Respuesta biológica en las pacientes con cáncer de mama tratadas con radioterapia intraoperatoria / Biological response in breast cancer patients using intraoperative radiotherapy

Introducción: el tratamiento conservador de la mama junto con la radioterapia es de elección en las pacientes con cáncer de mama precoz. Gracias a un mayor conocimiento de la radiobiología tumoral, la tendencia actual consiste en utilizar técnicas de irradiación parcial acelerada, entre las que destaca la radioterapia intraoperatoria (RIO). Métodos: estudio prospectivo multicéntrico dividido en 2 grupos comparativos con casos consecutivos de las pacientes a que han recibido una cirugía conservadora por cáncer de mama asociada o no a RIO. Se valora la relación de esta terapia con los valores de las proteínas involucradas en la respuesta biológica (IL6, IL8, CXCL10, IL1β y TNF- α) en muestras de suero preoperatorio y a las 24 h desde la cirugía, y de drenaje quirúrgico a las 6 y 24 h desde la cirugía. Resultados: se ha objetivado en las pacientes tratadas con RIO una disminución significativa de IL6 e IL8, así como un aumento de CXCL10 favorable para la lucha contra la progresión del tumor (p valor < 0,05). Las alteraciones del sistema inmunológico se manifiestan tanto en suero como en débito del drenaje quirúrgico a las 6 y 24 h desde la cirugía. Conclusiones: la RIO modifica la respuesta biológica en las pacientes con cáncer de mama. A pesar de que se deben desarrollar más líneas de investigación, la comprensión de los mecanismos de desarrollo del tumor, abre una nueva etapa en el desarrollo de tratamientos perioperatorios dirigidos a dianas concretas que compensen las consecuencias dañinas de la cirugía. (AU)

Introduction: Breast conserving surgery with radiotherapy is the treatment of choice in patients with early breast cancer. Due to a better understanding of tumour radiobiology, the current trend is to use accelerated partial irradiation techniques, among which intraoperative radiotherapy (RIO) stands out. Methods: Prospective multicentre study divided into two comparative groups with consecutive cases of patients who have undergone conservative surgery for breast cancer associated or not with RIO. The relation of this therapy with the values of proteins involved in the biological response (IL6, IL8, CXCL10, IL1β y TNF- α) is assessed in serum samples preoperative and 24 hours after surgery, and surgical drainage samples at 6 and 24 hours after surgery. Results: A significant decrease in IL6 and IL8, as well as an increase in CXCL10 favourable for the fight against tumour progression (p-value < 0.05) was observed in patients treated with RIO. Immune system alterations are manifested in both serum and surgical drainage debit at 6 and 24 hours after surgery. Conclusions: RIO modifies the biological response in breast cancer patients. Although more lines of research need to be developed, the understanding of the mechanisms of tumour development opens a new stage in the development of perioperative treatments directed at specific targets that compensate for the harmful consequences of surgery. (AU)

Cirugía conservadora de cáncer de mama y radioterapia intraoperatoria. ¿Podemos predecir la fibrosis? / Breast-conserving surgery in breast cancer and intraoperative radiotherapy. Can we predict the fibrosis?

Introducción: Las técnicas de radioterapia asociadas a la cirugía conservadora del cáncer de mama precoz han evolucionado gracias a un mayor conocimiento de la radiobiología tumoral, destacando entre ellas la radioterapia intraoperatoria (RIO). Sin embargo, se han documentado complicaciones con dicha técnica, principalmente la fibrosis. El factor de crecimiento transformante beta (TGF-β) es una citocina relacionada con la fibrosis inducida después de la radiación que podría servir como marcador temprano del riesgo de desarrollo de la misma. Métodos: Estudio prospectivo multicéntrico de 60 pacientes a las que se les ha sometido a cirugía conservadora por cáncer de mama, asociada a RIO en 30 de ellas. Se evalúan los valores de TGF-β en muestras de suero preoperatorio y a las 24 h desde la cirugía, y de muestras de drenaje a las 6 y 24 h desde la cirugía. Resultados: Los valores de TGF-β objetivados en el suero y en el débito de drenaje a las 24 h desde la cirugía de las pacientes que recibieron RIO fueron significativamente mayores que los de aquellas que no la recibieron (p < 0,0001). De entre ellas, 8 pacientes presentaron valores superiores a 1.000 pg/ml. Estas diferencias entre los grupos no se modifican por el tipo de muestra utilizada, bien sea suero, bien débito de drenaje (p = 0,5881). Conclusiones: Aunque deben realizarse más estudios, valores elevados de TGF-β en las pacientes con cáncer de mama a las que se les realiza cirugía conservadora asociada a RIO pueden predecir el riesgo de fibrosis

Introduction: Radiotherapy techniques associated with breast-conserving surgery have evolved in early breast cancer thanks to a better knowledge of tumor radiobiology, highlighting intraoperative radiotherapy (IORT). However, complications have been documented with this procedure, mainly fibrosis. Transforming growth factor beta (TGF-β) is a cytokine with an active role in radiation-induced fibrosis, which could be used as an early biomarker for the development of fibrosis. Methods: Multicentric prospective analysis of 60 patients with breast cancer who underwent breast-conserving surgery, 30 of whom had received additional IORT. TGF-β values were evaluated in serum pre-surgery and in serum collected 24 h after surgery. In addition, we evaluated surgical wound fluids collected 6 h and 24 h following surgery. Results: Serum and surgical wound fluids TGF-β values collected over 24 h following surgery were significantly higher in patients who received additional IORT (P < .0001). Notably, 8 of these patients showed values above 1,000 pg/ml. There were no differences between the samples (serum or surgical wound fluids) (P = .5881). Conclusions: Although further investigation is needed, higher TGF-β values in IORT during breast-conserving surgery can be used as an early biomarker for the development of fibrosis

Breast-conserving surgery in breast cancer and intraoperative radiotherapy. Can we predict the fibrosis? / Cirugía conservadora de cáncer de mama y radioterapia intraoperatoria. ¿Podemos predecir la fibrosis?

INTRODUCTION: Radiotherapy techniques associated with breast-conserving surgery have evolved in early breast cancer thanks to a better knowledge of tumor radiobiology, highlighting intraoperative radiotherapy (IORT). However, complications have been documented with this procedure, mainly fibrosis. Transforming growth factor beta (TGF-ß) is a cytokine with an active role in radiation-induced fibrosis, which could be used as an early biomarker for the development of fibrosis. METHODS: Multicentric prospective analysis of 60 patients with breast cancer who underwent breast-conserving surgery, 30 of whom had received additional IORT. TGF-ß values were evaluated in serum pre-surgery and in serum collected 24h after surgery. In addition, we evaluated surgical wound fluids collected 6h and 24h following surgery. RESULTS: Serum and surgical wound fluids TGF-ß values collected over 24h following surgery were significantly higher in patients who received additional IORT (P<.0001). Notably, 8 of these patients showed values above 1,000pg/ml. There were no differences between the samples (serum or surgical wound fluids) (P=.5881). CONCLUSIONS: Although further investigation is needed, higher TGF-ß values in IORT during breast-conserving surgery can be used as an early biomarker for the development of fibrosis.

Clinical, Anatomical, and Pathological Grading Score to Predict Technical Difficulty in Laparoscopic Splenectomy for Non-traumatic Diseases.

BACKGROUND: We aimed to develop a grading system based on preoperative parameters that would predict surgical difficulty and morbidity in elective laparoscopic splenectomy. STUDY DESIGN: We retrospectively assessed morbidity in 439 patients who underwent laparoscopic splenectomy for benign and malignant disorders between 1993 and 2013. Medical and surgical records were reviewed and analyzed. We compared preoperative data concerning demographic, clinical, pathological, anatomical, laboratory, and radiological factors with three surgical outcomes: operative time, intraoperative bleeding, and surgical conversion. Univariate and multivariate analyses were performed to identify statistically significant variables. A logistic regression model was used to identify determinant variables and to compose a predictive score. External validation of the score was performed using an independent cohort of 353 patients. RESULTS: Four preoperative parameters (age, male sex, type of pathology, and spleen size based on final spleen weight) were significantly related with operative time, operative bleeding, and conversion to open surgery. Using these results, we developed a classification system with three levels of difficulty: low (≤4 points), medium (4.5-5.5 points), and high (≥6 points), based on the four preoperative parameters. The correlation was highly significant (p = <0.001) according to Spearman's correlation. The area under the ROC curve was 0.671 (95 % CI 0.596-0.745). The external validation showed significant correlations with the present model. CONCLUSIONS: The grading score described here is simple to calculate from the physical examination, laboratory tests, and US or CT images, and we believe it could be useful to preoperatively assess the technical complexity of laparoscopic splenectomy.

El papel del ganglio centinela en la evolución del cáncer de colon / The role of sentinel lymph node in colon cancer evolution

INTRODUCCIÓN: El objetivo de este estudio es llevar a cabo la evaluación de la técnica de detección del ganglio centinela (GC) con tinción de azul de metileno «ex vivo» en el cáncer de colon, así como calcular la supraestadificación y su correlación con la evolución de la enfermedad. MÉTODOS: Entre 2008 y 2011, 101 pacientes fueron operados de cáncer de colon con la detección del GC, estudiándose las micrometástasis. El seguimiento de los pacientes N0 fue mayor a un año en búsqueda de recidivas y si tenían relación con la aparición de dichas micrometástasis. RESULTADOS: El índice de detección del GC fue de 92 casos (91%). Fue positivo para micrometástasis en 9 casos, con una supraestadificación del 14%. La incidencia de falsos negativos fue de 9 pacientes (10%). El seguimiento medio de los 74 pacientes N0 fue de 38 meses. Se observó recurrencia en 4 pacientes (7%) del grupo de pacientes con GC− (65 pacientes) y en 2 pacientes (22%) en el grupo con GC+ (9 pacientes, sin diferencias estadísticas significativas. Tampoco se observaron diferencias en términos de supervivencia entre los 2 grupos. CONCLUSIONES: El estudio del GC es una práctica reproducible sin aumento significativo del tiempo y de costes. Puede llegar a supraestadificar el 14% de pacientes que habían sido clasificados como N0 con técnica convencional. En el seguimiento de los pacientes N0 con GC+ parece haber una tendencia a un porcentaje mayor de recidivas, lo que podría llevar a cambios en las pautas de tratamiento adyuvante, aunque debemos tomarlo con cautela ya que la muestra es escasa

INTRODUCTION: The aim of this study is to evaluate the sentinel lymph node mapping (SLNM) with methylene blue staining "ex vivo" in colon cancer, as well as calculate the upstaging obtained by the determination of micrometastases and its correlation with the evolution of the disease. METHODS: Between 2008 and 2011, 101 patients with colon cancer undergoing resection were studied prospectively with SLNM and detection of micrometastases. The correlation of SLN micrometastases with the disease evolution was evaluated in patients with a follow-up of more than one year. RESULTS: The SLNM rate was 92 cases (91%). Only SLN was positive for micrometastases in 9 cases, with a 14% upstaging. The incidence of false negatives was 9 patients (10%). Mean follow of N0 patients (n = 74) was 38 months. The SLN- (negative) group (65 patients) had a recurrence rate of 4 patients (7%), whereas this rate was 2 patients (22%) in the group of SLN + (positive) (9 patients), but without significant differences. No differences in survival were observed. CONCLUSIONS: SLNM is a reproducible technique without significant increase in time and costs. Upstaging was obtained in 14% of patients staged as N0 by conventional technique. At follow-up of N0 patients with SLN + there seems to be a higher rate of recurrence, which could change the guidelines of adjuvant treatment, but we must interpret the results it with caution because the sample is small

The role of sentinel lymph node in colon cancer evolution.

INTRODUCTION: The aim of this study is to evaluate the sentinel lymph node mapping (SLNM) with methylene blue staining "ex vivo" in colon cancer, as well as calculate the upstaging obtained by the determination of micrometastases and its correlation with the evolution of the disease. METHODS: Between 2008 and 2011, 101 patients with colon cancer undergoing resection were studied prospectively with SLNM and detection of micrometastases. The correlation of SLN micrometastases with the disease evolution was evaluated in patients with a follow-up of more than one year. RESULTS: The SLNM rate was 92 cases (91%). Only SLN was positive for micrometastases in 9 cases, with a 14% upstaging. The incidence of false negatives was 9 patients (10%). Mean follow of N0 patients (n=74) was 38 months. The SLN- (negative) group (65 patients) had a recurrence rate of 4 patients (7%), whereas this rate was 2 patients (22%) in the group of SLN+(positive) (9 patients), but without significant differences. No differences in survival were observed. CONCLUSIONS: SLNM is a reproducible technique without significant increase in time and costs. Upstaging was obtained in 14% of patients staged as N0 by conventional technique. At follow-up of N0 patients with SLN+there seems to be a higher rate of recurrence, which could change the guidelines of adjuvant treatment, but we must interpret the results it with caution because the sample is small.