Diagnóstico y tratamiento de los quistes hepáticos. Utilidad de los marcadores tumorales intraquísticos (CEA y CA 19.9.) / Diagnosis and treatment of hepatic cysts: Usefulness of intracystic tumor markers (CEA and CA 19.9)

Introducción: El tratamiento de los quistes hepáticos requiere del diagnóstico diferencial de quiste simple hepático (QSH) de la neoplasia mucinosa quística (NMQ) hepática. Las características radiológicas no son patognomónicas. Algunos estudios han sugerido la utilidad de los marcadores tumorales (MKT) intraquísticos. Métodos: Análisis retrospectivo de base de datos prospectiva incluyendo pacientes diagnosticados de QSH sintomático desde el 2003 hasta el 2021. El objetivo del estudio es evaluar los resultados del tratamiento de los QSH sintomáticos y analizar la utilidad de la determinación de «carcinoembryonic antigen» (CEA) y «carbohydrate antigen» CA 19.9 intraquísticos. Resultados: Se incluyeron 50 pacientes tratados por quiste sintomático. En 15 pacientes el primer tratamiento fue el drenaje percutáneo. En 35 pacientes se realizó fenestración laparoscópica. Cuatro pacientes se diagnosticaron de lesiones premalignas/malignas (NMQ, NPIB, linfoma B); tres de ellos requirieron una segunda cirugía tras la fenestración y el diagnóstico anatomopatológico. La mediana de los valores de CEA y CA- 19.9 fue de 196μg/L y 227.321U/mL respectivamente. Los pacientes con lesiones premalignas no tuvieron valores elevados de MKT. El valor predictivo positivo fue del 0% en ambos MKT, y el valor predictivo negativo fue de 89% y 91% respectivamente. Conclusiones: Los valores de CEA y CA 19.9 intraquísticos no permiten distinguir los QSH de las NMH. El tratamiento más resolutivo de los QSH sintomáticos es la fenestración quirúrgica. El análisis anatomopatológico de la pared del quiste posibilita su correcto diagnóstico, permitiendo indicar una reintervención quirúrgica en los casos de NMQ.(AU)

Introduction: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not pathognomonic. Some studies have suggested the utility of intracystic tumor markers. Methods: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic “carcinoembryonic antigen” (CEA) and “carbohydrate antigen” CA 19.9. Results: Fifty patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, and lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19.9 were 196μg/L and 227.321U/mL, respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91%, respectively. Conclusion: Values of intracystic tumor markers CEA and CA 19.9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia.(AU)

[Clinical use and evolution of circulating biomarkers in the era of personalized oncology: From protein markers to bioclinical scores]. / Utilisation clinique et évolution des biomarqueurs circulants à l'ère de l'oncologie personnalisée : des marqueurs protéiques aux scores clinicobiologiques.

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria.

Value of preoperative HE4 as predictor of advanced disease in endometrioid endometrial cancer.

OBJECTIVE: To explore the predictive value of serum human epididymis protein 4 (HE4) marker in the preoperative prediction of the risk of advanced disease in the endometrioid subtype of endometrial cancer, and its association with poor prognostic factors. In addition, a cut-off value of HE4 was defined to classify patients according to these results. METHODS: Prospective and multicenter cohort analytical pilot study of patients operated for endometrial cancer at the Miguel Servet University Hospital of Zaragoza (Spain) and the Complejo Universitario of León (Spain) from January 2017 to May 2019. Preoperative serum levels of HE4 were analyzed by clinical and pathologic characteristics. RESULTS: In all, 126 patients were included. A statistically significant association was found between the preoperative HE4 value and node involvement (P = 0.008), late-stage disease (P = 0.003), high histologic grade (P = 0.007), deep myometrial invasion (P = 0.001), lymphovascular space invasion (P = 0.001), and other pathologic factors. In addition, an HE4 cut-off value (156.4 pmol/L) has been determined to predict, preoperatively, which patients will present with early stage disease. CONCLUSIONS: The preoperative marker HE4 is a useful tool in the preoperative study of patients with endometrial cancer as it relates to late-stage disease as well as other prognostic factors in the endometrioid subtype of endometrial cancer.

Carcinoma neuroendocrino de mama con diferenciación pulmonar. Reporte de un caso / Neuroendocrine breast carcinoma with pulmonary differentiation. A case report

Resumen ANTECEDENTES: Los carcinomas neuroendocrinos de mama son neoplasias malignas poco frecuentes, con incidencia de 2%. El diagnóstico es difícil de establecer debido a sus características clínicas y morfológicas inespecíficas. La inmunohistoquímica es un estudio útil para identificar marcadores neuroendocrinos. Es importante descartar los casos de metástasis relacionados con algún origen primario distinto, para de esta forma prescribir el tratamiento adecuado. CASO CLÍNICO: Paciente de 37 años, procedente de otra institución con diagnóstico sugerente de carcinoma de alto grado de células medianas, con diferenciación neuroendocrina, afectación de los tres niveles de Berg y adenopatías supraclaviculares patológicas. Después de los estudios de imagen y determinación de marcadores tumorales específicos de la enfermedad se estableció el diagnóstico de carcinoma neuroendocrino de mama. Se indicó tratamiento neoadyuvante con cisplastino y etoposido, con el que se observó reacción parcial de 50%. Posteriormente se efectuó la mastectomía radical, con vaciamiento de los tres niveles de Berg y extirpación de los ganglios supraclaviculares, sin complicaciones aparentes. En la actualidad, la paciente permanece estable, en tratamiento con quimioterapia coadyuvante. CONCLUSIÓN: Lo importante en estos casos es determinar los marcadores tumorales asociados con los carcinomas neuroendocrinos de mama y así poder establecer el diagnóstico certero e implementar el tratamiento adecuado, que puede variar en función de su origen. Hasta la fecha no existe un consenso de tratamiento, por lo que cada caso debe individualizarse. Se requieren estudios adicionales para ampliar el conocimiento de esta variante tumoral.

Abstract BACKDROUND: Neuroendocrine carcinomas are infrequent breast neoplasms representing less than 2% of breast neoplasms. The diagnosis is difficult, since their clinical and morphological characteristics do not help to differentiate them from other types of breast neoplasms. The immunohistochemistry that will determine the characterization of the tumor by the presence of neuroendocrine markers. It is important to rule out a cases of metastasis related to a different primary origin, in order to prescribe the appropriate treatment for the patient. CLINICAL CASE: A 37-year-old patient from another institution with a diagnosis suggestive of high-grade carcinoma of medium cells, with neuroendocrine differentiation, involvement of the 3 levels of Berg and pathological supraclavicular adenopathies. After performing the imaging studies and determining the specific tumor markers of the disease, the diagnosis of breast neuroendocrine carcinoma. Neoadjuvant treatment with cisplastin and etoposide is indicated, with the same partial reaction of 50%. Subsequently, the radical mastectomy was performed, with the emptying of the 3 levels of Berg and the removal of the supraclavicular nodes without apparent complications. Currently remains stable in the treatment with adjuvant chemotherapy. CONCLUSIONS: It is important to determine the tumor markers associated with breast neuroendocrine carcinomas, with the aim of establishing accurate diagnosis and implementing the appropriate treatment, which may vary depending on its origin. To date there is no consensus of treatment, so each case must be individualized. Additional studies are required to expand the knowledge of this tumor variant.

Antígenos asociados a tumores y su potencial uso en el tratamiento del cáncer / Tumor associated antigens and its potential use in cancer therapy

De acuerdo con cifras de la Organización Mundial de la Salud (OMS) en su reporte mundial de cáncer 2008, la incidencia de esta enfermedad se duplicó en las últimas tres décadas del siglo XX, y a pesar de los importantes esfuerzos de la ciencia por combatir este flagelo y de la creación de nuevas estrategias terapéuticas, se calcula que para 2050 la mitad de la población estará en riesgo de desarrollar algún tipo de cáncer. El rápido desarrollo de la tecnología en las últimas décadas ha permitido dilucidar algunos de los mecanismos moleculares y de las interacciones de la célula tumoral con el sistema inmunológico, que conllevan finalmente al desarrollo o eliminación del tumor y en los que la estructura antigénica de este juega un papel fundamental. El descubrimiento de una gran variedad de antígenos asociados a tumores ha permitido el desarrollo de inmunoterapias que mediante el uso de anticuerpos monoclonales o de vacunas para inmunización activa se han convertido en una nueva estrategia con interesantes y alentadoras perspectivas en el tratamiento de esta enfermedad. En este artículo se describen las características básicas de algunos de estos antígenos, su influencia en el desarrollo tumoral y su actual aplicación en inmunoterapias, con el fin de generar en el lector interés y expectativas acerca de este promisorio futuro terapéutico contra el cáncer.

According to the World Health Organization data in the World Cancer Report 2008, the cancer incidence was duplicated in the last three decades of the 20th century and in spite of the important efforts of the science for attacking this scourge and of the creation of new therapeutic strategies, it is calculated that for the year 2050, the half of the population will be in risk of developing some cancer type. The rapid development of the technology in the last decades has allowed explaining some of the molecular mechanisms and the interactions of the tumor cell with the immune system, that finally produces the tumor development or elimination and on the tumor antigenic structure plays a fundamental role. The discovery of variety of tumors associated antigens has allowed the immunotherapy development with the use of monoclonal antibodies or vaccines for active immunization, these news strategies represent important trends in cancer treatment. In this paper there are described some of these antigens in its basic characteristics, influence in the tumor development and current application in immunotherapy, in order to generate in the reader expectations about this future cancer therapy.

Tumoral markers in tumors of the pineal region.

In cases of pineal tumors, a germ cell tumor should always be suspected. As some of them are secreting tumors, tumoral markers (AFP and/or hGC) are an important part of the diagnostic process. Their positivity either in the serum and/or in the cerebrospinal fluid may lead to an accurate diagnosis, avoiding a potentially dangerous surgical biopsy. Follow-up of tumoral markers is useful during and after treatment in order to monitor response to chemotherapy or a remission status.

Estudio comparativo de dos métodos para la cuantificación del antígeno carcinoembrionario / Comparative study of two methods for carcinoembryonic antigen quantification / Estudo comparativo de dois métodos para a quantificação do antígeno carcinoembrionário

El antígeno carcinoembrionario (CEA) es una glicoproteína ampliamente utilizada como complemento del diagnóstico, monitoreo de tratamiento y evolución del cáncer colorrectal. El objetivo del presente trabajo fue realizar un análisis comparativo entre dos métodos para la determinación de CEA: electroquimioluminiscencia y quimioluminiscencia, en muestras de suero de 57 pacientes con diagnóstico de cáncer, principalmente colorrectal. Cuando se analizaron los datos totales se obtuvo una elevada correlación (r=0,9135, p<0,00001). Al realizar un corte de los resultados tomando como límite el valor de 4 ng/mL se observó que las mayores discrepancias entre métodos estuvieron en los valores considerados dentro del rango normal (r=0,5716, p<0,0014, n=29). Por el contrario, en concentraciones mayores al límite de corte, la correlación fue elevada (r=0,9453, p<0,00001, n=28). Estos resultados sugieren que, a diferencia de lo descripto por los fabricantes, los valores de CEA obtenidos por ambos métodos son comparables. La menor correlación observada en concentraciones inferiores a 4 ng/mL no sería tan relevante debido a que estos niveles se consideran dentro del rango de normalidad y, por lo tanto, su importancia desde el punto de vista clínico es relativa. Sin embargo, debido a que pueden detectarse con baja frecuencia diferencias individuales (atribuidas probablemente a diferencias en los epitopes detectados por cada método), para los casos con fuerte presunción clínica y un valor de CEA incongruente, se sugiere repetir la determinación por medio de otra metodología.

The carcinoembryonic antigen (CEA) is a glycoprotein widely employed in colorectal cancer, mainly as evolutive marker and as measure of therapy's ef-ficacy. The goal of this work was to perform a comparative study between two analytical methods to measure serum CEA levels: electrochemiluminescence (ECL) and chemilumines-cence (CL) in serum samples of 57 patients with diagnosis of cancer, mainly colorectal. On the whole, an elevated correlation between ECL and CL (r=0.9135; p<0.00001) was obtained. When data was analyzed with a cut-off value of 4 ng/mL, the main discrepancy between methods occurred in the range of normal values (r=0.5716; p<0.0014; n=29). On the contrary, in concentrations higher than the cut-off, the cor-relation was very high (r=0.9453; p<0.00001; n=28). These results suggest that, in spite of the reports of manufacturers, the CEA values obtained by both methods are comparable. The lower correlation observed in values below 4 ng/mL would not be significant because those values are in the normal range and, for that reason, their clinical importance is minor. However, due to the individual differences that could be detected in some patients (probably resulting from the differences in epitopes detected by each method), in cases with strong clinical evidence without concordance with the CEA result, it could be necessary to repeat the determination using another methodology.

O antígeno carcinoembrionário (CEA) é uma glicoproteína amplamente usada como complemento do diagnóstico, monitoração de tratamento e evolução do câncer colorretal. O objetivo deste trabalho foi realizar uma análise comparativa entre dois métodos para a detecção do CEA: eletroquimioluminescência e quimio-luminescência em amostras de soro de 57 pacientes com diagnóstico de câncer, principalmente colorretal. Quando analisados os dados totais, houve uma correlação elevada (r=0,9135, p<0,00001). Quando realizado um corte dos resultados tomando como valor limite 4 ng/mL, observou-se que as maiores diferenças entre ambos os métodos estiveram nos valores considerados dentro da faixa dos valores normais (r=0,5716, p<0,0014, n=29). No entanto, nas concentrações superiores respeito do limite de corte, a correlação foi elevada (r=0,9453, p<0,00001, n=28). Estes resultados sugerem que, comparado com o descrito pelos fabricantes, os valores de CEA obtidos por ambos os métodos são comparáveis. A menor correlação observada nas concentrações inferiores a 4 ng/mL não seria tão relevante devido a que estes níveis consideram-se dentro da faixa de normalidade e, portanto, sua importância, do ponto de vista clínico, é relativa. Contudo, devido a que podem ser detectados com baixa frequência diferenças individuais (atribuídas provavelmente a diferenças nos epitopos detectados por cada método), para os casos com forte suspeita clínica e um valor de CEA incongruente, sugere-se repetir a determinação através de outra metodologia.

Estudio comparativo de dos métodos para la cuantificación del antígeno carcinoembrionario / Comparative study of two methods for carcinoembryonic antigen quantification / Estudo comparativo de dois métodos para a quantificaþÒo do antígeno carcinoembrionário

El antígeno carcinoembrionario (CEA) es una glicoproteína ampliamente utilizada como complemento del diagnóstico, monitoreo de tratamiento y evolución del cáncer colorrectal. El objetivo del presente trabajo fue realizar un análisis comparativo entre dos métodos para la determinación de CEA: electroquimioluminiscencia y quimioluminiscencia, en muestras de suero de 57 pacientes con diagnóstico de cáncer, principalmente colorrectal. Cuando se analizaron los datos totales se obtuvo una elevada correlación (r=0,9135, p<0,00001). Al realizar un corte de los resultados tomando como límite el valor de 4 ng/mL se observó que las mayores discrepancias entre métodos estuvieron en los valores considerados dentro del rango normal (r=0,5716, p<0,0014, n=29). Por el contrario, en concentraciones mayores al límite de corte, la correlación fue elevada (r=0,9453, p<0,00001, n=28). Estos resultados sugieren que, a diferencia de lo descripto por los fabricantes, los valores de CEA obtenidos por ambos métodos son comparables. La menor correlación observada en concentraciones inferiores a 4 ng/mL no sería tan relevante debido a que estos niveles se consideran dentro del rango de normalidad y, por lo tanto, su importancia desde el punto de vista clínico es relativa. Sin embargo, debido a que pueden detectarse con baja frecuencia diferencias individuales (atribuidas probablemente a diferencias en los epitopes detectados por cada método), para los casos con fuerte presunción clínica y un valor de CEA incongruente, se sugiere repetir la determinación por medio de otra metodología.(AU)

The carcinoembryonic antigen (CEA) is a glycoprotein widely employed in colorectal cancer, mainly as evolutive marker and as measure of therapys ef-ficacy. The goal of this work was to perform a comparative study between two analytical methods to measure serum CEA levels: electrochemiluminescence (ECL) and chemilumines-cence (CL) in serum samples of 57 patients with diagnosis of cancer, mainly colorectal. On the whole, an elevated correlation between ECL and CL (r=0.9135; p<0.00001) was obtained. When data was analyzed with a cut-off value of 4 ng/mL, the main discrepancy between methods occurred in the range of normal values (r=0.5716; p<0.0014; n=29). On the contrary, in concentrations higher than the cut-off, the cor-relation was very high (r=0.9453; p<0.00001; n=28). These results suggest that, in spite of the reports of manufacturers, the CEA values obtained by both methods are comparable. The lower correlation observed in values below 4 ng/mL would not be significant because those values are in the normal range and, for that reason, their clinical importance is minor. However, due to the individual differences that could be detected in some patients (probably resulting from the differences in epitopes detected by each method), in cases with strong clinical evidence without concordance with the CEA result, it could be necessary to repeat the determination using another methodology.(AU)

O antígeno carcinoembrionário (CEA) é uma glicoproteína amplamente usada como complemento do diagnóstico, monitoraþÒo de tratamento e evoluþÒo do cÔncer colorretal. O objetivo deste trabalho foi realizar uma análise comparativa entre dois métodos para a detecþÒo do CEA: eletroquimioluminescÛncia e quimio-luminescÛncia em amostras de soro de 57 pacientes com diagnóstico de cÔncer, principalmente colorretal. Quando analisados os dados totais, houve uma correlaþÒo elevada (r=0,9135, p<0,00001). Quando realizado um corte dos resultados tomando como valor limite 4 ng/mL, observou-se que as maiores diferenþas entre ambos os métodos estiveram nos valores considerados dentro da faixa dos valores normais (r=0,5716, p<0,0014, n=29). No entanto, nas concentraþ§es superiores respeito do limite de corte, a correlaþÒo foi elevada (r=0,9453, p<0,00001, n=28). Estes resultados sugerem que, comparado com o descrito pelos fabricantes, os valores de CEA obtidos por ambos os métodos sÒo comparáveis. A menor correlaþÒo observada nas concentraþ§es inferiores a 4 ng/mL nÒo seria tÒo relevante devido a que estes níveis consideram-se dentro da faixa de normalidade e, portanto, sua importÔncia, do ponto de vista clínico, é relativa. Contudo, devido a que podem ser detectados com baixa frequÛncia diferenþas individuais (atribuídas provavelmente a diferenþas nos epitopos detectados por cada método), para os casos com forte suspeita clínica e um valor de CEA incongruente, sugere-se repetir a determinaþÒo através de outra metodologia.(AU)

Transforming activities of Chlamydia pneumoniae in human mesothelial cells.

Knowledge in viral oncology has made considerable progress in the field of cancer fight. However, the role of bacteria as mediators of oncogenesis has not yet been elucidated. As cancer still is the leading cause of death in developed countries, understanding the long-term effects of bacteria has become of great importance as a possible means of cancer prevention. This study reports that Chlamydia pneumoniae infection induces transformation of human mesothelial cells. Mes1 cells infected with C. pneumoniae at a multiplicity of infection of 4 inclusion-forming units/cell showed many intracellular inclusion bodies. After a 7-day infection an increased proliferative activity was also observed. Real-time PCR analysis revealed a strong induction of calretinin, Wilms' tumour gene 1, osteopontin, matrix metalloproteinases-2, and membrane-type 1 metalloproteinases gene expression in Mes1 cell, infected for a longer period (14 days). The results were confirmed by western blot analysis. Zymography analysis showed that C. pneumoniae modulated the in-vitro secretion of MMP-2 in Mes1 cells both at 7 and 14 days. Cell invasion, as measured by matrigel-coated filter, increased after 7 and 14 days infection with C. pneumoniae, compared with uninfected Mes1 cells. The results of this study suggest that C. pneumoniae infection might support cellular transformation, thus increasing lung cancer risk.

[Pediatric germ cell tumours]. / Les tumeurs germinales de l'enfant.

Germ cell tumours include a group of highly heterogeneous tumours regarding to their clinical and histological appearance. Altogether, they represent 3% of cancers diagnosed in children and adolescent younger than 15 years. A bimodal age distribution is observed with a small peak during infancy and a larger peak after puberty. Non-seminomateous germ cell tumours are largely predominant as compared to seminomateous tumours, rarely seen before puberty. During infancy, sacrococcygeal locations predominate with either teratomas in neonates or yolk sac tumours in infants above three months. In adolescents, mixed germ cell tumours predominate with either gonadal, mediastinal or intracranial tumour. Surgical resection of the tumour is fundamental and must be carcinologic and conservative at the same time. Neoadjuvant chemotherapy may help to decrease the volume of the tumour making possible a delayed sparing surgery. Indeed, except for teratomas, these tumours are highly sensitive to chemotherapy, in particular to platinum salts. Prognosis is good even in metastatic diseases. This raises the question of a therapeutic de-escalation in an attempt to decrease long-term toxicity, in particular audiologic and renal impairment. On the opposite, recurrent or refractory diseases after chemotherapy carry a dismal prognosis and therapeutic strategies remain to be defined in such situations.

[Tumor markers in colorectal cancer]. / Marcadores tumorales en el cáncer colorrectal.

INTRODUCTION: In 2008, colorectal cancer represented the third most commonly diagnosed tumor in Spain, and the second tumor with more deaths. Despite the new potential biomarkers in colorectal cancer, there are many challenges that need to be overcome, resulting in a need for the standardization of its determinations. DISCUSSION: The continuous advance in tumor disease knowledge makes this review a summary of the current accepted, recommended and studied tumor markers for the diagnosis and monitoring of colorectal cancer, such as fecal markers, tissue markers and serological markers, and various prognostic markers on which there are different lines of treatment in colorectal cancer. CONCLUSIONS: Oncological guidelines recommend only a minority of tumor markers for routine use, such as the study of fecal occult blood, CEA determination in the postoperative followup, microsatellite instability to identify people susceptible to hereditary nonpolyposis colorectal cáncer, and mutation of APC in the diagnosis of familial adenomatous polyposis.