Molecular mechanism and treatment strategy of colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Peritoneal metastatic colorectal cancer (pmCRC) is common and has been considered as the terminal stage. The theory of "seed and soil" and "oligometastasis" are the acknowledged hypotheses of pathogenesis of pmCRC. In recent years, the molecular mechanism related to pmCRC has been deeply researched. We realize that the formation of peritoneal metastasis, from detachment of cells from primary tumor to mesothelial adhesion and invasion, depends on the interplay of multiple molecules. Various components of tumor microenvironment also work as regulators in this process. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been widely used in clinical practice as an established treatment for pmCRC. Besides systemic chemotherapy, targeted and immunotherapeutic drugs are also increasingly used to improve prognosis. This article reviews the molecular mechanisms and treatment strategies related to pmCRC.

Enfoque interdisciplinario en el manejo del cáncer de colon / The Interdisciplinary Approach in Colon Cancer Management

Introducción: El modelo interdisciplinario en el ámbito oncológico ha permitido la vinculación entre diferentes disciplinas lo que permite aportar soluciones para elevar la calidad de vida de los enfermos y proporcionan una atención de excelencia. Objetivo: Explorar la evidencia científica sobre la colaboración interdisciplinar en el tratamiento del cáncer de colon. Métodos: Se realizó una investigación de tipo sistemática. Se ejecutó una búsqueda digital en las bases de datos de Web of Science, Lilacs, SciELO, Latindex, Elsevier, PubMed, Medline y Google de publicaciones actualizadas en inglés y español. Desarrollo: El enfoque interdisciplinario en el tratamiento de las enfermedades oncológicas, entre ellas el cáncer de colon, se ha descrito desde hace algún tiempo. El diseño permite vincular diferentes especialidades en las interconsultas y en el propio acto quirúrgico, lo que redunda en la formulación de problemas de investigación que requieren para su solución el intercambio de conocimientos y tecnologías de una especialidad a otra, permite aportar soluciones para elevar la calidad de vida de los enfermos y proporciona una atención de excelencia. Conclusiones: El cáncer es una enfermedad que requiere una atención para el paciente, no solo dentro de la esfera biológica; también psicológica, social y espiritual. Los equipos interdisciplinares, formados por profesionales de distintas disciplinas, son una herramienta que puede ayudar, en gran medida, a conseguir una mejor atención(AU)

Introduction: The interdisciplinary model in the oncological field has permitted connection between different disciplines, allowing to offer solutions for raising the quality of life of patients and provide excellent care. Objective: To explore the scientific evidence on interdisciplinary collaboration in the treatment of colon cancer. Methods: A systematic research was carried out. A digital search was carried out in the Web of Science, Lilacs, SciELO, Latindex, Elsevier, PubMed, Medline and Google databases, in view of identifying updated publications in English and Spanish. Development: The interdisciplinary approach in the treatment of oncologic diseases, including colon cancer, has been described for some time. The design allows connecting different specialties during interconsultation or the surgical act itself, which results in the formulation of research problems that require, for their solution, the exchange of knowledge and technologies from one specialty to another, allowing to offer solutions for raising the quality of life of patients and provide excellent care. Conclusions: Cancer is a disease that requires care for the patient, not only within the biological sphere, but also in the psychological, social and spiritual aspect. Interdisciplinary teams, made up of professionals from different disciplines, are a tool that can help, to a great extent, achieve better care(AU)

The prognostic roles of PYCR2 and ZBTB18 expression in tissues of colorectal carcinoma and non-neoplastic tissues: an immunohistochemical study

Background: It is important to detect novel biomarkers responsible for the progression and spread of colorectal cancer (CRC) to better evaluate the prognosis of the patients, provide better management, and foster the development of therapeutic targets. In humans, pyrroline-5-carboxylate reductase 2 (PYCR2) is encoded on chromosome 1q42.12, and its metabolic activity has been linked to oncogenesis in many cancers. Zinc finger and broad-complex, tramtrack, and bric-à-brac (BTB) domain-containing protein 18 (ZBTB18), a zinc finger transcriptional repressor, has been found to have a tumor-suppressor role and to be methylated in CRCs. To date, the prognostic roles of PYCR2 and ZBTB18 in CRC patients have not been thoroughly studied. Objective: To evaluate the tissue protein expression of PYCR2 and ZBTB18 in CRC and adjacent non-neoplastic intestinal tissues, to detect their roles in CRC carcinogenesis, progression and metastases. Patients and methods: After applying the inclusion criteria, 60 CRC patients were included in the study. Tissue samples from the tumor and the adjacent non-neoplastic tissues were stained with PYCR2 and ZBTB18. The patients were followed up for about 30 months (range: 10 to 36 months). We performed a correlation regarding the expression of the markers, and clinicopathological and prognostic parameters. Results Upregulation of PYCR2 and downregulation of ZBTB18 were found to be higher in CRC tissue than in the adjacent non-neoplastic colonic mucosa (p = 0.026 and p < 0.001 respectively). High expression of PYCR2 and low expression of ZBTB18 were positively correlated with large tumor size, higher tumor grade, advanced tumor stage, presence of spread to lymph nodes, and presence of distant metastases (p < 0.001). High PYCR2 and low ZBTB18 expressions were significantly associated with poor response to therapy (p = 0.008 and 0.0.17 respectively), as well as high incidence of progression and recurrence (p = 0.005), and unfavorable overall survival (OS) rates (p = 0.001). Conclusion: High expression of PYCR2 and low expression of ZBTB18 were independent predictors of CRC, progression, poor prognosis and unfavorable patient OS and progression-free survival (PFS) rates. (AU)

The possibility of early diagnosis of colorectal cancer through expression of Lncrna UCA1, Lncrna LINC00970, and Wnt genes; an in-vitro study

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.

Sobrevida de pacientes com câncer colorretal em um Cancer Center / Survival of patients with colorectal cancer in a cancer center

ABSTRACT BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013.

RESUMO CONTEXTO: Estudos hospitalares recentes têm demonstrado aumento da sobrevida do câncer colorretal e melhor sobrevida para mulheres, jovens e pacientes diagnosticados em estágio precoce da doença. OBJETIVO: Descrever a sobrevida global e analisar os fatores prognósticos de pacientes tratados para câncer colorretal em um centro de oncologia. MÉTODOS: Foram incluídos pacientes com diagnóstico de adenocarcinoma de cólon e reto entre 2000 e 2013, identificados no Registro Hospitalar de Câncer do A.C.Camargo Cancer Center. A sobrevida global aos 5 anos foi estimada pelo método de Kaplan-Meier e os fatores prognósticos foram avaliados pelo modelo de Cox. As razões de risco (HR) são relatadas com intervalos de confiança (IC) de 95%. RESULTADOS: Dos 2.279 casos de câncer colorretal analisados, 58,4% eram de cólon. A taxa de sobrevida global aos 5 anos para pacientes com câncer colorretal foi de 63,5% (65,6% e 60,6% para câncer de cólon e retal, respectivamente). O risco de óbito foi elevado para pacientes na faixa etária de 50-74 anos (HR=1,24; IC95% =1,02-1,51) e ≥75 anos (HR=3,02; IC95% =2,42-3,78), para pacientes com câncer retal (HR=1,37; IC95% =1,11-1,69) e para aqueles cujo tratamento foi iniciado >60 dias após o diagnóstico (HR=1,22; IC95% =1,04-1,43). O risco diminuiu para pacientes diagnosticados em períodos recentes (2005-2009 HR=0,76; IC95% =0,63-0,91; 2010-2013 HR=0,69; IC95% =0,57-0,83). CONCLUSÃO: A sobrevida dos pacientes com câncer colorretal é maior naqueles em estágio inicial e com início do tratamento antes dos 60 dias.. Idade acima de 70 anos foi fator independente preditivo de mau prognóstico. A sobrevida global aumentou para todos os pacientes tratados no período de 2000-2004 a 2010-2013.

Assessment of prognosis in patients with stage II colon cancer / Avaliação o prognóstico de pacientes com cancer de colon no estadio II

Pathologic staging is currently the most important prognostic factor in colon cancer, although individually this procedure does not provide a complete clinical outcome. This study aimed to determine the disease-specific survival of patients with colon cancer treated in the Braga Hospital from January 2005 to December 2013, according to the American Joint Committee on Cancer, 6th edition, and the disease-free survival and disease- specific survival of high- and low-risk stage II patients, whether in use, or not, of adjuvant chemotherapy. We obtained a total sample of 578 patients, with 145 and 65 high- and low-risk stage II patients, respectively. We observed a 5-year disease-specific survival rate of 93%, 27.4% and 75% for stage IIA, IIB and IIIA patients, respectively, where IIIA and IIB present statistically significant differences (p = 0.001). In high-risk stage II patients, disease-free survival (p = 0.107) and disease-specific survival (p = 0.037) were higher in the group submitted to chemotherapy. In low- risk patients, disease-free survival was higher in the group submitted to chemotherapy (p = 0.494), while disease-specific survival was lower (p = 0.426). The differences observed between stage IIB and IIIA survival can be explained by the consensual use of adjuvant chemotherapy in stage IIIA, and by its controversial use in stage IIB. Adjuvant chemotherapy showed to be effective only in high-risk stage II patients in terms of disease-specific survival. In the future, other markers, namely molecular ones, may be used to stratify the risk of stage II patients and determine who will benefit from adjuvant chemotherapy. (AU)

O estadiamento patológico é, atualmente, o fator de prognóstico mais importante do câncer de cólon, embora individualmente não preveja totalmente o resultado clínico. Neste estudo, pretendeu-se determinar a sobrevivência para uma doença específica (SDE) dos pacientes com câncer de cólon tratados no Hospital de Braga entre janeiro de 2005 e dezembro de 2013, de acordo com a 6a edição da American Joint Committee on Cancer e a Sobrevivência Livre de Doença (SLD) e SDE dos doentes em estadio II, classificados em alto e baixo risco, de acordo com a realização ou não de quimioterapia adjuvante. Obtivemos uma amostra total de 578 pacientes, dos quais uma parcela pertencia ao estadio II de alto ou de baixo risco (145 e 65 pacientes, respetivamente). Observamos SDE a 5 anos de: 93%, 27,4% e 75% para os estadios IIA, IIB e IIIA, respetivamente; IIIA e IIB apresentaram diferenças significativas (p = 0,001). SLD (p = 0,107) e SDE (p = 0,037) para o estadio II de alto risco foram superiores no grupo tratado com quimioterapia. Nos doentes de baixo risco, SLD foi superior no grupo tratado com quimioterapia (p = 0,494), enquanto que SDE foi inferior (p = 0,426). As diferenças de sobrevivência observadas para os estadios IIB e IIIA podem se dever ao uso controverso da quimioterapia em IIB e ao uso consensual em IIIA. O uso da quimioterapia adjuvante demonstrou ser efetivo nos doentes em estadio II de alto risco em termos de SDE. Futuramente, outros marcadores, nomeadamente moleculares, poderão vir a ser uti- lizados para estratificar o risco do estadio II e definir quem se beneficiará com o tratamento adjuvante. (AU)

Cáncer de colon en el Hospital Nacional Luis N. Saénz - PNP del 2001 al 2012 / Colonic cancer in the National Hospital Luis N. Saenz - PNP from 2001 to 2012

OBJETIVOS: Describir la experiencia obtenida en el manejo de pacientes con Cáncer de Colon en el HNLNS PNP. METODOLOGIA: Se revisó las historias de 81 pacientes diagnosticados de Cáncer de Colon (CC) cuyas edades fluctuaban entre los 38 y los 90 años, tratados en el Departamento de Oncología y Hematología del HN LNS-PNP entre 2011 y 2012. RESULTADOS: La incidencia de CC en esta población cautiva es de 9 casos/100000 hab. Predomina en sexo masculino y entre los 45 y 75 años. El EC II fue relativamente el más frecuente y se le relacionó clínicamente con rectorragia y alteración del hábito defecatorio, mientras que en EC III y IV se relacionó con perdida ponderal. El adenocarcinoma es el tipo histológico más frecuente y el grado histológico fue predominantemente 2 y 3. La incidencia de poliposis asociada fue del 10 por ciento, a predominio de Colon izquierdo y del tipo adenoma velloso. Fueron operados en EC II el 90,3 por ciento, en EC III el 73,3 por ciento y en EC IV el 36,8 por ciento y recibieron quimioterapia en EC II el 71 por ciento, en EC III y IV el 100 por ciento. La supervivencia lograda después de 18 meses de seguimiento fue en EC II de 95 por ciento, EC III de 60 por ciento y en EC IV de 30 por ciento. La recurrencia fue más frecuente en EC III y la progresión en EC IV. Tanto la recurrencia como la progresión afectaron principalmente a hígado y peritoneo. Analizando el EC II según los criterios de riesgo se observó que los tres casos que recurrieron, pertenecen al grupo de alto riesgo, siendo los criterios más frecuentes invasión linfovascular o peineural y la presencia de menos de 12 ganglios en la pieza operatoria. CONCLUSIONES: El cáncer de Colon en la población de estudio tiene una incidencia similar a la del resto del país. La localización del tumor se correlaciona con la sintomatología y con el Estadío Clínico. Tanto el grado histológico alto, los estadíos clínicos tardíos y la presencia de criterios de alto riesgo, en pacientes en EC II...

OBJECTIVE: To describe the experience obtained in the management of patients with cancer of colon treated in HNLNS-PNP. METHODOLOGY: We review 81 histories about 81 patients diagnosed with cancer of colon (CC). Their ages were among 38 and 90 years old. They were treated in Oncology and Hematology Department of HN LNS-PNP on 2011 and 2012. RESULTS: The incidence of CC in that captive population was 9 cases/100000pp. It is most frequent in males and patients among 45 and 75 years old. EC II was the most frequent and it was related with rectorragy and defecation habitÆs alteration, while that of EC III and EC IV were more related with weight loss. Adenocarcinoma was the most frequent histology type and its histology grade was predominantly 2 or 3. The incidence of associated Polyposis was 10 per cent predominance of left side Colon. They were operated, in EC II 90.3 per cent, in EC III 73.3 per cent and in EC IV 36.8 per cent. They received chemotherapy, in EC II 71 per cent, EC III and EC IV 100 per cent. The successful surveillance after 18 months of following was: in EC II 95 per cent, in EC III 60 per cent and in EC IV 30 per cent. The recurrence was most frequent in EC III and the progression was in EC IV. Both affected recurrence and progression mainly to liver and peritoneal layer. Analyzing EC II according to the hazard criteria, we observed that the 3 cases recurred, belonged to the high risk group. The most frequent hazard criteria were: lympho-vascular or perineural invasion and, less of 12 ganglions in surgical piece. CONCLUSIONS: The Colon Cancer in the population studied has similar incidence like the rest of our country. The localization of the primary tumor is correlated with the symptomatology and clinical stage. The high histological grade, the late clinical stages and the presence of hazard high criteria, all those are correlated with more possibility of recurrence or progression. Although the multidisciplinary treatments were done according...

Ressecções eletiva e de urgência para tratamento de neoplasia maligna do cólon em hospital universitário: estudo de 66 casos / Elective and urgency resections for the treatment of colon neoplasm in University Hospital: study of 66 cases

O câncer de cólon é uma doença de alta prevalência e mortalidade, cujo tratamento baseia-se na ressecção cirúrgica. A possibilidade de cura aumenta com o diagnóstico precoce, daí a importância dos programas de rastreamento populacional do câncer colorretal. O presente estudo analisou, retrospectivamente, 66 pacientes submetidos a ressecções do cólon por neoplasia em um período de 58 meses no Hospital Universitário da Universidade de São Paulo. Os pacientes foram divididos em dois grupos: grupo 1, submetidos a cirurgia eletiva (28 pacientes), e grupo 2, submetidos a cirurgia de urgência (38 pacientes). Os grupos foram comparados com relação às variáveis sexo, idade, apresentação clínica, aspectos da técnica cirúrgica, sítio anatômico da lesão, estádio patológico, taxas de complicações, permanência hospitalar pós-operatória e óbitos na internação. Verificou-se no presente estudo que a idade entre os grupos foi semelhante. Houve uma predominância do sexo masculino entre os pacientes operados de urgência. No grupo de cirurgia eletiva, o principal sintoma foi a hematoquezia, enquanto os operados na urgência, tinham como principal queixa dor abdominal. A grande maioria dos pacientes, no momento da cirurgia, apresentava-se sintomática há meses. Os pacientes operados na urgência apresentaram mais tumores pT4 e os operados eletivamente apresentaram mais neoplasias em estádio I. Em ambos os grupos, o caráter oncológico dos procedimentos foi preservado, bem como foi alto o índice de anastomoses primárias (81,8 por cento). As taxas de complicações pós-operatórias, o tempo de permanência hospitalar pós-operatório e a mortalidade foram semelhantes.

Colon cancer is a disease with high frequency and mortality rates, which treatment is based, fundamentally, on surgical resection. Because early diagnosis increases the curability, it is essential to have a screening programs offering early treatment. A retrospective study was performed, including 66 patients who underwent colonic resections due to cancer, for 58 months at Hospital Universitario of Universidade de São Paulo. These patients were divided in two groups, group 1, submitted to elective surgery (28 patients), and group 2, submitted to emergency surgery (38 patients). The groups were comparable for gender, age, clinical presentation, surgical procedure techniques, tumor distribution, TNM stage, morbidity, postoperative hospital stay and postoperative mortality. No difference was observed in patients’age. Males were predominant in the urgency surgery group. Lower gastrointestinal bleeding was the main symptom in the elective group, whereas abdominal pain was the main symptom in the urgency group. Mostly of the patients were having symptoms for months at the time of surgery. Urgency group patients presented more pT4 tumors, and elective group patients presented more stage I cancer. In both groups the oncologic approach was achieved, as well as primary anastomosis rates (81.8 percent). No differences in average hospital stay, hospital morbidity or postoperative mortality were recorded.

Tratamiento adyuvante en cáncer de colon: nuestra experiencia / Adjuvant treatment for colon cancer: our experience

El cáncer de colon es uno de los tumores más frecuentes en nuestro país. Posterior a cirugía, la quimioterapia adyuvante ha mostrado beneficios para los pacientes de alto riesgo y ganglios positivos, por lo que es considerada estándar. De este estudio, es evaluar la experiencia de nuestra institución en lo que a esta modalidad de tratamiento se refiere durante cinco años. De manera preliminar, se evaluaron un total de 118 pacientes. La distribución por género fue igual. Los tumores de colon izquierdo ocuparon el mayor porcentaje (45,76%), la histología más frecuente fue adenocarcinoma. En cuanto al TNM, el T más frecuente fue el T3 (53.1%) y el N el NO (46,9%). El 63,2% de pacientes recibió quimioterapia adyuvante, siendo los esquemas más utilizados, Folfox 4 62,5% seguido de Xelos 18,1% y Capecitabina 13,9. El 66,7% presentó eventos adversos. siendo las más frecuentes diarreas, nauseas, vómitos, y neuropatía periférica, todos G1/2 en la mayoría de los casos. No hubo muerte asociada al tratamiento. El 100% de los pacientes tuvieron seguimiento y para el año 2009 el 55,93% se encontraban vivos. La sobrevida global fue mayor en el grupo que recibió adyuvancia sin llegar a significancia estadística (P=0,098) ya que hasta la fecha no se ha alcanzado la mediana de sobrevida global. La sobrevida libre de enfermedad, fue mayor en el grupo que recibió quimioterapia, alcanzado significancia estadística (P=0,045).

Colon cancer is one of the most common tumors in our country. Following surgery, adjuvant chemotherapy has shown benefit for patients at high risk and node-positive, so it is considered standard modality. The aim of this study is to evaluate the experience of our institution as far as this treatment modality, referred for five years. Preliminary we evaluated total of 118 patients, the gender distribution was equal. Left colon tumors, occupied the highest percentage (45.76%) and the most common histology was adenocarcinoma. With regard to TNM, T3 was the most frequent (53.1%) and N0 also (46.9%). Of the sample assessed, 63.2% received adjuvant che motherapy, being the most widely used schemes, Folfox 4 62.5 %, Xelox18.1% and Capecitabine 13.9%. 66.7% of patients had adverse events, being the most frequent diarrhea, nausea, vomiting, and peripheral neuropathy, all G1/2 in most cases. There were no treatment-related deaths. 100% of patients had follow-up, for the year 2009, 55.93% of them were alive. The OS was greater in the group that received adjuvant treatment with regard to that it did not receive it, without statistics significant (P=0.098) since up to the date there has not been reached the median of global survival. Similar results were obtained with regard to the DFS, being this major in the group that received chemotherapy, versus the group that did not receive it, reached significant statistics (P=0.045).

[Study of apoptosis induced by calendula officinalis extract on experimental colon carcinoma in rats]

In vitro studies have demonstrated the anticancer effect of Calendula officinalis extract on tumor cell line derived from colorectal cancers. The inhibition ranged from 70-100%. The aim of this study was to evaluate the apoptosis in epiththelial displastic colon cells following treated with Calendula officinalis extract. In this experimental study, 56 wistar male rats with age of 12 weeks and 200-300g weight were allocated into two equal groups of treatment and control. For induction of colorectal carcinoma, these two groups were given 1, 2-dimethylhydrazine [40mg/kg], as subcutaneous injection, twice a week for two weeks. Treatment group also was treated with Calendula officinalis extract [200mg/kg/day] orally for 10 weeks. After 10 weeks, distal parts of colon tissue were biopsied in both groups and 3-4 micron tissue section was prepared through TUNEL staining method. Immunohistopathological study reveals that apoptotic cells of displastic colon epithelial cells in treatment group were higher than control group. Mean difference between treatment and control groups were statistically significant [p<0.01]. This study indicated that Calendula officinalis extract would be induced apoptosis of displastic colon cells in experimental colorectal carcinoma of rats

Cáncer de colon recurrente: intervalo libre de enfermedad y tratamiento adyuvante / Recurrent colon cancer: disease free interval and adjuvant treatment

Objetivo: Determinar el intervalo libre de enfermedad” y su relación con el tratamiento adyuvante aplicado con intención curativa a los pacientes operados de cáncer de colon. Métodos: Se realizó un estudio descriptivo, observacional y prospectivo sobre el intervalo libre de enfermedad en 68 pacientes después de intervenidos de cáncer de colon en el Hospital Provincial Docente Saturnino Lora de Santiago de Cuba desde 1990 hasta el 2008, que presentaron recurrencia tumoral, diagnosticada en consulta externa mediante un esquema de seguimiento posoperatorio durante un quinquenio o más. Resultados: La monoquimioterapia con 5- fluoruracilo como tratamiento adyuvante proporcionó mejores resultados en los pacientes que recibieron 6 ciclos terapéuticos, pues en este grupo, ninguno recidivó antes del año de operado, por cuanto es el único que alcanza un intervalo libre de enfermedad por más de cinco años. La localización anatómica no fue un factor influyente en el citado intervalo. Conclusiones: El tratamiento adyuvante adecuado con 5-fluouracilo guardó relación con el intervalo libre de enfermedad más prolongado. Se impone incrementar la vigilancia de los pacientes intervenidos de cáncer de colon con intención curativa en los 2 primeros años de seguimiento posoperatorio, porque durante ese bienio se produce la mayoría de las recurrencias en cualquier localización.

Objective: To determine the disease free interval and its relationship with the applied adjuvant treatment with healing intention to the operated patients of colon cancer. Methods: a descriptive, observational and prospective study was carried out on the disease free interval in 68 patients after having surgical treatment of colon cancer in Saturnino Lora Teaching Provincial Hospital of Santiago de Cuba from 1990 to 2008 that presented tumorous recurrence, diagnosed in outpatient department by means of a posoperative follow up outline during a five year period or more. Results: The monoquimiotherapy with 5-fluoruracilo as adjuvant treatment provided better results in the patients that received 6 therapeutic cycles, because in this group, none repeated before the year of being operated, whereas is the only one that reaches a disease free interval for more than five years. The anatomical localization was not an influential factor in the mentioned interval. Conclusions: The appropriate adjuvant treatment with 5-fluouracilo kept relationship with the long lasting disease free interval. It is imposed to increase the surveillance of the operated patients due to colon cancer with healing intention in the first 2 years of posoperative follow up, because during that biennium most of the recurrences take place in any localization.

effects of resveratrol and tannic acid on apoptosis in colon adenocarcinoma cell line

To investigate the effects of resveratrol and tannic acid on apoptosis, and Bcl-2 homologous antagonist/killer [Bak] and fas associated death domain [FADD] proteins in the CaCo-2 cell line. In the present study, resveratrol and tannic acid were administrated in the CaCo-2 cell line at doses of 25, 50, and 100 uM. The CaCo-2 cells were grown and cultured in the Medical Biology Department, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. The effects of these agents on apoptotic index were determined by Apop Taq peroxidase kit and their effects on the ratios of Bak and FADD proteins by the immunohistochemical staining method at 24, 48, and 72 hours. Stained and non-stained cells in 30 separate areas of the 3 separate chamber slides, prepared for each group, were counted. The percentage of apoptosis, and Bak and FADD proteins was calculated with the control. Mean +/- standard error values were calculated for the 3 experiments. Apoptotic index, Bak protein percentage ratio, and FADD protein percentage ratio values in all groups that received tannic acid and resveratrol increased when compared within the groups. This increase was found to be time and dose independent in all parameters. Cells undergo apoptosis in 2 pathways [mitochondrial and death receptor] in resveratrol and tannic acid induced CaCo-2 cells

Colonic bilharzioma; surgical intervention versus conservative treatment

Bilharzioma implies a localized mass of fibrous and inflammatory tissue, which usually contains many eggs, frequently involving serosa and mesentery. Bilharzioma is probably caused by reaction to numerous eggs produced by one or more pair of worms in a single site. The aim of this study is to compare between surgical intervention and conservative treatment in a group of patients had colonic bilharzioma presented with abdominal masses and intestinal obstruction. Ten patients presented with abdominal masses and intestinal obstruction. Complete blood count, urine analysis and stool analysis done to all the patients of the study. Abdominal ultrasonogiaphy done in all the patients of the study. Abdominal computed tomography done in 6 patients. Barium enema done in 5 patients. All the patients of the study had been subjected to laparotomy. There were 7 males and 3 females, their ages ranged from 8 to 42 years [mean 14.2 years]. All the patients had abdominal pain [100%], 6 patients presented with abdominal mass [60%], and 4 patients presented with intestinal obstruction [40%]. There was microcytic hypachromic anemia in 9 patients [90%] and leukocytosis with eosinophilia in 7 patients [70%]. Abdominal US revealed presence of lymphoma versus teratoma in 6 patients [60%] and signs of intestinal obstruction in 4 patients [40%]. Barium enema revealed presence of multiple polyps throughout rectosigmoid colon, with loss of haustrations and spasm of descending colon in 3 cases. Colonic wall thickening with narrowing and rigidity of the ascending colon in 2 cases. Abdominal CT revealed presence of colonic wall masses suggestive of lymphoma in 6 cases. In laparotomy, there were 4 rectosigmoid bilharzioma, bilharzioma of the transverse colon down to the upper rectum in 3 patients and ascending colonic bilharzioma in 3 cases. Histopathology confirmed presence of bilharzial granuloma in all surgical specimens. Always consider bilharzioma in differential diagnosis of abdominal masses and intestinal obstruction, especially in countries where it is endemic.Biopsy is a must as clinical examination laboratory and radiological methods are not diagnostic

Imunogenicidade do vírus vacina recombinante modificado com o gene do antígeno cárcino-embrionário (CEA) humano em modelo experimental de adenocarcinoma de cólon / Immunogenicity of recombinant vaccinia virus modified with human carcinoembryonic antigen gene in an experimental model of colon adenocarcinoma

Introdução: Os adenocarcinomas do trato gastrointestinal desenvolvem inicialmente a partir do epitélio superficial, e em mais de 90% dos casos, expressam o CEA. Existe compartimentalização e alguma independência entre o sistema imunológico mucoso e sistêmico com tráfego assimétrico de células entre eles. Um melhor conhecimento da imunologia dos tumores tem gerado o desenvolvimento de várias abordagens de vacinas direcionadas contra antígenos tumorais específicos. O vírus vaccinia esta entre os mais potentes para a indução de resposta protetora em animais contra infecções virais e câncer. Este tem sido mostrado como imunogênico em humanos. Imunização com o vírus vaccinia recombinante com o antígeno carcinoembrionário (CEA) pode gerar proteção humoral e celular contra tumores CEA +, dependo da dose e via de imunização... Objetivos: Comparar a imunização intra-retal com a venosa, e a resposta ao nível sistêmico e local apos uma dose e dois reforços por estas duas vias. Desenvolvimento de um animal híbrido que desenvolva tumores espontâneos do trato gastrointestinal com evolução previsível:... Material e Métodos: Os animais foram imunizados intra-retal ou intravenoso com 10 milhões de partículas do vírus Vaccinia recombinante com o CEA a cada 15 dias totalizando 3 doses. O grupo controle recebeu a mesma imunização com o mesmo vetor porem, não transduzido com o CEA... Os tumores foram medidos a cada 2 dias. Os animais Apc foram gerados por manipulação genética através da desativação do gene da Polipose colônica adenomatosa (APC) com mutação induzida na posição do aminoácido 1648, gerando proteína instável e não funcional... O camundongo Apc/CEA é um relevante modelo animal para o estudo do desenvolvimento espontâneo do câncer de colón da fase de displasia ao adenocarcinoma invasivo...(AU)

Introduction: The adenocarcinomas of the gastrointestinal tract (TGI) develop from superficial epithelium and in more than 90% of cases express CEA. There is compartmentalization with some independence among mucosal versus systemic immune systems and the asymmetric trafficking of cells between them. An improved understanding of tumor immunology has led to the development of several vaccine approaches targeted against specific human tumors antigens. Recombinant vaccinia virus vaccines are among the most potent for inducing protective immunity in animais against many viral infections and cancer. They have been shown to be immunogenic in human. Immunization with recombinant carcinoembryonic antigen (CEA) vaccinia virus can generate humoral and cellular protection against tumors CEA+, depending on the dose and route of administration. One of the major obstacles in vaccine development has been the lack of a relevant animal model for appropriately evaluating vaccine agents and immunization protocols. These results could be more accurate using an animal model that mimics the human situation with development of spontaneous tumors from the gastrointestinal tract with high expression of a specific antigen. Objectives: Comparing intra-rectal and venous immunization, and to evaluate systemic and local immune response after one dose and 2 booster after these routes. Development of a hybrid mouse model that generates spontaneous TGI' s tumors with expected evolution: hyperplasia ~ dysplasia ~ adenoma ~ superficial adenocarcinoma ~ invasive adenocarcinoma. The animal model should have high CEA expression in tumors and low at normal tissues as observed in humans. Material e Methods: Animais had intra-rectal (IR) or endovenous immunization with 10 million units of recombinant vaccinia-CEA virus each 15 days in a total of 3 doses. Control had the same immunization routes with vaccinia virus without CEA expression. Half of the animais were sacrificed 7 days after the last immunization to evaluate the induction of an immune response against CEA at the spleen (systemic response) and at the Payer's patches (mucosa! response). Subcutaneous colon tumors, with or without the expression of CEA, were implanted in the other animais. Tumors were measured every 2 days. Animais Apc were generated by genetic manipulation with partia! knock out of the APC (Adenomatous Polyposis coli) gene at the amino acid position 1648. The Apc pro te in was unstable and not functional. The CEA mo use recei ved the complete human CEA DNA. Those 2 transgenic and knock out mice models were crossed generating a hybrid transgenic animal model with spontaneous development of TGI' s tumors with high expression of CEA. Results: The animais immunized with rVac-CEA presented humoral and cellular specific CEA response and some tumor protection for CEA + tumors.The contrai group immunized without CEA had no immune response or protection when challenged with CEA tumor implants. Intra-rectal immunization showed to be similar to intravenous immunization, with systemic and mucosa! responses but low-grade tumor protection. Some immunized animais were tumor free and ali were able to generate cytolytic activity against CEA+ cells. Among those that developed tumor, these were smaller and had decreased growing rate. Immunization did not show protection when animais received CEAtumors indicating specificity. The double transgenic animais presented at 2 months hyperplasic polyps and occult blood in the feces. At 4 months old they showed gastrointestinal polyps that progressed to invasive adenocarcinomas with a similar pattem of dysplasia and CEA expression as observed in human colorectal cancer. Tumoral tissues had high expression of human CEA and tissues like colon, intestine and stomach also expressed CEA but at low levei. These animais exhibited incomplete or partial tolerance to CEA. Conclusions: Intra-rectal immunization with rVac-CEA showed an immune response bigger than 40%. CTL against CEA after intra-rectal and systemic immunization was present at the spleen and Peyer' s patch. Both route of immunizations induce CEA + tumors protection but the EV route was more effective for subcutaneous tumor. The Apc/CEA mouse is an important animal model for the studying of spontaneous cancer colon development from the dysplasia to adenocarcinoma. The human CEA is over expressed in tumors of these animais. This model represents a system to evaluate different treatment options and induction of tolerance and tumor immunity (AU)