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Resumen Introduccion La quimioterapia adyuvante reduce significativamente las recidivas en el cancer de colon pN+ (estadio III) y en algunos pN0 (estadio II) con factores de riesgo (pT4, infiltracion vascular V1, infiltracion perineural Pn1, tumores complicados). Sin embargo, de manera no esperada, un 20-30% de los pN0 presentan recidivas en el seguimiento, lo que hace pensar que es posible que haya afectacion ganglionar que haya quedado oculta tras el estudio convencional histologico (EC), y su identificacion mediante un superestudio (SE) podria aumentar el numero de pacientes que se beneficiarian de quimioterapia adyuvante. No es posible hacer este superestudio de todos los ganglios linfaticos (GL) aislados en la linfadenectomia, pero si seria factible en un pequeno grupo de GL que fueran representativos del estatus N global (concepto de ganglio centinela [GC]). El objetivo de nuestro trabajo es determinar esa representatividad del GC y analizar el numero de pacientes que se supraestadifican tras el SE del GC. Material y metodos Estudio prospectivo en una serie de pacientes operados por cancer de colon con intencion curativa, a los que se les realiza biopsia selectiva de GC. La identificacion del GC se realizo mediante la inyeccion in vivo del radiotrazador, con aislamiento posterior ex vivo del GC. Tras la extraccion de la pieza se toman imagenes del lecho quirurgico para descartar vias aberrantes de drenaje linfatico fuera del area de reseccion oncologica habitual. Se realizo el EC histologico (tincion con hematoxilina-eosina con secciones convencionales) del resto de GL aislados del mesocolon. En el GC se realizo el EC y ademas un SE mediante hematoxilina-eosina en cortes seriados, inmunohistoquimica y estudio molecular con la tecnica One Step Nucleic Acid Amplification (OSNA®). Se efectuo un estudio de validez diagnostica de la biopsia selectiva de GC definiendo como falso negativo (FN) a la existencia de un GC negativo en presencia de otros GL afectados (N+), asi como una valoracion de la supraestadificacion conseguida gracias al SE del GC. Resultados Se realizo mapeo linfatico en 71 pacientes, detectandose el GC en 62 de los 71 pacientes (87,3%). Los 9 fallos de identificacion se concentran en los primeros 17 casos. No hemos encontrado pacientes con drenaje linfatico aberrante. Se estudian un total 1.164 GL en los 62 pacientes (18,8 GL/paciente), de los que 145 son GC (2,34 GC/paciente), encontrandose 103 GL positivos con el EC y 112 positivos con el SE del GC (9 GL+ mas en 8 pacientes que los detectados en el EC). La positividad tras el SE en el grupo GC es del 17,24% (25/145) mientras en el resto es del 8,53% (87/1.019) (p Conclusion La tecnica es valida y reproducible, con alta tasa de deteccion aunque con una clara curva de aprendizaje. Globalmente aumenta el numero de GL afectados en un 12,9% de los pacientes, con implicaciones pronosticas en un 4,8% (tasa de supraestadificacion). Solo un 3,2% de los pacientes pN0 en el EC pasan a ser pN+ tras el SE del GC, con la correspondiente consecuencia terapeutica (indicacion de quimioterapia adyuvante), hallazgo que seria relevante si se extrapola a un gran numero de pacientes. La alta tasa de FN (37,5%) impide asumir la representatividad de GC como indice del estatus pN global, pero esto no es trascendente en el CCR ya que su finalidad no es evitar la linfadenectomia, que sigue siendo obligatoria, (al reves que en cancer de mama o melanoma en los que la deteccion del GC si se usa para decidir sobre si se realiza o no la linfadenectomia), sino rescatar casos que pueden beneficiarse de quimioterapia adyuvante.

Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer (CC) and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20%-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN.Prospective study of a series of patients who have undergone curative surgery for CC, to whom we perform selective biopsy of sentinel node (SBDN). Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (Hematoxilin-Eosin stain (H-E) in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with H-E in serial sections, immunohistochemistry (IHC) and molecular study with OSNA® (One Step Nucleic Acid Amplification). Diagnostic validity study od SBSN was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN.We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/patient), from which 145 are SN (2,34 SN/patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9+ LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (P .001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a.Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in CC, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.