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3.
Dis Colon Rectum ; 64(11): 1354-1363, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34192710

RESUMEN

BACKGROUND: Lymph node metastasis is the single most important prognostic risk factor for recurrence in patients with colon cancer who have undergone curative surgery. The routine method for detecting disseminated tumor cells in lymph nodes is microscopic examination of one or a few hematoxylin and eosin-stained tissue sections by a trained pathologist. This method, however, is insensitive mainly because less than 1% of the lymph node volume is examined, leading to misclassification. OBJECTIVE: This study aimed to investigate whether analysis of a selected group of biomarker mRNAs improves detection and characterization of lymph node metastases/micrometastases compared with the routine method. DESIGN: This study is a side-by-side comparison of biomarker mRNA analysis and histopathology of 185 lymph nodes from patients with colon cancer representing stages I to IV, and an investigation of the importance of lymph node tissue volume for tumor cell detection. SETTINGS: This is a collaborative study between a high-volume central hospital and a preclinical university institution. PATIENTS: Fifty-seven patients who had undergone tumor resection for colon cancer were included. MAIN OUTCOME MEASURES: The primary outcomes measured were mRNA copies per 18S rRNA copy of CEACAM5, KLK6, SLC35D3, POSTN, and MUC2 by multiplex assay and metastases/micrometastases detected by histopathology. RESULTS: The number of tumor cell-positive lymph nodes was 1.33-fold higher based on CEACAM5 mRNA levels compared with histopathological examination. Increasing the tissue volume analyzed for CEACAM5 levels from an 80-µm section to half a lymph node increased the number of positive nodes from 34 of 107 to 80 of 107 (p < 0.0001). Similarly, the number of positive nodes for the aggressiveness marker KLK6 increased from 9 of 107 to 24 of 107. LIMITATIONS: Only a limited number of individual lymph nodes per patient was available for analysis. CONCLUSIONS: mRNA analysis of CEACAM5, KLK6, and SLC35D3 improves the detection of tumor cells in lymph nodes from patients surgically treated for colon cancer, and, together with POSTN and MUC2, it further allows characterization of the tumor cells with respect to aggressiveness and the tumor cell environment. See Video Abstract at http://links.lww.com/DCR/B650. EL ANLISIS DE ARNM DE CEACAM, KLK, SLCD, POSTN Y MUC MEJORA LA DETECCIN Y PERMITE LA CARACTERIZACIN DE CLULAS TUMORALES EN LOS GANGLIOS LINFTICOS DE PACIENTES CON CNCER DE COLON: ANTECEDENTES:Las metástasis en los ganglios linfáticos son el factor de riesgo pronóstico más importante de recurrencia en pacientes con cáncer de colon que se han sometido a cirugía curativa. El método de rutina para detectar células tumorales diseminadas en los ganglios linfáticos es el examen microscópico de una o algunas secciones de tejido teñidas con hematoxilina-eosina por un patólogo capacitado. Sin embargo, este método es insensible principalmente porque se examina menos del 1% del volumen de los ganglios linfáticos, lo que conduce a una clasificación errónea.OBJETIVO:Investigar si el análisis de un grupo seleccionado de ARNm de biomarcadores mejora la detección y caracterización de metástasis / micrometástasis en los ganglios linfáticos en comparación con el método de rutina.DISEÑO:Una comparación en paralelo del análisis de ARNm de biomarcadores y la histopatología de 185 ganglios linfáticos de pacientes con cáncer de colon que representan las etapas I-IV, e investigación de la importancia del volumen de tejido de los ganglios linfáticos para la detección de células tumorales.ENTORNO CLINICO:Estudio colaborativo entre un hospital central de alto volumen y una institución universitaria preclínica.PACIENTES:Cincuenta y siete pacientes que han sido sometidos a resección tumoral por cáncer de colon.PRINCIPALES MEDIDAS DE VALORACION:copias de ARNm / copia de ARNr 18S de CEACAM5, KLK6, SLC35D3, POSTN y MUC2 mediante análisis múltiple y metástasis / micrometástasis detectadas por histopatología.RESULTADOS:El número de ganglios linfáticos con células tumorales positivas fue 1,33 veces mayor según los niveles de ARNm de CEACAM5 en comparación con el examen histopatológico. El aumento del volumen de tejido analizado para los niveles de CEACAM5 de una sección de 80 µm a la mitad de un ganglio linfático aumentó el número de ganglios positivos de 34/107 a 80/107 (p <0,0001). De manera similar, el número de nodos positivos para el marcador de agresividad KLK6 aumentó de 9/107 a 24/107.LIMITACIONES:Solo un número limitado de ganglios linfáticos individuales / paciente estuvo disponible para el análisis.CONCLUSIONES:El análisis de ARNm de CEACAM5, KLK6 y SLC35D3 mejora la detección de células tumorales en los ganglios linfáticos de pacientes con cáncer de colon tratados quirúrgicamente y, junto con POSTN y MUC2, permite además la caracterización de las células tumorales con respecto a la agresividad y el entorno celular tumoral. Consulte Video Resumen en http://links.lww.com/DCR/B650.


Asunto(s)
Antígeno Carcinoembrionario/genética , Moléculas de Adhesión Celular/genética , Neoplasias del Colon/genética , Calicreínas/genética , Proteínas de Transporte de Monosacáridos/genética , Mucina 2/genética , Anciano , Anciano de 80 o más Años , Colectomía , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Femenino , Proteínas Ligadas a GPI/genética , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , ARN Mensajero/metabolismo
4.
Scand J Urol ; 55(3): 235-241, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33999764

RESUMEN

BACKGROUND: Transrectal prostate biopsy (TRbx) carries an increasing risk of infection. The Forsvall Needle Prototype (FNP) is a novel biopsy needle that reduces bacterial load brought across the rectum and may therefore reduce infection risk. The objective of this study was to compare biopsy length, quality and patient experience for the FNP Version 2 (FNP2) versus a standard Tru-Cut needle. METHODS: We conducted a randomized, parallel-group, non-inferiority trial with twenty consecutive patients eligible for TRbx. Participants were randomized to undergo TRbx using either FNP2 or a standard Tru-Cut needle. The primary outcome was difference in mean biopsy lengths measured by the pathologist. FNP2 biopsy lengths ≤1.35 mm of the standard needle length were considered non-inferior. Secondary outcomes were biopsy length in the needle chamber and immediately after removal, biopsy quality, biopsy fragmentation, patient discomfort/pain, and complications (immediate and after 14 and 30 days). RESULTS: Mean pathologist-measured FNP2 biopsy length was non-inferior compared to the standard Tru-Cut needle (0.02 mm longer, 95%CI-0.73 to 0.76 mm). Biopsy length in the needle chamber and immediately after removal were also non-inferior. Biopsy quality and patient discomfort were not significantly different for the FNP2 and the standard Tru-Cut needle. Biopsy fragmentation was more common in the FNP2 group. CONCLUSIONS: The FNP2 biopsy needle is non-inferior to the Tru-Cut needle in terms of biopsy length and not significantly different in terms of biopsy quality and patient experience. Future studies will evaluate the Forsvall needle design's effect on post-biopsy infection risk.


Asunto(s)
Biopsia con Aguja , Próstata , Recto , Biopsia , Humanos , Masculino , Evaluación del Resultado de la Atención al Paciente
5.
Virchows Arch ; 465(6): 649-59, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25326863

RESUMEN

Gastric cancer is the second most common cause of cancer-related death worldwide, and the incidence of esophageal adenocarcinoma is rising. While some progress has been made in treatment strategies, overall survival remains very poor for patients with adenocarcinoma in the upper gastrointestinal tract. Special AT-rich sequence binding protein 1 (SATB1) is a global genome organizer that has been demonstrated to promote aggressive tumor behavior in several different types of cancer, including gastric cancer. The prognostic value of SATB1 expression in esophageal cancer has, however, not yet been described. In this study, expression of SATB1 was examined by immunohistochemistry on tissue microarrays prepared from tissue samples from 175 patients with adenocarcinoma of the esophagus, cardia, or stomach and containing normal tissue, intestinal metaplasia, primary tumors, and metastases. A well-validated antibody was used. We found SATB1 to be an independent prognostic factor in patients with a radically resected tumor, correlating with shorter overall survival as well as with shorter recurrence-free survival. SATB1 expression was also found to be significantly lower in primary tumors associated with intestinal metaplasia than those without intestinal metaplasia. This observation is of potential biological interest as it has been proposed that intestinal metaplasia-associated tumors constitute a less aggressive phenotype.


Asunto(s)
Adenocarcinoma/patología , Neoplasias Esofágicas/patología , Proteínas de Unión a la Región de Fijación a la Matriz/biosíntesis , Neoplasias Gástricas/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Biomarcadores de Tumor/análisis , Western Blotting , Cardias/patología , Supervivencia sin Enfermedad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Proteínas de Unión a la Región de Fijación a la Matriz/análisis , Persona de Mediana Edad , Lesiones Precancerosas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Análisis de Matrices Tisulares
6.
Biomark Res ; 2: 11, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24963396

RESUMEN

BACKGROUND: High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma. MATERIAL AND METHODS: Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett's esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS). RESULTS: RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS). CONCLUSION: High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation.

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