a very poor prognosis, whereas no relationship was detectable in the group of patients with MMs.

Prognostic value of thrombocytosis in patients undergoing surgery for colorectal cancer with synchronous liver metastases.

PURPOSE: The purpose of this study was to evaluate the prognostic role of thrombocytosis in patients with synchronous colorectal liver metastases (CRLM). METHODS: Retrospective analysis of patients who underwent surgery for colorectal cancer with synchronous CRLM at the Division of General and Hepatobiliary Surgery, University of Verona Hospital Trust between 2005 and 2016. RESULTS: One hundred and ninety-six patients met the inclusion criteria. High platelet count (H-PC) was found in 32%, and it was associated with a higher rate of palliative surgery (p < 0.001), extra-hepatic metastases (p < 0.001), bilobar liver disease (p = 0.007), presence of more than three metastases (p = 0.005), biggest metastasis larger than 5 cm (p < 0.001), and CEA level higher than 200 ng/mL (p = 0.035). H-PC was significantly associated with poorer 5-year overall survival (14.3% vs. 34.3%; p = 0.001). At the multivariate analysis on R0-1 cases, platelet count resulted the only independent predictor of survival (HR 2.07, p = 0.036). CONCLUSION: H-PC correlates with the main negative clinical-pathological factors in patients with synchronous CRLM, as well as with overall survival. Moreover, it was the only independent prognostic factor in those who underwent curative surgery.

Microbiota modification by probiotic supplementation reduces colitis associated colon cancer in mice.

AIM: To investigate the effect of probiotic supplementation during the development of an experimental model of colitis associated colon cancer (CAC). METHODS: C57BL/6 mice received an intraperitoneal injection of azoxymethane (10 mg/kg), followed by three cycles of sodium dextran sulphate diluted in water (5% w/v). Probiotic group received daily a mixture of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum. Microbiota composition was assessed by 16S rRNA Illumina HiSeq sequencing. Colon samples were collected for histological analysis. Tumor cytokines was assessed by Real Time-PCR (Polymerase Chain Reaction); and serum cytokines by Multiplex assay. All tests were two-sided. The level of significance was set at P < 0.05. Graphs were generated and statistical analysis performed using the software GraphPad Prism 5.0. The project was approved by the institutional review board committee. RESULTS: At day 60 after azoxymethane injection, the mean number of tumours in the probiotic group was 40% lower than that in the control group, and the probiotic group exhibited tumours of smaller size (< 2 mm) (P < 0.05). There was no difference in richness and diversity between groups. However, there was a significant difference in beta diversity in the multidimensional scaling analysis. The abundance of the genera Lactobacillus, Bifidobacterium, Allobaculum, Clostridium XI and Clostridium XVIII increased in the probiotic group (P < 0.05). The microbial change was accompanied by reduced colitis, demonstrated by a 46% reduction in the colon inflammatory index; reduced expression of the serum chemokines RANTES and Eotaxin; decreased p-IKK and TNF-α and increased IL-10 expression in the colon. CONCLUSION: Our results suggest a potential chemopreventive effect of probiotic on CAC. Probiotic supplementation changes microbiota structure and regulates the inflammatory response, reducing colitis and preventing CAC.

Analysis of specific serum markers of colon carcinoma using a Bhattacharyya-based support vector machine.

We aimed to evaluate the specificity of 12 tumor markers related to colon carcinoma and identify the most sensitive index. Bhattacharyya distance was used to evaluate the index. Then, different index combinations were used to establish a support vector machine (SVM) diagnosis model of malignant colon carcinoma. The accuracy of the model was checked. High accuracy was assumed to indicate the high specificity of the index. The Bhattacharyya distances of carcinoembryonic antigen, neuron-specific enolase, alpha-feto protein, and CA724 were the largest, and those of CYFRA21-І, CA125, and UGT1A83 were the second largest. The specificity of the combination of the above seven indexes was higher than that of other combinations, and the accuracy of the established SVM identification model was high. Using Bhattacharyya distance detection and establishing an SVM model based on different serum marker combinations can increase diagnostic accuracy, providing a theoretical basis for application of mathematical models in cancer diagnosis.

Integrated bio-affinity nano-platform into a microfluidic immunosensor based on monoclonal bispecific trifunctional antibodies for the electrochemical determination of epithelial cancer biomarker.

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is a biomarker that is highly overexpressed on the surface of epithelial carcinoma cells. In this study, silver nanoparticles covered with polyvinyl alcohol (AgNPs-PVA) were synthesized, characterized and used in a microfluidic immunosensor based on the use of anti-EpCAM recombinant antibodies as a trapping agent. METHODS: The concentration of trapped EpCAM is then electrochemically quantified by HRP-conjugated anti-EpCAM-antibody. HRP reacted with its enzymatic substrate in a redox process which resulted in the appearance of a current whose magnitude (at a working voltage as low as -0.10V) is directly proportional to the concentration of EpCAM. RESULTS: Under optimized conditions, the detection limits for the microfluidic immunosensor and a commercial ELISA were 0.8 and 13.9pg/L, respectively. The within-assay and between-assay coefficients of variation are below 6.5% for the proposed method. The immunosensor was validated by analyzing patient samples, and a good correlation with a commercial ELISA was obtained. CONCLUSIONS: The good analytical performance is attributed to the efficient immobilization of the anti-EpCAM recombinant antibodies on the AgNPs-PVA, and its high specificity for EpCAM. This microfluidic immunosensor is intended for use in diagnosis and prognosis of epithelial cancer, to monitor the disease, and to assess therapeutic efficacy.

Antitumor Effects of Systemic DNAse I and Proteases in an In Vivo Model.

Background Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats,. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.

Serum uric acid as a surrogate marker of favorable response to bevacizumab treatment in patients with metastatic colon cancer.

Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.

Predictive factors of alcohol and tobacco use in adolescents / Fatores preditivos do uso de álcool e tabaco em adolescentes / Factores predictivos del uso de alcohol y tabaco en los adolescentes

OBJECTIVES: to analyze the effect of self-esteem, assertiveness, self-efficacy and resiliency on alcohol and tobacco consumption in adolescents. METHOD: a descriptive and correlational study was undertaken with 575 adolescents in 2010. The Self-Esteem Scale, the Situational Confidence Scale, the Assertiveness Questionnaire and the Resiliency Scale were used. RESULTS: the adjustment of the logistic regression model, considering age, sex, self-esteem, assertiveness, self-efficacy and resiliency, demonstrates significance in the consumption of alcohol and tobacco. Age, resiliency and assertiveness predict alcohol consumption in the lifetime and assertiveness predicts alcohol consumption in the last year. Similarly, age and sex predict tobacco consumption in the lifetime and age in the last year. CONCLUSION: this study can offer important information to plan nursing interventions involving adolescent alcohol and tobacco users. .

OBJETIVOS: analisar o efeito da autoestima, assertividade, autoeficácia e resiliência sobre o consumo de álcool e tabaco em adolescentes. MÉTODO: estudo descritivo correlacional com 575 adolescentes, realizado no ano 2010. Foram utilizadas a Escala de Autoestima, o Questionário de Confiança Situacional, o Questionário de Assertividade e a Escala de Resiliência. RESULTADOS: o ajuste do modelo de regressão logística, considerando a idade, sexo, autoestima, assertividade, autoeficácia e resiliência foi significante em relação ao consumo de álcool e tabaco. A idade, resiliência e assertividade foram preditores do consumo de álcool em algum momento na vida e a idade e a assertividade foram preditores no último ano. Para o consumo de tabaco, a idade e o sexo foram preditores em algum momento na vida e a idade no último ano. CONCLUSÃO: este estudo pode proporcionar informações importantes para o planejamento de intervenções de enfermagem em adolescentes usuários de álcool e tabaco .

OBJETIVOS: analizar el efecto de la autoestima, asertividad, autoeficacia y resiliencia sobre el consumo de alcohol y tabaco en adolescentes. MÉTODO: descritivo correlacional con 575 adolescentes, en 2010. Se utilizaron la Escala de Autoestima, el Cuestionario de Confianza Situacional, el Cuestionario de Asertividad y la Escala de Resiliencia. RESULTADOS: el ajuste del modelo de regresión logística, considerando la edad, sexo, autoestima, asertividad, autoeficacia y resiliencia, muestra significancia en el consumo de alcohol y tabaco. La edad, resiliencia y asertividad predicen el consumo de alcohol alguna vez en la vida y la edad y asertividad en el último año. De la misma forma la edad y sexo predicen el consumo de tabaco alguna vez en la vida y la edad en el último año. CONCLUSIÓN: este estudio puede proporcionar información importante para la planificación de intervenciones en enfermería de los adolecentes usuarios de alcohol y tabaco. .

El sistema lewis hoy. nuevos enfoques / The lewis system today. new approaches

La expresión de antígenos (Ags) Lewis depende de alelos heredados en loci independientes, el gen Secretor (SE) que codifica la fucosiltransferasa 2 (FUT2) y el gen Lewis (LE) que codifica la fucosiltransferasa 3 (FUT3). El gen Se codifica una glicosiltransferasa que adiciona una fucosa en la cadena precursora de tipo 1 formando el Ag H en secreciones y fluidos. Como los azúcares inmunodominantes del Ag A y B pueden ser agregados a la cadena H de tipo 1, la FUT2 también controla la expresión de Ag A y B en las secreciones. El gen se es un alelo no funcional. El gen Le codifica una transferasa diferente que adiciona una fucosa en el 2do carbono en el precursor de tipo 1. El alelo le no es funcional. Las FUT2 y FUT3 interactúan para la formación de Ags Lewis en secreciones y fluídos. Los Ags Lewis en los eritrocitos no son en realidad parte integral de la membrana, están adsorbidos sobre la superficie en forma pasiva a partir del plasma. Están ampliamente distribuidos en tejidos humanos, eritrocitos, endotelio, riñón, tracto genitourinario, epitelio gastrointestinal y son receptores para algunos patógenos. Los anticuerpos (Acs) anti-Lewis en general no son clínicamente significativos, aunque se han publicado algunos casos de reacciones transfusionales hemolíticas, enfermedad hemolítica fetoneonatal y rechazo de transplante renal. Este trabajo es una revisión sobre los Ags del Sistema Lewis enfocada hacia sus diferentes funciones biológicas y su importancia en campos variados fuera del Banco de Sangre y la Inmunohematología tradicional.

The expression of Lewis blood group antigens depends on the alleles inherited at independent loci, FUT2 Secretor gene (SE) and FUT3 Lewis gene (LE). The Se and Le alleles encode separate fucosyltransferases that interact to form Lewis antigens in secretions and fluids. The Lewis antigens on red blood cells are not integral to the membrane but are passively adsorbed from the plasma. The allele Se encodes a transferase that adds fucose to type 1 precursor chains in secretions and fluids to form type 1 H antigen. Because A and B terminal sugars may be added to type 1 H chains, FUT2 also controls A and B expression in secretions. The FUT2 allele se gen is a nonfunctional allele. The FUT3 allele Le encodes a transferase that adds a fucose in other position in type 1 H precursor. The FUT3 allele le gen is a nonfunctional allele. The Le antigens are widely distributed in human tissues and fluids and are receptors for some pathogenic organisms. Lewis antibodies are rare and clinically no significant, although there are some reports of hemolytic transfusion reactions, hemolytic disease of the newborn and renal transplant rejection. This review focuses on different biological functions of Lewis antigens and their importance in some fields other than Blood Banks and traditional.

[An elevated neutrophil/lymphocyte ratio is associated with poor prognosis in stage II resected colon cancer]. / Un índice neutrófilo/linfocito elevado se asocia a peor pronóstico en cáncer de colon etapa II resecado.

BACKGROUND: The neutrophil/lymphocyte ratio is an effective marker of inflammation ana can have prognostic value in surgical patients. AIM: To evaluate the effect of an increased neutrophil/lymphocyte ratio (NLR) on perioperative complications ana overall ana disease-free survival in patients undergoing elective resection for stage II colon cancer. MATERIAL AND METHODS: Data was obtained from clinical charts, preoperative blood results and hospital records of all patients undergoing an elective curative resection for colon cancer, between 2000 and 2007. Preoperative NLR was calculated. Follow-up was obtained from a prospectively maintained colorectal cancer database, clinical records and questionnaires. Uni and multivariable analysis were performed to identify associations, and survival analysis was performed using Kaplan-Meier curves. RESULTS: One hundred twenty two patients with a mean age of 69 years (52% males), were evaluated. Median follow-up was 73 months, and overall survival for 1 and 5 years was 95% and 68%, respectively. On a multivariable analysis after adjusting for age, sex, tumor depth invasion, use of adjuvant therapies and American Society of Anesthesiology preoperative risk score, an NLR > 5 was associated with an increased perioperative complication rate (odds ratio: 3.06, p = 0.033). Kaplan-Meier survival analysis showed a worse overall and disease-free survival for patients with NLR greater than five. CONCLUSIONS: A preoperative NLR of five or more is associated with greater perioperative morbidity and worse oncological outcomes in patients undergoing resection for elective stage II colon cancer.

Un índice neutrófilo/linfocito elevado se asocia a peor pronóstico en cancer de colon etapa II resecado / An elevated neutrophil/lymphocyte ratio is associated with poor prognosis in stage II resected colon cancer

Background: The neutrophil/lymphocyte ratio is an effective marker of inflammation ana can have prognostic value in surgical patients. Aim: To evaluate the effect of an increased neutrophil/lymphocyte ratio (NLR) on perioperative complications ana overall ana disease-free survival in patients undergoing elective resection for stage II colon cancer. Material and Methods: Data was obtained from clinical charts, preoperative blood results and hospital records of all patients undergoing an elective curative resection for colon cancer, between 2000 and 2007. Preoperative NLR was calculated. Follow-up was obtained from a prospectively maintained colorectal cancer database, clinical records and questionnaires. Uni and multivariable analysis were performed to identify associations, and survival analysis was performed using Kaplan-Meier curves. Results: One hundred twenty two patients with a mean age of69years (52% males), were evaluated. Median follow-up was 73 months, and overall survival for 1 and 5years was 95% and 68%, respectively. On a multivariable analysis after adjusting for age, sex, tumor depth invasion, use of adjuvant therapies and American Society of Anesthesiology preoperative risk score, an NLR > 5 was associated with an increased perioperative complication rate (odds ratio: 3,06, p = 0,033). Kaplan-Meier survival analysis showed a worse overall and disease-free survival for patients with NLR greater than five. Conclusions: A preoperative NLR of five or more is associated with greater perioperative morbidity and worse oncological outcomes in patients undergoing resection for elective stage II colon cancer.

Leucine-rich diet improves the serum amino acid profile and body composition of fetuses from tumor-bearing pregnant mice.

Pregnancy is a complex process that can be jeopardized when associated with cancer, because of the coexistence of two complex metabolic conditions: a fetus and cancer. The aim of this study was to evaluate fetal growth in association with cancer development as well as the indirect effects produced by tumors in pregnant mice subjected to a leucine-rich diet, knowing that leucine supplementation can minimize the tumor effects by acting as a cell signaling agent to improve the protein synthesis process. We evaluated fetuses (n = 6) from NMRI pregnant mice fed either a control or a leucine-rich diet in either the presence or absence of an MAC16 colon adenocarcinoma or ascitic fluid inoculation. The fetal serum amino acids were separated using high-performance liquid chromatography, and fetal cytokine levels were analyzed using a microsphere-based multiplex immunoassay (Luminex xMAP). Fetal body composition was measured as the water, fat, and protein total content and total serum protein, albumin, and glucose content. Tumor growth resulted in a severe reduction in fetal body weight and protein content and increased fetal resorption, associated with placental weight decrease; these effects were minimized by a leucine-rich diet. Serum total protein and glucose content were reduced in fetuses from tumor-bearing dams but were reverted by nutritional supplementation. The serum amino acid profiles differed significantly between the tumor-bearing mice fed with a leucine-rich diet and controls. Certain tumor effects were reproduced in fetuses from ascitic fluid-injected dams, suggesting indirect effects of tumor growth. We conclude that certain effects of tumor growth can be mimicked by ascitic fluid injection and can be modulated by a leucine-rich diet.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients.

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Análisis multivariado de factores clínicos y anatomopatológicos que determinan una elevación del antígeno carcinoembrionario en pacientes con cáncer de colon / Multivariate analysis of clinical and anatomopathological factors that determine an elevation of carcinoembryonic antigen in patients with colon cancer

El antígeno carcinoembrionario (ACE) es una glicoproteína que se encuentra en el endodermo primitivo y está ausente en la mucosa normal del adulto. Es usado como marcador tumoral en cáncer de colon, pero su utilidad es discutida. OBJETIVO: Evaluar la asociación del ACE preoperatorio con variables anatomopatológicas y de etapificación según TNM. MATERIALES Y MÉTODOS: Se revisaron 41 fichas clínicas de pacientes atendidos por cáncer de colon durante el año 2007 en el Hospital Clínico San Borja-Arriarán. La concentración sérica del ACE fue determinada mediante la técnica de inmuno-enzimoanálisis de micropartículas. Se utilizó el programa STATA9 para el análisis estadístico y se consideró significativo un p < 0.05. RESULTADOS: No existen diferencias entre las distintas localizaciones del tumor, histología, grado de diferenciación celular e invasión perineural, vascular y linfática del tumor.Se encontraron diferencias significativas en la etapificación según TNM. Tumores T1 poseen niveles menores que tumores T4; compromiso ganglionar N1 tiene niveles mayores que N2; el estadio1 tiene niveles menores que el estadio 3 y 4. CONCLUSIONES: El nivel plasmático de ACE preoperatorio tiene mayor correspondencia con variables de etapificación y no tiene asociación con variables anatomopatológicas, demostrando su utilidad en el proceso de etapificación clínica prequirúrgica. Sin embargo, se requieren estudios dirigidos para comprender la ventaja de este marcador como instrumento de etapificación.

The carcinoembryonic antigen (CEA) is a glycoprotein found in the primitive endoderm and is absent in normal adult mucosa. It is used as a tumor marker in colon cancer, but its usefulness is discussed. OBJECTIVE: To evaluate the association of presurgical ACE levels and pathological variables according to TNM staging. MATERIALS AND METHODS: 41 medical records were reviewed of patients seen per colon cancer in 2007 at the Hospital Clínico San Borja-Arriarán. STATA9 was used for statistical analysis and we considered significant p <0.05. RESULTS: There were not differences between tumor sites, histology, grade of cell differentiation and perineural, vascular and lymphatic invasion of the tumor. We found significant differences in the presurgical CEA levels according to TNM staging. T1 tumors have levels lower than T4 tumors; N1 lymph node involvement has greater levels than N2; stage 1 has smaller levels than the stage 3 and 4. CONCLUTIONS: The level of presurgical plasma CEA has higher correlation with staging variables than pathological variables, demonstrating its usefulness in the clinical staging process. However, studies are required aimed to understand the advantage of this marker as a means of staging.

Prognostic value of the detection of lymph node micrometastases in colon cancer.

INTRODUCTION AND OBJECTIVES: A study is made of the clinical repercussions of occult metastases-micrometastases (MMs+)-or isolated tumour cells (ITCs+) in the lymph nodes of patients with stage IIA and IIB colon adenocarcinoma initially considered as corresponding to N0. MATERIAL AND METHODS: A retrospective study of 39 patients with stage IIA and IIB (T3-T4 N0 M0) colon adenocarcinoma, subjected to similar surgical and adjuvant chemotherapy treatment, with long and careful follow-up (minimum: 5 years, mean: 81.7 months) was performed on their previously resected lymph nodes, with the aid of new histological and immunohistochemical (cytokeratin) sections, in order to detect MMs or ITCs. Disease-free survival (DFS) and global survival (GS) in the two groups (patients with MMs+ or ITCs+ vs. patients without MMs or ITCs) were compared at 5 years based on the corresponding Kaplan-Meier survival curves, with the Breslow test. RESULTS: A total of 382 lymph nodes from the 39 patients (mean: 9.8; standard deviation: 6.09) were revised. MMs+ were detected in 2 cases and ITCs+ in 2 more cases on the Cytokeratin study. GS of the whole series at 5 years was 89.74% (35 patients alive) with a DFS at 5 years of 79.49% (31 patients free of disease), but the 2 cases with MMs+ were dead at 5 years, with high statistical differences between both groups (MMs+/MMs-) (p<0.0001). When comparing the group of MMs+/ITCs+ patients and the group of MM-/ITCs- patients, the DFS and GS times at 5 years were higher in the MMs-/ITCs- group (p=0.0692 and p=0.006 respectively). CONCLUSIONS: Although the incidence of MMs+ or ITCs+ in the examined lymph nodes was low, the presence of MMs is related to a dramatic reduction in GS and DFS at 5 years. We encourage a detailed histological study of lymph nodes resected in patients with deep penetrating colon tumours in order to assure a pN0 status.

Valor pronóstico y predictivo de la timidilato sintetasa (TS) en pacientes con cáncer de colon / Prognostic and predictive value of the thymidylate synthase (TS) in patients with colon cancer

El cáncer colo-rectal es uno de los cánceres más comunes en el mundo actual, para lo cual el 5-Fluorouracilo (5-FU) es usualmente parte importante del tratamiento quimioterapéutico. La Timidilato Sintetasa (TS), es la enzima blanco para el 5-FU. Estudios recientes sugieren que la TS puede predecir el pronóstico y el éxito de la terapia basada en el 5-FU. El propósito de este estudio retrospectivo fue determinar la expresión de la TS en muestras de biopsias de cáncer de colon incluidas en parafina, mediante la técnica de inmunohistoquímica y correlacionarla con factores de riesgo, antígeno carcinoembrionario (CEA), CA-19-9, evolución del paciente y respuesta al tratamiento con 5-FU. La población en estudio consistió en 34 muestras de biopsias de cáncer de colon obtenidas de pacientes quienes fueron tratados con 5-FU y Leucovorina. A las muestras de adenocarcinomas colónicas incluidas en parafina se les realizó la detección de TS a través de inmunohistoquímica. Los pacientes en cuyos tumores había una alta expresión de la TS, mostraron una sobrevida significativamente menor comparado son aquellos pacientes que mostraron baja expresión de la enzima en sus tumores (p=0,004). La expresión de la TS puede ser utilizada como un importante marcador pronóstico de sobrevida y de respuesta a la quimioterapia en pacientes con cáncer colo-rectal.

Colorectal cancer is one of the most common cancers in the world today, for which a 5-fluorouracil (5-FU) is usually an important part of the chemotherapeutic treatment. The thymidylate synthase (TS), is the target enzyme for 5-FU. Recent studies suggest that TS can predict the prognosis and the success of therapy based on 5-FU. The purpose of this retrospective study was to determine the expression of TS in samples from biopsies of colon cancer in paraffin, using the technique of immunohistochemistry and its correlation with risk factors, carcinoembryonic antigen (CEA), CA-19-9, patients evolution and response to treatment with 5-FU. The study population consisted of 34 biopsy samples obtained from colon cancer patients who were treated with 5-FU and Leucovorin. A sample of colonic adenocarcinoma in paraffin was performed to detect TS through immunohistochemistry. Patients whose tumours had a high expression of TS showed a significantly lower survival rate compared with those patients who showed low expression of the enzyme in their tumours (p = 0.004). The expression of TS can be used as an important marker of survival prognosis and response to chemotherapy in patients with colon cancer.