Identification of Biomarkers for Non-small-cell Lung Cancer Patients Treated With an Immune Checkpoint Inhibitor.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have an important role in lung cancer therapy. Although the programmed cell death protein-1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden are known prognostic factors, they are insufficient to predict clinical outcomes. This study was conducted to identify novel biomarkers for ICI treatment. PATIENTS AND METHODS: We performed univariable and multivariable analyses of 110 patients with advanced non-small-cell lung cancer (NSCLC) who were treated with an ICI to identify novel biomarkers related to prognosis. We assessed their backgrounds, such as performance status (PS), PD-L1 TPS, smoking status, and peripheral white blood cell counts at baseline and on the day the second course of ICI administration. RESULTS: In the multivariable analysis, PS, driver gene, immune-related adverse events, and post-treatment absolute neutrophil counts (post-ANCs) were significantly associated with progression-free survival. CONCLUSION: A high level of post-ANCs was associated with poor outcome in ICI-treated NSCLC patients.

Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer.

PURPOSE: We examined the prognostic impact of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) detected at the time of surgery in 742 untreated patients with early breast cancer. EXPERIMENTAL DESIGN: DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) assay. CTCs in blood were enumerated either by IE/FC or CellSearch. Median follow-up was 7.1 years for distant recurrence-free survival (DRFS) and 9.1 years for breast cancer-specific survival (BCSS) and overall survival (OS). Cox regressions were used to estimate hazard ratios for DRFS, BCSS, and OS in all patients, as well as in hormone receptor-positive (HR-positive, 87%) and HR-negative (13%) subsets. RESULTS: In multivariate models, CTC positivity by IE/FC was significantly associated with reduced BCSS in both all (n = 288; P = 0.0138) and HR-positive patients (n = 249; P = 0.0454). CTC positivity by CellSearch was significantly associated with reduced DRFS in both all (n = 380; P = 0.0067) and HR-positive patients (n = 328; P = 0.0002). DTC status, by itself, was not prognostic; however, when combined with CTC status by IE/FC (n = 273), double positivity (CTC+/DTC+, 8%) was significantly associated with reduced DRFS (P = 0.0270), BCSS (P = 0.0205), and OS (P = 0.0168). In HR-positive patients, double positivity (9% of 235) was significantly associated with reduced DRFS (P = 0.0285), BCSS (P = 0.0357), and OS (P = 0.0092). CONCLUSIONS: Detection of CTCs in patients with HR-positive early breast cancer was an independent prognostic factor for DRFS (using CellSearch) and BCSS (using IE/FC). Simultaneous detection of DTCs provided additional prognostic power for outcome, including OS.

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer

Purpose. Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients. Methods. In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model. Results. Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death-alive status with follow-up time (P < 0.0001). Conclusions. Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial (AU)

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Role of C16, angiopoietin-1 and regeneration gene protein 2 in attenuating inflammation in an experimental rat model of autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits. Our results demonstrated that triple combination therapy was more efficient than the monotherapy in EAE treatment. The triple therapy significantly delayed the onset of motor symptoms, reduced disease severity, attenuated inflammatory cell infiltration and suppressed the secretion of proinflammatory cytokines. Additionally, treatment increased anti-inflammatory cytokines expression, inhibited reactive astrocytes proliferation, reduced demyelination and axonal loss, and finally reduced the neural death. Specifically, Reg-2 administration rescued oligodendrocytes and neuronal axons mainly by direct neurotrophic effects, while C16+Ang-1 (C+A) mainly improved the inflammatory milieu. In conclusion, our study suggests a possible synergistic effect through targeting a variety of pathways in relieving the clinical symptoms of inflammation in acute EAE model. Therefore, using molecules that target different molecular pathways can be beneficial for exploring novel therapeutic approaches for MS treatment.

Evaluación diagnóstica de las masas anexiales. Actualización 2016 / No disponible

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Actualización del sistema Gleason y de otros datos patológicos pronósticos en el cáncer prostático: carga tumoral / Update of the Gleason system and other prognostic pathological data in prostate cancer: Tumor load

No disponible

Genomic profiling for copy number changes in plasma of ovarian cancer patients - a new era for cancer diagnostics?

A blood test that can detect human malignancy with high clinical sensitivity and specificity is highly desirable. To achieve this, a tumor marker is needed that correlates with tumor burden and that can be measured with high analytical sensitivity and specificity. Over the past decades, a number of different types of tumor markers have emerged, including proteins such as enzymes, glycoproteins, and oncofetal antigens. Besides proteins, genetic abnormalities such as mutations, amplifications, and circulating tumor DNA have served as tumor markers. Despite the diversity of such biomarkers, their acceptance and implementation into routine clinical practice requires that their use results in improvements in patient outcome. Current tumor markers used in the clinic have limited utility. As such, innovative approaches to identifying tumor markers are highly desirable and one such approach may be to look for sub-chromosomal changes in the blood of patients with ovarian cancer, as is routinely performed in prenatal screening.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0667-6.

Marcadores tumorales / Tumor markers

Los marcadores tumorales son moléculas (generalmente glucoproteínas), que pueden estar elevadas en presencia de un cáncer, bien como reacción del huésped ante el tumor o bien como producto del propio tumor. Estas moléculas, cuya concentración sérica también depende de la variabilidad biológica del paciente, son detectables en diferentes fluidos biológicos. La utilidad de los marcadores tumorales viene determinada por la sensibilidad y especificidad de cada uno de ellos. No existe un marcador tumoral 100 % sensible y específico. Un marcador tumoral con una alta sensibilidad sería aquél que se encuentra elevado en la mayoría de los pacientes que presentan una determinada neoplasia, mientras que la especificidad vendría dada por aquellos pacientes con niveles normales del marcador tumoral que no presentan ningún tipo de neoplasia. Así, los marcadores con altos valores de sensibilidad y especificidad permitirían detectar a los pacientes que padecen cáncer y diferenciarlos de individuos sanos o de pacientes que presenten patologías benignas. Podemos decir que, en general, debido a la falta de una elevada sensibilidad y especificidad diagnósticas, los marcadores tumorales no sirven para la detección temprana de las neoplasias, pero sí ayudan a la confirmación de un diagnóstico ya establecido por métodos más sensibles. La mayoría de ellos tienen además un valor pronóstico en el momento del diagnóstico, ya que su concentración se relaciona con el tamaño tumoral. Su verdadero valor clínico reside, sin embargo, en el seguimiento de los pacientes, tanto para detectar una recidiva temprana, como para evaluar la efectividad del tratamiento instaurado. Nos proponemos en esta revisión hacer un repaso de los marcadores tumorales más utilizados en nuestra práctica clínica y de algunas recomendaciones que se han consensuado sobre la indicación de determinación de los mismos en diversos tumores (AU)

Tumor markers are molecules (usually glycoproteins), the levels of which may be elevated in the presence of a cancer, either as a host's reaction to the tumor or as a product of the tumor itself. These molecules, whose serum concentration also depends on the biological variability of the patient, are detectable in different biological fluids. The usefulness of tumor markers is determined by the sensitivity and specificity of each of them. There is no tumor marker which is 100% sensitive and specific. A tumor marker with a high sensitivity would be the one that is elevated in the majority of patients who present certain neoplasm, whereas specificity would be determined by those patients with normal levels of the tumor marker who do not present any type of neoplasm. Thus, markers with high levels of sensitivity and specificity would allow for the detection of patients with cancer, and for their differentiation from healthy individuals or from patients with benign pathologies. We can say that, in general, due to the lack of high diagnostic sensitivity and specificity, tumor markers are not helpful for an early detection of neoplasms, but they do help to confirm a diagnosis already established by more sensitive methods. Most markers also have a prognostic value at the time of diagnosis, since their concentration is related to tumor size. However, their true clinical value lies in patient monitoring, both for detecting early recurrence and for evaluating the effectiveness of the established treatment. Our aim is to review the tumor markers most commonly used in our clinical practice, as well as some agreed recommendations on the indication of their determination in various tumors (AU)

(68)Ga-DOTA-peptide: A novel molecular biomarker for nasopharyngeal carcinoma.

BACKGROUND: Increased somatostatin receptor (SSTR) expression in patients with undifferentiated nasopharyngeal carcinoma (NPC) has been demonstrated with receptor autoradiography, (111) In-Octreotide scintigraphy, and (68) Ga-DOTA-TOC positron emission tomography (PET)/CT imaging. We sought to compare and correlate the uptake of fluorodeoxyglucose (FDG) and DOTA-NOC in undifferentiated NPC to ascertain the possible role of (68) Ga-DOTA-NOC PET/CT as a new imaging biomarker and to assess whether targeted peptide receptor radionuclide therapy is a feasible treatment option. METHODS: After obtaining approval from our institutional review board, 4 patients with biopsy proven nonkeratinizing undifferentiated NPC who had just undergone routine staging/restaging (18) F-FDG PET/CT imaging were prospectively and consecutively recruited for (68) Ga-DOTA-NOC PET/CT imaging. Of these 4 patients, 3 were newly diagnosed with untreated NPC, whereas 1 patient was diagnosed with a case of recurrent NPC with previous treatment. These patients subsequently underwent (68) Ga-DOTA-NOC PET/CT within 10 days from the (18) F-FDG PET/CT to ensure lesion comparability. Tracer uptake in tumor lesions were assessed visually and semiquantitatively by measuring maximum standardized uptake values (SUVmax). RESULTS: There were 12 FDG-avid lesions of which 7 showed avid uptake of DOTA-NOC greater than liver uptake, whereas 5 showed low uptake of DOTA-NOC less than liver uptake. Subset analysis of the FDG-avid lesions at the primary and recurrent sites showed that all the FDG-avid primary tumors in the nasopharynx showed avid uptake of DOTA-NOC. On the contrary, the case of recurrent NPC showed avid FDG uptake but low DOTA-NOC uptake. Subset analysis of the suspicious FDG-avid cervical lymph nodes showed that 50% of them demonstrated avid DOTA-NOC uptake greater than liver uptake, whereas the remaining demonstrated low-grade DOTA-NOC uptake less than liver uptake. The 2 subcentimeter cervical lymph nodes that showed low-grade uptake of FDG lower than mediastinal blood pool activity were deemed to be reactive/inflammatory and showed low-grade uptake of DOTA-NOC. CONCLUSION: This study highlights the potential of (68) Ga-DOTA-peptide PET/CT as a new molecular biomarker for newly diagnosed undifferentiated NPC, and less so for recurrent NPC and metastatic nodes. This potentially opens up new diagnostic and therapeutic options in the management of undifferentiated NPC.

Recombinant Reg3α protein protects against experimental acute pancreatitis in mice.

Regenerating gene 3α (Reg3α) protein is a trophic factor that stimulates cell and tissue proliferation, neogenesis and also acts against apoptosis and necrosis. In order to explore the potential roles of recombinant Reg3α (rReg3α), we produced a mature rReg3α polypeptide for direct administration in l-arginine (L-Arg) induced acute pancreatitis (AP) in mice. Our results showed that rReg3α stimulated cell proliferation through Erk1/2 and p38 phosphorylation and also cyclin D1 upregulation mediated by Akt/ATF-2 signaling. Moreover, rReg3α administration significantly reduced the pancreatic damage caused by L-Arg injection, as shown in histological examination and serum amylase, lipase and C-reactive protein (CRP) assays. Not only acinar cell necrosis but also apoptosis found in the pancreas of AP mice were alleviated by rReg3α. Finally, upregulated Bcl-2 and Bcl-xL and suppressed poly (ADP-ribose) synthetase/polymerase (PARP) levels were detected as being relevant to the mechanism of rReg3α protection. We therefore conclude that rReg3α acts as a protective polypeptide against AP in mice by enhancing Bcl-2 and Bcl-xL expressions and suppressing PARP level.

Impacto de la aplicación de un protocolo para el uso adecuado y seguro de marcadores tumorales / Impact of the implementation of a protocol for the adequate and safe use of tumor markers

Fundamento y objetivo: Los marcadores tumorales (MT) son pruebas accesibles para la actividad clínica. Su uso inadecuado puede provocar pruebas complementarias innecesarias para confirmar o refutar un resultado positivo. Tras 2 acontecimientos adversos por un uso incorrecto de MT, se implementó un protocolo para el uso adecuado y seguro de estos. El objetivo de este trabajo fue determinar el impacto de la implementación de dicho protocolo. Material y método: Estudio pre-postintervención. Se analizó el uso, durante un año, de peticiones de MT (antígeno carcinoembrionario, CA15.3, CA19.9, CA125) de pacientes no sometidos a revisión oncológica. Se implementó un protocolo, formándose a los facultativos según las recomendaciones del Grupo Europeo de Marcadores Tumorales, limitando su uso al seguimiento de la enfermedad y monitorización de tratamientos. Período estudiado: 2010-2014. Resultados: El número total de peticiones descendió un 50,81%, y el porcentaje de adecuación de los MT aumentó anualmente desde un 31,03 hasta un 77,91%. Conclusiones: La implantación de un protocolo del uso adecuado de MT contribuye a un uso seguro, evitando estudios no indicados y evitando pruebas complementarias innecesarias y lesivas para el paciente (AU)

Background and objetive: Improper clinical use of tumor markers (TM) may cause unnecessary additional studies to confirm or refute a positive result. After observing 2 adverse events due to a wrong use of TM, a protocol for improving their use was implemented. The objective of this study was to determine the impact of the implementation of the protocol. Material and method: This was a pre-postintervention study, where analytical requests of carcinoembryonic antigen, CA15.3, CA19.9 and CA125 were analyzed during one year in patients not undergoing checking of neoplasia. A protocol was implemented and physicians were trained as recommended by the European Group on Tumor Markers, limiting its use to monitor the disease and its treatment. The study period was 2010-2014. Results: The total number of requests dropped 50.81% and the percentage of adequacy of TM increased, each year, from 31.03 to 77.91%. Conclusions: The implementation of a protocol for the proper use of TM contributes to a safer use, avoiding incorrect studies and unnecessary and harmful tests for the patient (AU)

Effect of novel chitosan-fluoroaluminosilicate resin modified glass ionomer cement supplemented with translationally controlled tumor protein on pulp cells.

Dental materials that can promote cell proliferation and function is required for regenerative pulp therapy. Resin modified glass ionomer cement (RMGIC), a broadly used liner or restorative material, can cause apoptosis to pulp cells mainly due to HEMA (2-hydroxyethyl methacrylate), the released residual monomer. Recent studies found that chitosan and albumin could promote release of protein in GIC while translationally controlled tumor protein (TCTP) has an anti-apoptotic activity against HEMA. The aim of this study was to examine the effect of chitosan and albumin modified RMGIC (Exp-RMGIC) supplemented with TCTP on pulp cell viability and mineralization. Exp-RMGIC+TCTP was composed of RMGIC powder incorporated with 15 % of chitosan, 5 % albumin and supplemented with TCTP mixed with the same liquid components of RMGIC. The effect of each specimen on pulp cells was examined using the Transwell plate. From the MTT assay, Exp-RMGIC+TCTP had the highest percentages of viable cells (P < 0.05) at both 24 and 74 h. Flow cytometry revealed that, after 24 h, Exp-RMGIC+TCTP gave the lowest percentages of apoptotic cells compared to other groups. There was no difference in alkaline phosphatase (ALP) activity among different formula of the specimens, while cells cultured in media with TCTP had higher ALP activity. Von Kossa staining revealed that RMGIC+TCTP, and Exp-RMGIC+TCTP had higher percentages of calcium deposit area compared to those without TCTP. It was concluded that Exp-RMGIC supplemented with TCTP had less cytotoxicity than RMGIC and can protect cells from apoptosis better than RMGIC supplemented with TCTP.

Long-term follow up with sparing surgery for testicular diseases: a safe choice in benign testicular lesions

ObjetivoLlevamos a cabo una evaluación a largo plazo del tratamiento quirúrgico de conservación testicular en situaciones benignas.Material y métodosEntre enero de 2001 y Enero de 2005, realizamos un estudio clínico perspectivo de un único centro en nuestro Servicio Académico de Urología. Se examinaron las historias clínicas de todos los pacientes diagnosticados de masa testicular pequeña (menor de 1,5 cm) tratados con cirugía conservadora. Los pacientes fueron sometidos a exploración física, valoraciones de marcadores hormonales y tumorales, ultrasonidos escrotales y abdominales, radiografías pectorales y evaluación endocrinológica. En los casos de diagnóstico de enfermedad benigna o de situación maligna seleccionada (tumor de células de Leydig) durante el análisis de secciones, se llevó a cabo una cirugía conservadora. Los pacientes que presentaron una situación maligna fueron sometidos a un estricto seguimiento oncológico, conforme a las Pautas de la EAU.ResultadosDe enero de 2001 a enero de 2005, 80 pacientes con masa testicular pequeña fueron sometidos a cirugía conservadora. La edad media de los pacientes fue de 40,9 años. El seguimiento medio fue de 95,78 meses. Los pacientes presentaron, bien un nódulo testicular palpable (77,5%), bien un nódulo diagnosticado mediante ultrasonidos (22,5%). El diagnóstico tras el examen de secciones congeladas fue de tumor de células de Leydig en 20 de los 80 casos. El tamaño histológico medio del nódulo fue de 0,93 cm. Los marcadores tumorales fueron normales antes y después de la cirugía. Se realizó un seguimiento de todos los pacientes con malignidad de acuerdo con las Pautas de la EAU. No se observaron recidivas locales ni metástasis. El 100% de los pacientes sigue con vida.ConclusionesLa cirugía de conservación testicular es factible en todos los casos benignos. Los tumores de células de Leydig presentan un seguimiento favorable a largo plazo cuando se diagnostican tempranamente. La cirugía conservadora ha demostrado ser la elección más segura (AU)

Objective. We performed a long-term evaluation of testicular conservative surgical treatment of benign conditions. Material and methods. Between January 2001 and January 2005, a single center perspective clinical study was performed at our Academic Department of Urology. Case files of all patients diagnosed with small testicular mass (less than 1.5 cm) and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumor marker assays, scrotal and abdominal ultrasound, chest X-ray and endocrinological examination. Should a benign disease or a selected malignant condition (Leydig cell tumor) be diagnosed during the frozen section analysis, testicular sparing surgery was performed. Each patient presenting a malignant condition underwent a strict oncological follow up according to the EAU Guidelines. Results. From January 2001 to January 2005, 80 patients with small testicular mass underwent conservative surgery. Patient mean age was 40.9 years. Mean follow up was 95.78 months. Patients presented either with a palpable testicular nodule (77.5%) or a nodule diagnosed by ultrasound (22.5%). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 80 cases. Mean histological size of the nodule was 0.93 cm. Tumor markers were normal before and after surgery. Follow up was conducted for all malignant patients following EAU Guidelines. No local recurrence or metastasis were observed. 100% of patients are still alive. Conclusions. Testicular Sparing Surgery is feasible in all benign cases. Leydig cell tumors present a favorable long-term follow up when diagnosed early. Conservative surgery proved to be the safer choice (AU)

Distribución fenotípica del carcinoma de mama en Venezuela / Phenotypic distribution of breast carcinoma in Venezuela

Objetivos. Determinar la distribución de los diferentes fenotipos tumorales del carcinoma mamario en pacientes venezolanas. Caracterizar las variables clinicopatológicas en cada subgrupo y establecer los patrones de supervivencia para cada fenotipo. Pacientes y métodos. Se evaluaron de forma retrospectiva los datos de 266 pacientes con diagnóstico de carcinoma de mama y estudio inmunohistoquímico de la biopsia inicial. Las pacientes fueron clasificadas en 3 grupos de fenotipos tumorales (receptor estrogénico positivo, HER2/neu sobreexpresado y triple negativo). Se determinaron y correlacionaron variables epidemiológicas, clínicas y patológicas.ResultadosLos grupos de fenotipos tumorales estuvieron distribuidos en receptor estrogénico positivo con un 60,9%, triple negativo con un 27,8% y HER2/neu sobreexpresado con un 11,3%. El 92% de las pacientes con fenotipo triple negativo eran de raza negra. La mejor supervivencia correspondió al fenotipo receptor estrogénico positivo, y la peor, al fenotipo triple negativo, aunque las diferencias no fueron significativas. ConclusionesLa distribución fenotípica del cáncer de mama en Venezuela es parecida a la de la literatura general. El subtipo triple negativo, que tuvo la peor supervivencia, aunque no de forma significativa, presentó una incidencia más elevada que la de otros grupos poblacionales. La mayoría de las pacientes en este subgrupo eran de raza negra (AU)

Objectives. To determine the distribution of the distinct breast carcinoma phenotypes in Venezuelan patients, characterize the clinicopathologic variables in each subgroup, and establish survival patterns for each phenotype. Patients and methods. We retrospectively evaluated data from 266 patients diagnosed with breast carcinoma and an immunohistochemical study of the initial biopsy. The patients were classified into 3 groups of tumor phenotypes (estrogen receptor-positive, HER2/neu overexpression and triple-negative). We determined and correlated epidemiological, clinical and pathological variables. ResultsT. he tumor phenotype groups were distributed as follows: estrogen receptor-positive in 60.9%, triple-negative in 27.8%, and HER2/neu overexpression in 11.3%. A total of 92% of the patients with triple-negative phenotype were African American. Survival was best with the estrogen receptor-positive phenotype and worst with the triple-negative phenotype, but these differences were not significant. Conclusions. The phenotypic distribution of breast carcinoma in Venezuela is similar to that reported in the general literature. The incidence of the triple-negative subtype, which showed the worst survival –although this result was not significant– was higher than in other populations. Most patients in this subgroup were African American (AU)

Utilidad de los marcadores tumorales como cribado de neoplasia oculta en enfermedad tromboembólica / Role of tumour markers for occult neoplasia screening in thromboembolic disease

Objetivo: Evaluar la eficacia de los marcadores tumorales (MT) dentro del cribado avanzado para la detección de neoplasia oculta, en pacientes que han presentado enfermedad tromboembólica (ETE). Material y métodos: Estudio retrospectivo entre enero 2007 y diciembre de 2008 diagnosticados de ETE en nuestro centro. Se evaluaron los siguientes marcadores tumorales: antígeno carcinoso 19.9 (Ca 19.9), antígeno carcinoso 125 (Ca 125), antígeno carcinoso 15.3 (Ca 15.3), antígeno carcinoma embrionario (CEA), alfafetoproteína(AFP) y antígeno específico de próstata (PSA), tomando una determinación dentro del mes siguiente del diagnóstico de ETE. Criterios de inclusión: TVP de MMSS o MMII, TEP diagnosticados por prueba de imagen, clínica aguda. Criterios de exclusión: neoplasia previa conocida, TVP no idiopática, imposibilidad de seguimiento. Resultados: El 63,4% eran hombres, el 36,6% mujeres, con edad media de 62,8 años. El análisis estadístico se hizo en función de 122 pacientes, de los 199 iniciales, con un seguimiento medio de 38 meses. Al finalizar el estudio no se encontraron diferencias significativas en cuanto a la incidencia posterior de neoplasia respecto a los pacientes con valores de MT positivos de los negativos (Ca 125: p=0,161; Ca 15.3: p=0,930; CEA: p=0,703; PSA: p=0,382; AFP: 100% pacientes con valores negativos). Exceptuando el Ca 19.9 (p<0,000). Conclusiones: Como conclusión a nuestro estudio, el uso de MT como cribado de cáncer oculto posterior a un evento trombótico, no ha permitido la detección de los pacientes que desarrollaron una neoplasia durante el seguimiento (AU)

Objective: To evaluate the use of the tumour markers (TM) as part the advanced screening of occult neoplasia, in patients with thromboembolic disease (TED). Material and methods: A retrospective study was conducted between January 2007 and December 2008 on patients diagnosed with TED in our centre. The sample included 63.4% males, and 36.6% females, with a mean age of 62.8 years. The following TM were evaluated in a blood sample taken within one month after the diagnosis of TED: cancer antigen 19.9 (Ca 19.9), cancer antigen 125 (Ca 125), cancer antigen 15.3 (Ca 15.3), embryonic carcinoma antigen (CEA), alpha fetoprotein (AFP), and prostate specific antigen (PSA). The inclusion criteria were, DVT of lower and upper limbs, TEP diagnosed by imaging technique, acute clinic signs. Exclusion criteria: previous known neoplasia, non-idiopathic DVT, impossibility of follow-up. Results: The statistical analysis was performed on the basis of 122 patients out of 199 initially included, with an average follow-up of 38 months. At the end of the study no significant differences were found as regards the subsequent finding of a neoplasia in patients with positive TM values compared with those with negative values (Ca 125: P=0.161; Ca 15.3: P=0.930; CEA: P=0.703; PSA: P=0.382; AFP: 100% patients with negative values). Exempting the Ca 19.9 (P<0.000). Conclusions: As a conclusion of our study, TM as extensive screening of early stages of cancer after TED, is not useful for detecting an occult neoplasia during follow-up (AU)

Metástasis pancreática y tiroidea detectadas con 18F-FDG PET/TAC en paciente con cáncer colorrectal / Pancreatic and thyroid metastases detected with 18F-FDG PET/CT in patient with colorectal cancer

Mujer de 53 años diagnosticada de cáncer colorrectal, quien recibió tratamiento quirúrgico y quimioterápico, tras 5 años de remisión completa presenta una evolución atípica de su patología oncológica. La utilidad de la PET/TAC con 18F-FDG ha sido fundamental para la detección de las recidivas, sospechadas y no sospechadas, y para la monitorización de la respuesta al tratamiento(AU)

A 53-year-old woman with diagnosis of colorectal cancer, who received surgical treatment and chemotherapy. After 5-years of complete remission, she showed an atypical oncological evolution. The utility of 18F-FDG PET/CT scan has been fundamental to detect suspected and unsuspected recurrence and to monitor response to treatment(AU)

Telomeric repeat factor 1 protein levels correlates with telomere length in colorectal cancer / Los niveles proteicos del factor de repetición telomérico 1 se correlacionan con la longitud del telómero en el cáncer colorrectal

Background: colorectal cancer is the third cancer cause of death in Spain. It is important to investigate new tumoral markers for early diagnosis, disease monitoring and prevention strategies. Telomeres protect the chromosome from degradation by nucleases and endto- end fusion. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1) is a protein that binds at telomere ends. Purpose: to measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa. Method: from normal and tumoral samples of 83 patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration by Western Blot, telomerase activity, by the fluorescent- telomeric repeat amplification protocol assay and telomere length by Southern Blot. Results: high levels of TRF1 were observed in 68.7% of tumor samples, while the majority of normal samples (59%) showed negative or weak TRF1 concentrations. Among the tumor samples, telomere length was significantly associated with TRF1 protein levels (p = 0.023). Conclusions: a relationship was found between telomere length and TRF1 abundance protein in tumor samples, which means that TRF1 is an important factor in the tumor progression and maybe a diagnostic factor(AU)

Marcadores moleculares como factores predictivos de fracaso bioquímico en el cáncer de próstata después de tratamiento radical / Molecular markers as predictive factors biochemical failure after radical treatment of prostate cancer

En la actualidad, los nomogramas basados en los factores pronósticos "convencionales", como el grado de Gleason, el estadio tumoral y el PSA al diagnóstico, siguen siendo las mejores herramientas para predecir el pronóstico del cáncer de próstata (CP). Sin embargo, en la última década, se ha producido un notable avance biotecnológico que ha supuesto una fuente esencial para la investigación de nuevos marcadores moleculares de valor pronóstico y predictivo, tanto en tejido como en suero. En esta revisión, se repasarán los principales biomarcadores, tanto convencionales como más noveles, con principal atención a aquellos implicados en la respuesta a los tratamientos (radioterapia, cirugía u hormonoterapia). Aunque todavía no están preparados para su empleo rutinario en la practica clínica, la combinación de estos biomarcadores, con los marcadores tradicionales y las variables terapéuticas, nos permitirá seleccionar a los pacientes para ensayos con nuevas terapias dirigidas que en un futuro no muy lejano sean la base del tratamiento individualizado(AU)

Clinical nomograms based on Gleason grade, tumor stage, and serum PSA are still the best predictors of prostate cancer (PC) outcome. The biotechnological advancements achieved in the last decade represent a remarkable source for new prognostic and predictive tissue and serum molecular biomarkers. In this review, we will summarize conventional PC prognostic biomarkers and focus on novel identified biomarkers for PC early diagnosis and progression that might be used in the future. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pre-treatment and treatment-related variables and will improve our ability to predict outcome and select the optimal treatment(AU)