Academic literature on the topic 'Tumori colon retto'

Leiomyosarcoma (LMS) of sigmoid colon is extremely rare high grade neoplasm with poor prognosis. Gastrointestinal leiomyosarcoma are aggressive mesenchymal tumors. Here we present an unusual case of leiomyosarcoma of sigmoid colon with adhesions and perforation in small intestine. Case presentation: A 65 years old male patient referred to our institute with complaints of vomiting, pain and distention of abdomen .Clinical examination showed rigidity and guarding of abdomen with diminished bowel sounds. Clinically diagnosed as intestinal obstruction. Colonoscopy revealed growth at recto-sigmoid junction. Histopathology of biopsy reported with differential diagnosis. Malignant gastrointestinal stromal tumors (GIST) and Leiomyosarcoma. Immunohistochemistry confirmed the final diagnosis. SMA positive and CD117 negative. Hence diagnosed as leiomyosarcoma of rectosigmoid colon. Conclusion: Colonic leiomyosarcoma is rare and its occurrence in rectosigmoid colon is unusual. Leiomyosarcoma can be differentiated from GIST by IHC marker.

Introducción: Los tumores sincrónicos son sumamente raros, la coexistencia de cáncer de colon y apéndice es un fenómeno relativamente inusual, que plantea problemas diagnósticos a la hora de discriminar la naturaleza primaria o metastásica de cada uno de ellos. Este hecho se suscita en la mayor parte de los casos ante adenocarcinomas mucosecretores sincrónicos. Reporte de caso: Presentamos el caso de una paciente femenina de 72 años de edad que ingresó al servicio de emergencia del Hospital Regional Docente Las Mercedes de Chiclayo por sintomatología de dolor abdominal agudo, donde se le realizan estudios imagenológicos con diagnóstico presuntivo de neoplasia maligna de recto, ingresando a sala de operaciones. El resultado anatomopatológico evidenció un diagnóstico de Adenocarcinoma tubular con componente mucinoso en recto-sigmoides de bajo grado de malignidad (moderadamente diferenciado), con invasión hasta tejido adiposo peri rectal adyacente, bordes de invasión infiltrativo e invasión perineural, con margen de resección libre y ganglios linfáticos libres de neoplasia maligna; además de, Adenocarcinoma mucinoso de apéndice moderadamente diferenciado (G2), de localización difusa, la neoplasia invade hasta la muscular propia, margen de resección libres de neoplasia maligna. Conclusión: La importancia de esta categoría es que la frecuencia de neoplasias malignas a nivel apendicular no es alta, y su asociación simultánea con Adenocarcinoma colorrectal las hace aún más insólitas.

El linfoma primario de recto es un tumor intestinal, poco frecuente, que está constituido, principalmente, por el tipo no Hodgkin extraganglionar y corresponde de 0,2% a 0,6% de todos los tumores de colon y recto. Se presenta el caso de una mujer de 79 años que consultó por una masa en recto de varios meses de evolución y rectorragia crónica. Se le tomó una biopsia, cuyo reporte histopatológico fue indicativo de linfoma no Hodgkin. El linfoma no Hodgkin de recto es un tumor raro, con pobre pronóstico, cuyo pilar de tratamiento es la cirugía. A continuación, se presenta el caso y una breve revisión de las características clínicas e imaginológicas de esta neoplasia poco frecuente.

3567 Background: The anatomical location of the primary tumor has been associated with outcomes in mCRC, with left-sided (L) tumors having a better prognosis than right-sided (R) tumors and location predicting response to treatment. REG significantly improved overall survival (OS) vs placebo in patients with mCRC who progressed on available treatments in 2 randomized, phase 3 trials (CORRECT, CONCUR). This exploratory analysis evaluated outcomes by primary tumor location in patients with mCRC treated with REG in the CORRELATE study. Methods: CORRELATE is an observational study designed to characterize the safety and effectiveness of REG in unselected patients for whom the decision to treat with REG has been made by the treating physician according to the local health authority label. Primary L tumors were located in the rectum, splenic flexure, recto-sigmoid, descending, or sigmoid colon; R tumors were in the appendix, hepatic flexure, cecum, or ascending colon. OS was analyzed by the Kaplan–Meier method and comparisons were by a 2-sided log-rank test. Results: Primary tumor location was available for 474 patients (L, n = 375 [79%]; R, n = 99 [21%]). Median time from initial diagnosis and from diagnosis of metastatic disease to treatment was slightly longer in L vs R tumors (32 vs 28 months and 25 vs 22 months, respectively). A higher proportion of patients with L vs R tumors, respectively, had prior radiotherapy (34% vs 13%) and a lower proportion had a partial colectomy (40% vs 70%). Best response to prior systemic therapy (partial response + stable disease) was 72% for L tumors and 68% for R tumors with a median duration of treatment of 26 and 22 months, respectively. REG treatment duration was similar in the 2 groups. Median OS (95% CI) was 6.7 months (6.1, 7.7) for L tumors vs 6.3 months (4.9, 8.1) for R tumors (P = 0.3); median progression-free survival (95% CI) was 2.8 months (2.6, 3.0) vs 2.6 months (2.4, 3.0) (P = 0.5), respectively. Conclusions: Interim results from this observational study suggest that OS is similar in patients with R and L tumors treated with REG. Clinical trial information: NCT02042144.

Introducción: Entre el 10 y 20% de los pacientes con cáncer colorrectal tratados con intento curativo, desarrollan metástasis pulmonares. La resección quirúrgica de las metástasis puede ser realizada en un grupo selecto de pacientes y representa el único tratamiento potencialmente curativo. Pacientes y métodos: Estudio retrospectivo de los pacientes con cáncer colorrectal que desarrollaron metástasis pulmonares, tratados de 1975 a 2003. Se efectuó un análisis descriptivo de las variables demográficas y se determinó el grado de asociación de cada una de las variables con la sobrevida libre de enfermedad y la sobrevida global. Resultados: Fueron incluidos 22 pacientes con una mediana de edad de 64 años, doce mujeres y diez hombres. La localización del tumor primario correspondió al colon derecho en un caso, colon izquierdo en ocho y recto en trece. Todos fueron adenocarcinomas; ocho de ellos bien diferenciados y catorce moderadamente diferenciados. El tratamiento consistió en cirugía en quince pacientes y quimioterapia-cirugía en siete. El procedimiento quirúrgico realizado fue metastasectomía en diecinueve pacientes y lobectomía en cuatro. Doce pacientes tuvieron solo una metástasis y el resto presentaron dos o más. Solo dos pacientes presentaron complicaciones postoperatorias mayores. No hubo muertes. Once pacientes desarrollaron recurrencia pulmonar y uno de ellos re-recurrencia pulmonar. La mediana de seguimiento fue de 37 meses. El porcentaje de la sobrevida global a 1, 3 y 5 años fue de 100, 85 y 69 %, respectivamente. En relación a la sobrevida libre de enfermedad, la única variable que mostró asociación estadísticamente significativa fue el grado histológico del tumor primario (p<0.045) y para la sobrevida global fue el número de metástasis (p<0.046). Conclusión: La metastasectomía pulmonar es una opción terapéutica con baja morbi-mortalidad que ofrece la posibilidad de curación en un grupo bien seleccionado de pacientes con cáncer colorrectal con enfermedad pulmonar metastásica.

The main aim of this work is to explore the relationship between survival to tumors and individual socio-economic characteristics and the Census tract where the considered persons reside. Cancer is, in fact, a chronic disease whose clinical history has a strong relationship with the socio-economic factors, in particular as regards access to medical care and the chance of a timely diagnosis, i.e. the factors that mainly influence the therapeutic results. The considered data are referred to the patients resident in the Umbria region. Women with breast cancer diagnosed in the period 1/1/2001-31/12/2010 (8,317 cases) and individuals of both genders with colorectal cancer diagnosed in the same period (12,087 cases) were considered. The follow-up of cases stopped to 31/12/2012, the most recent available data. We have chosen to study these tumors, because they are the most widespread in the Italian population and the literature has shown how the socio-economic characteristics of the patients affected by these cancers are associated with significant differences in their survival. For all patients we collected: data coming from the Umbrian Cancer Registry (CR) about variables that describe age, gender, status in life, diagnosis, tumor characteristics and treatment; individual socio-economic information about marital status, educational level and employment status, provided by every Umbrian municipality Registry; the variables that describe the socio-economic characteristics of the Census tract where every considered patient used to live (Census of Population and Housing 2001), made available by the Regional Statistics Office. The Umbria region was chosen for the high quality of the data that the regional information system can make available, in particular as regards the local CR, thanks to the strong operational integration that exists between the different data sources. The datasets for the considered diseases have been built by deterministic record linkage, which put in connection information from the CR with those from the municipal Registry Offices and the Census. It was possible to automatically link the data of 8,209 women with breast cancer (98.7% of the total) and 11,749 cancer patients of colorectal cancer (97.2% of the total). Manual procedures for the identification and correction of errors allowed to recover also the unrelated cases, reaching 100%. A multilevel mixed effects parametric survival model, which allowed to use all the individual and area variables as responsible for the fixed effects and the Census tract of residence as responsible for the random effects, was used for survival analysis. In addition to the effects generated by the medical variables, the results showed that marital status at the individual level will help to change the survival, with better chances of overcoming the disease for married than unmarried or widowed. This is obviously an indirect effect, which expresses the need for social and family support, also occurring at the area level for breast cancer, where the structural dependency index decrease the chances of survival. For colorectal cancer, however, the relevant area-wide variable is the ageing index. The results seem to confirm what was found by recent national and international studies, which attached to the social and family capital a particularly significant role in having an early diagnosis, properly following the care and thus improving the chances of surviving to cancer. It is, however, reduced the role of the socio-economic characteristics that traditionally are associated with health inequalities, i.e. the education level and the professional status.

Il cancro del colon-retto è una delle neoplasie più frequenti, ad alto tasso di mortalità, causato dall’interazione di fattori genetici e ambientali. Parallelamente al modello stocastico, secondo il quale tutte le cellule tumorali (CT) hanno una stessa probabilità di rigenerare un tumore, sta prendendo piede il modello che vede solamente in un piccolissimo sottogruppo di cellule staminali tumorali (CST) la capacità di dar luogo e sostenere la crescita tumorale. Dalla letteratura si evince come le CST mostrino deregolazioni a carico di geni implicati in: chemio-resistenza, transizione epitelio-mesenchimale (EMT), auto-rinnovamento incontrollato, processi peculiari delle CST, che favoriscono l’insorgenza di un fenotipo tumorale. Lo scopo del progetto di Dottorato è stato quello di isolare e caratterizzare le CST sia da linee cellulari tumorali che da biopsie di tumore al colon-retto, per identificare marcatori tumorali utili a delineare le fasi di progressione del tumore e di individuare potenziali bersagli terapeutici. Inoltre, ho sottoposto le CT e le CST di una linea di adenocarcinoma del colon-retto (HCA7), a trattamento con l’estratto naturale di T. cordifolia, pianta utilizzata della medicina Ayurvedica, ed uno dei suoi principi attivi, la berberina, allo scopo di verificarne l'efficacia antitumorale. Ho osservato importanti deregolazioni nelle popolazioni cellulari trattate, a carico di diversi geni coinvolti principalmente nella EMT, nella regolazione del ciclo cellulare e della apoptosi e nel favorire un fenotipo chemio-resistente. I livelli di espressione di questi geni sono risultati essere significativamente sotto-espressi, sia nelle CT trattate che nelle CST trattate. I risultati che ho ottenuto depongono a favore di un potenziale ruolo attivo della sostanza naturale sottoposta ad indagine, nel contrastare molti di quei processi fondamentali per lo sviluppo di un fenotipo tumorale. Inoltre, i miei dati avvallano anche l’ipotesi che vede le CST come potenziali bersagli terapeutici, per ottenere un effetto mirato su questa popolazione cellulare tumorale.
Colorectal cancer is one of the most frequent cancer, with a high mortality rate, caused by the interaction of genetic and environmental factors. Parallel to the stochastic model, according to which all tumor cells (CT) have the same probability of regenerating a tumor, there is a new model that look in a very small subset of cancer stem cells (CST) the responsible of tumor growth. In the literature, CSTs shows important deregulations on genes implicated in: chemo-resistance, epithelial-mesenchymal transition (EMT), uncontrolled self-renewal, peculiar processes of this small subpopulation, which favor the onset of a tumor phenotype . The aim of my PhD project was to isolate and characterize CSTs both from tumor cell lines and from colorectal cancer biopsies, in order to identify tumor markers useful for delineating the phases of tumor progression and identifying potential therapeutic targets. In addition, I treated the CT and CST of a line of colorectal adenocarcinoma (HCA7) with the natural extract of T. cordifolia, a plant used in Ayurvedic medicine, and one of its active ingredients, berberine, in order to verify its antitumor efficacy. I observed important deregulations in treated cell populations, dependent on several genes involved mainly in EMT, in cell cycle regulation and apoptosis, but also in promoting a chemo-resistant phenotype. The expression levels of these genes were found to be significantly under-expressed, both in the treated CTs and in the treated CSTs. The results I have obtained are in favor of a potential active role of the investigated natural substance, in countering many of those fundamental processes for the development of a tumor phenotype. Furthermore, my data also support the hypothesis that CSTs are potential therapeutic targets for the purpose of achieving a targeted effect on this cell tumor population.

El documento digital no refiere asesor
Determina los factores intraoperatorios y postoperatorios, que están asociados en la mayor sobrevida, en 20 pacientes intervenidos de metástasis Hepática de cáncer colorrectal, en el hospital Edgardo Rebagliati Martins con especial énfasis en los factores postoperatorios, que podrían informar acerca de la agresividad del tumor y de la eficacia curativa de la cirugía realizada. Se realizaó un estudio retrospectivo en 20 pacientes intervenidos de MHCCR entre Enero del 2002 y Diciembre de 2009, en el que analizamos factores de supervivencia preoperatorios, intraoperatorios y postoperatorios. El seguimiento fue de 55 ± 3 (intervalo, 12-124) meses. La mortalidad postoperatoria fue del 5% y la morbilidad, del 10%. Entre los factores preoperatorios analizados, la edad > 65 años y el tamaño de la metástasis > 5 cm fueron factores de mal pronóstico independientes, mientras que dos factores significativos de mal pronóstico fueron obtenidos del análisis postoperatorio: microsatelitosis y cifras postoperatorias de CEA > 5 ng/ml (al 1 mes). Se ha encontrado que el sexo, la localización del tumor primario, el tipo de resección, y localización de las metástasis y el CEA pre operatorio son factores que no tienen importancia pronóstica. Se concluye que la cirugía de la Metástasis Hepática ha demostrado ser segura y eficaz. Sin embargo, en pacientes con MHCCR es necesario tener en cuenta los factores postoperatorios que pueden informarnos acerca de la agresividad del tumor y de la eficacia de la cirugía.
Trabajo de investigación

Orientador : Prof. Dr. José Ederaldo Queiroz Telles
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Ciencias Biológicas (Microbiologia, Parasitologia e Patologia Básica). Defesa: Curitiba, 04/08/2009
Inclui referências : f. 102-111
Resumo: A capacidade de predizer a agressividade biológica pela identificação das vias carcinogenéticas através da análise tecidual é de valor inestimável para o tratamento dos pacientes com câncer. Se tumores não responsivos aos tratamentos usuais pudessem ser identificados, estes pacientes poderiam ser poupados da toxicidade terapêutica e, assim poderiam ser candidatos a novas modalidades terapêuticas não convencionais. Nesta pesquisa objetiva-se identificar as vias carcinogenética clássica (p53) e mutadora (MSI-H) e correlacionaá-las com o fenótipo neoplásico de 51 tumores colorretais esporádicos. Métodos: Blocos de tecidos fixados em formalina a 10% e incluídos em parafina foram submetidos a cortes histológicos de 4?, para avaliação histológica. A técnica de (TMAs) foi utilizada para uma melhor uniformidade e um menor custeio das reações imunoistoquímicas para detecção das proteínas de reparo hMLH1, hMSH2, hMSH6 e a proteína p53. Resultados: Nos 51 casos de CCR esporádico estudados, quanto à distribuição das características clínico-patológicas, observou-se que 57% eram do sexo masculino, 60% do tipo histológico tubular, 51% com grau de diferenciação moderado, 58,82% com profundidade de invasão da subserosa pT3 e estádio IIA com média de idade de 59,4 anos. Nesta pesquisa, 84,31% dos tumores apresentaram hiperexpressão da proteína p53 (p<0,05) e 27,50% apresentaram ausência das proteínas de reparo EPR - (p<0,05). Na análise imunoistoquímica das proteínas hMLH1, hMSH2 e hMSH6 observou-se ausência da imunoexpressão em 15,68%, 11,76% e 17,65% dos tumores respectivamente. Em 19,60% dos casos foram decorrentes da via carcinogenética mutadora (MSI-H) destes, 70% foram do gênero feminino, 90% do tipo não mucinoso e 80,% apresentavam localização preferencial no cólon distal com média de idade de 57,10 anos. Por outro lado 66,66% eram decorrentes da via carcinogenética clássica (p53+). Destes 61,76% foram do gênero masculino, 85,29% do tipo histológico não mucinoso e 88,24% apresentavam localização preferencial no cólon distal com média de idade de 60,55 anos. Conclusão: Nesta pesquisa as vias carcinogenéticas clássica e mutadora não ocorrem com a mesma freqüência, sendo que a via predominante na carcinogênese colorretal esporádica é a via clássica. Houve correlação significativa (p>0,05) entre as características patológicas e os marcadores imunoistoquímicos.
Abstract: The ability to predict the carcinogenetic biological aggressiveness by identifying the pathways through tissue analysis is invaluable for the treatment of patients with cancer. If tumors that are not responsive to usual treatments could be identified, patients could be spared the toxicity and therapy, thus could be candidates for new unconventional therapeutic modalities. This research aims to identify and correlate the phenotype of the neoplastic tumor carcinogenetic classic pathways (p53) and mutated (MSI-H) in 51 sporadic colorectal tumors. Methods: Blocks of tissues fixed in formalin at 10% and included in paraffin were subjected to histological sections of 4_ for histological evaluation. The technique of (TMAs) was used for better uniformity and Immunohistochemistry of the cost of repair proteins hMLH1, hMSH2, hMSH6 and p53. Results: Of the preliminary parameters, on the distribution of the 51 cases of sporadic CRC studied at the clinical and pathological characteristics, we observed that 57% were male, 60% of tubular histological type, 51% with moderate degree of differentiation, 58, 82% with depth of invasion of the sub-serousa PT3 and stage IIA with a mean age of 59.4 years. In this research, 84.31% of the tumors showed hyperexpression of P53 protein (p <0.05) and 27.50% showed absence of protein repair EPR - (p <0.05). In immunohistochemical analysis of the repair proteins hMLH1, hMSH2 and hMSH6 were observed absence of expression in 15.68%, 11.76% and 17.65% respectively. In 19.60% of cases were caused by the mutated carcinogenetic (MSI-H) they were 70 % female, 90% of non-mucinous type and 80% showed preferential localization in distal colon with average age of 57.10 years. While 66.66% were caused by the classic carcinogenetic (p53 +) they were 61.76% male, 85.29% of non-mucinous histological type and 88.24% had preferential location in the distal colon with a mean age of 60.55 years. Conclusion: In this study carcinogenetic as classical ways and mutated not occur with equal frequency and the predominant pathway in sporadic colorectal carcinogenesis is the classic way. There was significant correlation between pathological features and immunohistochemical markers.

Recentemente è stato identificato un nuovo antigene associato al carcinoma del colon retto (CRC), denominato colorectal tumor-associated antigen-1 (COA-1), riconosciuto dai linfociti T CD4+ in associazione a specifiche molecole MHC di classe II e codificato del gene UBXD5. In questo studio abbiamo valutato se COA-1 sia in grado di evocare una risposta immunitaria mediata da linfociti T tumore-specifici nei pazienti affetti da CRC e se tale antigene possa rappresentare un nuovo mezzo per disegnare protocolli di immunoterapia e un marker di progressione della malattia. A tale scopo, i PBMC isolati dai pazienti con CRC sono stati stimolati in vitro con l’epitopo immunogenico di COA-1441-460 (FSTFPPTLYQDDTLTLQAAG) e la risposta immunitaria, sia antigene che tumore specifica, è stata analizzata mediante rilevazione del rilascio di IFN-g, tramite saggio ELISPOT. In tal modo, è stato possibile isolare linfociti T specifici per COA-1 e tumorereattivi da tutti i pazienti HLA-DRb1*0402 o *1301 con malattia in progressione (7/7, stadio C e D di Dukes), ma non dai pazienti con tumore in fase iniziale (4/4, stadio A e B di Dukes). I linfociti T TAA-specifici hanno mostrato un fenotipo CD3+, CD4+, CD69+, CD45RA+, compatibile con quello del subset dei linfociti T di tipo effettore. Inoltre, la maggior parte di queste cellule ha evidenziato un’attività citotossica diretta nei confronti delle cellule tumorali positive per COA-1 e per gli specifici elementi di restrizione di classe II. Abbiamo anche verificato se una risposta specifica nei confronti di COA-1 potesse essere isolata dai PBMC dei pazienti con CRC mediante l’impiego di cellule dendritiche (DC) autologhe caricate con il lisato tumporale. I nostri dati indicano che linfociti T CD4+ specifici per COA-1 e dotati di reattività anti-CRC possono essere isolati mediante stimolazione in vitro dei PBMC sia con le cellule tumorali intatte sia con le DC pulsate con il lisato del tumore autologo, suggerendo che tale TAA sia in grado di generare una risposta immunitaria dominante diretta contro il CRC. In conclusione, i risultati di questo studio indicano che COA-1 può essere considerato un antigene rilevante per la risposta immunitaria anti-tumorale nei pazienti con CRC, dal momento che correla con la progressione della malattia, e ne suggeriscono un possibile impiego nei protocolli di immunoterapia per i pazienti affetti da CRC.
Recently, a new colorectal cancer (CRC)-associated antigen, denominated colorectal tumorassociated antigen-1 (COA-1), recognized by CD4+ T lymphocytes in a HLA class IIrestricted way and encoded by UBXD5 gene, was identified. In this study, we evaluated whether COA-1 can evoke a specific T cell-mediated response in CRC patients and whether this antigen can represent a tool to design new protocols of immunotherapy and a marker for the progression of the disease. Peripheral blood lymphocytes isolated from CRC patients have been in vitro stimulated with the immunogenic epitope of COA-1441-460 (FSTFPPTLYQDDTLTLQAAG) and the antigen- and tumor immunological response was analyzed by IFN-g ELISPOT assay. We could isolate COA-1 specific and tumor reactive T lymphocytes from all (n= 7) HLADRb1* 0402+ or *1301+ CRC patients with progressive disease (Dukes’ C and D), but not in patients (n= 4) with early stage tumor (Dukes’ A and B). Furthermore, these T lymphocytes had a CD3+CD4+CD69+CD45RA+ phenotype, compatible with the activated effector-type T cell subset, and most of them exerted cytotoxic activity against tumor cells expressing COA-1 and the specific MHC restriction elements. In addition, we have verified whether COA-1 specific reactivity could be isolated from PBMCs of CRC patients by the usage of autologous dendritic cells loaded with tumor lysate. Tumor reactive and COA-1 specific CD4+ T cells colud be isolated by in vitro stimulation of PBMCs either with intact tumor cells and with DC pulsed with tumor lysate, suggesting that this antigen can generate a dominant immunological response against CRC. In conclusion, the results of this study indicate that COA-1 can be a relevant antigen for the anti-tumor immune response in CRC patients, correlating with the progression of the disease, and suggest that this molecule is suitable for immunotherapeutic protocols of these patients.

Determina cuáles son los marcadores tumorales (MT) más utilizados en el monitoreo posquirúrgico de los pacientes con cáncer colorectal sometidos a resección quirúrgica y analizar su tendencia a la normalización, así como su utilidad para discriminar las recurrencias. Estudio de tipo cohorte retrospectivo en el cual se revisaron las historias clínicas de pacientes que fueron sometidos a cirugía resectiva por cáncer colorectal en el Hospital Militar Central “Luis Arias Schreiber”, durante el periodo Enero 2003-Diciembre 2007, con el objetivo de analizar los resultados del monitoreo por MT. Durante el periodo de estudio se registraron un total de 56 casos (61% varones, con una edad promedio de 67.9 ± 13.2 años) de pacientes con cáncer colorectal sometidos a cirugías resectivas. En la mayoría de los casos el cáncer se localizó en colon (83%), era de tipo carcinoma (98%) y se encontraba en estadíos IIIA (48%) o IV (39%) de la clasificación TNM. En el 53% de los casos no se dosó ningún MT en el prequirúrgico, siendo los marcadores más utilizados el ACE (41%) y el CA-19.9 (29%). En promedio durante el prequirúrgico se pudo observar que el número de MT utilizados fue significativamente mayor en el postquirúrgico que en el prequirúrgico (2.2± 0.6 vs 0.9 ± 1.1, p <0.001). En total se registraron 4 (7.1%) de recurrencias, registrándose diferencias significativas entre las medias de los MT pre y post quirúrgicos ACE (13.2 ± 21.3 vs. 83.8 ± 21.3, p <0.001), Ca-19.9 (28.9 ± 31.2 vs. 82.9 ± 84.8, p <0.001) y CA-72.4 (17.2 ± 22.6 vs. 235.5 ± 199.3, p <0.001). no encontrándose mayores diferencias entre los niveles pre y posquirúrgicos de los MT AFP (5.9 ± 7.9 vs. 2.9 ± 0.4, p =0.440) ni CA-125 (18.6 ± 21.3 vs. 10.0 ± 1.5, p =0.569). En la experiencia del Hospital Militar Central el ACE, es el marcador tumoral más utilizado en el seguimiento de los pacientes con cáncer colorectal sometidos a resección quirúrgica; el cual tuvo utilidad en identificar casos de recurrencia al año de seguimiento. El resto de marcadores tumorales no tuvieron utilidad significativa.
Trabajo académico

Background At present the only prognostic system routinely employed for the management of gastric cancer patients is the TNM staging classification, that identifies broad risk categories with a significant prognostic variability within each stage, which makes TNM a suboptimal predictive tool on the single patient basis. Only 10-20% of patients with liver metastases from colorectal cancer is resectable with radical intent and 60-70% will develop a relapse despite apparently curative surgery. Both these classes of patients therefore would benefit from additional treatments after surgery such as adjuvant chemotherapy. We need new prognostic factors that can identify patients at high risk to be submitted to treatment. Aim of the study To study circulating tumor cells by gene profiling the peripheral blood in order to identify prognostic biomarkers that add independent prognostic power to the conventional staging systems. This might allow for a better stratification of patients’ risk and thus a better therapeutic management of gastric cancer and metastatic colorectal cancer patients, especially in the adjuvant setting. Patients, materials and methods 70 patients, affected with gastric adenocarcinoma at different TNM stages of disease who underwent radical surgery and 50 patients undergoing liver resection for metastases from colorectal cancer (stage IV) were enrolled in the study. Immediately before surgery, a sample of peripheral blood was withdrawn from each patient. For each sample, RNA was extracted and utilized for quantitative real time PCR evaluation of the expression of the following genes: CK19, CEA, VEGF, and Survivin for gastric cancer patients; CK19, CK20, CEA, VEGF, EGFR, CD133 and Survivin for colorectal liver metastases patients. Univariate and multivariate survival analysis was performed to investigate on the prognostic role of these biomarkers. Results After stepwise variable selection, Cox multivariate analysis of survival showed a significant association between overall survival and both TNM stage ad Survivin gene expression levels in peripheral blood of gastric cancer patients, while multivariate analysis confirmed the statistically significant association between both the radical resection and the transcriptional levels of CD133 and overall survival in colorectal liver metastases patients. In addition, Survivin transcriptional levels were higher in patients with gastric cancer as compared to the calibrator reference (obtained from the peripheral blood of healthy donors) in 98.6% of cases; analogously, CK19 was upregulated in 97.1% of cases. These findings support the hypothesis that the peripheral blood gene profile might be utilized also as a diagnostic marker in gastric cancer. Concluding remarks The positive findings of this pilot study are the basis for larger prospective studies in larger groups of gastric cancer and colorectal liver metastases patients, aimed to validate the prognostic power of Survivin and CD33 expression in peripheral blood of these two groups, respectively. Moreover it would be interesting to further explore also the potential diagnostic value of the peripheral blood gene profile in gastric cancer.
Presupposti dello studio Attualmente l'unico sistema prognostico utilizzato in clinica per i pazienti con cancro gastrico è la stadiazione TNM, che crea classi di rischio con prognosi significativamente diversa, ma con un’alta variabilità del rischio all’interno delle singole classi, risultando così uno strumento prognostico non ottimale a livello di singolo paziente. Solo il 10-20% dei pazienti con metastasi epatiche da carcinoma del colon-retto (CRC) risulta resecabile con intento radicale e di questi il 60-70% svilupperà una recidiva nonostante l’intervento potenzialmente curativo. Entrambe queste classi di pazienti necessitano di trattamenti aggiuntivi alla chirurgia come la chemioterapia adiuvante. Sono quindi necessari fattori prognostici nuovi, che permettano di individuare i pazienti ad alto rischio da indirizzare alla terapia. Scopo dello studio Studiare le cellule tumorali circolanti, attraverso il profilo di espressione genica nel sangue periferico, per individuare fattori prognostici indipendenti, in modo da rendere migliore la stratificazione del rischio e di conseguenza la cura dei pazienti con adenocarcinoma gastrico e con metastasi epatiche da carcinoma del colon-retto, con particolare riguardo alla selezione dei pazienti da trattare con terapia adiuvante. Pazienti, materiali e metodi Nello studio sono stati inclusi 70 pazienti con adenocarcinoma gastrico in diverso stadio TNM sottoposti a gastrectomia con intento radicale e 50 pazienti con metastasi epatiche da CRC sottoposti a chirurgia. Prima dell’intervento chirurgico, a ogni paziente è stato eseguito un prelievo di sangue venoso periferico, se ne è estratto l’RNA totale ed il corrispondente cDNA è stato utilizzato per l’analisi di espressione genica mediante PCR quantitativa. Per i pazienti con carcinoma gastrico sono stati valutati i geni CK19, CEA, VEGF, Survivin; per i pazienti con metastasi epatiche da CRC sono stati valutati i geni CK19, CK20, CEA, VEGF, EGFR, CD133 e Survivin. Per valutare il ruolo prognostico di ogni marcatore sono state effettuate le analisi di sopravvivenza uni- e multivariata. Risultati All’analisi multivariata secondo Cox della sopravvivenza globale, dopo selezione stepwise, sono risultati fattori prognostici indipendenti per i pazienti con cancro gastrico la stadiazione TNM e l’espressione del gene codificante per Survivin, mentre per i pazienti con CRC metastatico sono risultati fattori prognostici indipendenti la radicalità dell’intervento e l’espressione di CD133 nel sangue periferico. Inoltre Survivin era maggiormente espressa nei pazienti con carcinoma gastrico rispetto al calibratore (ottenuto dal sangue di donatori sani) nel 98.6% dei casi; analogamente CK19 era maggiormente espressa nel 97.1% dei casi. Questi dati supportano la possibilità dell’utilizzo dell’espressione genica nel sangue periferico anche come marcatore diagnostico del carcinoma gastrico. Conclusioni I risultati positivi di queste analisi costituiscono la base per la conduzione di più ampi studi prospettici nelle due patologie considerate, al fine di poter validare il valore prognostico dell’espressione di Survivin e CD133 nel sangue periferico dei pazienti rispettivamente con carcinoma gastrico e con CRC metastatico. Sarebbe inoltre di sicuro interesse confermare il significato diagnostico del profilo genico del sangue periferico nel cancro gastrico.

BACKGROUND The number of patients with colorectal cancers (CRCs) invading the submucosa (pT1) resected during colonoscopy is increasing due to the screening. Such tumors are potentially metastatic, but only 15% of patients have nodal involvement. Histologic criteria currently used for selecting patients needing resection are imprecise and most patients are overtreated. Tumor infiltrating lymphocytes (TILs) and mismatch repair (MMR) status impact on CRC prognosis and could be risk factors of nodal metastasis. AIM To identify patients requiring completion surgery, the value of histologic variables, TILs, and MMR status as risk factors of nodal metastasis was investigated in screening detected and endoscopically removed pT1 CRCs. MATERIALS AND METHODS Histologic variables, CD3+ and CD8+ TILs, and MMR status were assessed in 102 endoscopically removed pT1 CRC. Univariate and multivariate analyses were used to evaluate the correlation with nodal metastasis. RESULTS Positive resection margin, evidence of vascular invasion and tumor budding, wide area of submucosal invasion, and high number of CD3+ TILs were associated with nodal metastasis in univariate analyses. Vascular invasion was statistically independent in multivariate analysis. Evidence of neoplastic cells in the vessels and/or at the excision border featured 5 out of 5 metastatic tumors and 13 out of 97 non-metastatic ones. CONCUSIONS Completion surgery should be mandatory only for patients with pT1 CRC with vascular invasion or with tumor cells reaching the margin. In all other cases, the treatment choice should be entrusted to the evaluation of the risk-benefit ratio of each patient considering the rarity of nodal metastasis.
INTRODUZIONE Il numero di pazienti con cancro colo-rettale (CCR) infiltrante la sottomucosa (pT1) rimosso durante colonscopia è in aumento per via dello screening. Tale tumore potenzialmente è già metastatico, ma solo un 15% di pazienti ha coinvolgimento linfonodale. I criteri istologi attualmente utilizzati per selezionare i pazienti che necessitino di una resezione di completamento sono imprecisi e la maggior parte dei pazienti subisce un trattamento eccessivo. I linfociti intra-tumorali (TILs) e lo stato del mismatch repair (MMR) condizionano la prognosi del CRC e potrebbero essere fattori di rischio di metastasi linfonodale. OBIETTIVO Per identificare i pazienti che necessitano di chirurgia di completamento, è stato valutato nei CRC pT1 identificati dallo screening e rimossi endoscopicamente il valore delle variabili istologiche, dei TILS e dello stato del MMR come fattori di rischio di metastasi linfonodale. MATERIALI E METODI Le variabili istologiche, i TILS CD3+ e CD8+ e lo stato del MMR sono stati valutati in 102 CRC pT1 rimossi endoscopicamente. Analisi univariate e multivariate sono state utilizzate per valutare la correlazione con la metastasi lindonodale. RISULTATI Il margine di resezione positive, la presenza di invasione vascolare e di budding tumorale, l'ampia area di invasione e l'elevato numero di TILs CD3+ erano associata alla metastasi linfonodale nelle analisi univariate. L'invasione vascolare era l'unica variabili indipendente all'analisi multivariata. La presenza di cellule neoplastiche intravascolari e/o a livello del margine di resezione caratterizzavano tutti e 5 i tumori metastatici e solo 13 tumori non metastatici su 97. CONCUSIONI La chirurgia di completamento dovrebbe essere indicata solo per i pazienti con un CRC pT1 con invasione vascolare o con cellule neoplastiche che raggiungono il margine di resezione. In tutti gli altri casi, la scelta del trattamento dovrebbe essere affidata alla valutazione del rapporto rischi-benefici di ciascun paziente tenendo in considerazione la rarità del coinvolgimento linfonodale.

Comparazione fra chirurgia open e laparoscopica ed analisi dei risultati a breve e lungo termine anche in una categoria di pazienti trattati per neoplasia del retto basso. Open versus laparoscopic study for digestive surgery and short and long term outcomes after treatment for low rectal cancer.

Introdução: Câncer de endométrio associado a radiação (do inglês radiation-associated endometrial cancer - RAEC) é um termo que designa tumores malignos do endométrio que surgem após irradiação para tratamento de tumores primários do útero em si ou de outros órgãos pélvicos adjacentes, como cérvix uterina, cólon, reto, ânus ou trato urinário. Estudos sugerem incidência de 0,5 a 0,8% de todos os cânceres de endométrio, que são considerados uma patologia rara. Esse tipo de câncer diferencia-se do de endométrio primário por apresentar fatores de pior prognóstico no momento do diagnóstico, tais como tipo histológico não endometrioide, tumores pouco diferenciados e estadiamento mais avançado. Relato: Descrevemos um caso de RAEC em uma paciente de 74 anos, com sintomas de constipação, perda ponderal e aumento do volume abdominal, imagem em ressonância magnética da pelve sugestiva de hematométrio e lesões vegetantes em superfície endometrial, com história de tratamento de câncer de colo uterino 11 anos antes com quimioterapia, radioterapia pélvica e braquiterapia. Paciente foi submetida a histerectomia total com salpingo-ooforectomia bilateral, biópsia de peritônio e lavado peritoneal. Laudo histopatológico da peça cirúrgica identificou tumor mulleriano misto maligno heterólogo de endométrio com focos de adenocarcinoma em peritônio, configurando estádio FIGO IVb. Conclusão: Os principais tipos histológicos associados ao RAEC são o carcinossarcoma (35%) e o carcinoma seroso papilar (26%). O período de latência entre a data da radioterapia até o diagnóstico é por volta de 14 anos. Cerca de 70% dos casos apresentam-se no estádio III a IV no momento do diagnóstico. A sobrevida média nesse tipo de câncer é significativamente pior quando comparada à de câncer de endométrio esporádico, com média em 24 meses de 50% e em 5 anos de 21%. A sintomatologia difere da de câncer de endométrio esporádico. É comum o surgimento de estenose cervical após a irradiação do útero, justificando por que o RAEC pode se apresentar com dor e aumento do volume abdominal sem sangramento transvaginal.