P. Mathevet

The Sentinel Node Technique Detects Unexpected Drainage Pathways and Allows Nodal Ultrastaging in Early Cervical Cancer: Insights from the Multicenter Prospective SENTICOL Study

BackgroundSentinel lymph node (SLN) biopsy may improve nodal staging in cervical cancer. The aims of this study are to determine the rate of unusual patterns of cervical lymphatic drainage, to determine the rates of micrometastases and isolated tumor cells (ITCs) in SLNs, and to assess the clinical impact of SLN biopsy.MethodsMulticenter prospective study conducted between January 2005 and June 2007 in women undergoing laparoscopic surgery for early cervical cancer. Combined technetium/Patent Blue labeling was used. Lymphoscintigraphy was performed before surgery. SLN location was recorded, and factors associated with location were explored. SLNs underwent step sectioningxa0±xa0immunohistochemistry.Results145 patients were enrolled and 139 included in a modified intention-to-diagnose analysis. Although 80.6xa0% of SLNs were in external iliac and interiliac areas, 38.2xa0% of patients had at least one SLN in an unexpected area and 5.1xa0% had SLNs only in unexpected areas. In unexpected areas, the number of SLNs per patient was not significantly different between lymphoscintigraphy and intraoperative detection (0.79 [0.62–1.02] versus 0.50 [0.37–0.68]; Pxa0=xa00.096). In expected locations, there were significantly more blue and hot SLNs per patient than blue or hot SLNs (1.70 [1.45–1.99], 0.42 [0.30–0.57], 0.52 [0.39–0.69]). Of 28 metastatic SLNs, 17 contained micrometastases or ITCs. SLN involvement was found only by immunohistochemistry in 39.1xa0% of patients with positive nodes, and involved SLNs were located in unexpected areas in 17xa0% of those patients.ConclusionsSentinel lymph node biopsy detects unusual drainage pathways and micrometastases in a substantial proportion of patients, thus improving nodal staging.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort

PURPOSEnTo evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancernnnMETHODSnWe conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection. Sentinel lymph nodes (SLNs) were electively sampled before routine bilateral pelvic lymphadenectomy by laparoscopy.nnnRESULTSnOf 139 patients in the modified intention-to-diagnose analysis, 114 had centrally reviewed lymphoscintigrams, which showed 352 SLNs in 100 patients. Lymphoscintigraphy and ILM detection rates were 87.8% and 97.8%, respectively. Agreement between lymphoscintigraphy and ILM was low for the number of SLNs (κ=0.23; -0.04; 0.49) and bilateral SLNs (κ=0.36; 0.2; 0.52). No patient without SLNs by ILM had SLNs by lymphoscintigraphy. Lymphoscintigraphy identified substantial proportions of unusual drainage pathways. No patients with metastatic nodes had SLNs by lymphoscintigraphy but not by ILM in the relevant territory. In 1 of the 2 patients with false-negative SLN results, SLNs were bilateral by lymphoscintigraphy and unilateral by ILM.nnnCONCLUSIONnAlthough the detection rate was lower by lymphoscintigraphy than by ILM, the substantial proportions of SLNs in unusual territories provided valuable guidance for the surgical exploration. Awareness of the limited agreement between lymphoscintigraphic and surgical detection might help surgeons decrease the false-negative rate.

Feasibility and performance of lymphoscintigraphy in sentinel lymph node biopsy for early cervical cancer: results of the prospective multicenter SENTICOL study

ObjectiveTo evaluate feasibility, SLN detection rate, and SLN location of lymphoscintigraphy in sentinel lymph node (SLN) biopsy for early cervical cancer.MethodsAncillary analysis of data from the multicenter prospective SENTICOL study (January 2005–June 2007) of patients with early cervical cancer (FIGO stage IA with emboli to IB1) was conducted. Preoperative lymphoscintigraphy was performed after intracervical administration of 60 or 120xa0MBq of 99mTc-labeled radiocolloid on the day before (long protocol) or morning of (short protocol) surgery. SLNs were identified intraoperatively using combined radioactivity/patent blue detection. SLNs were sampled electively and routine bilateral pelvic lymphadenectomy was performed by laparoscopy. A centralized review of lymphoscintigraphies was performed to assess feasibility, detection rates, and anatomic SLN location.ResultsOf 139 patients included in the SENTICOL study, 133 received radiocolloid injection, and 131 (98.5xa0%) underwent preoperative lymphoscintigraphy, with the long protocol in three-fourths of cases. The lymphoscintigraphic detection rate was 87.8xa0%, with a median of 2 (1–4) SLNs per patient. By multivariate analysis, factors independently associated with lymphoscintigraphic SLN detection were age [odds ratio (OR) 0.91, 95xa0% confidence interval (95xa0% CI) 0.87–0.96; Pxa0<xa00.001], and protocol (long vs. short; OR 8.23, 95xa0% CI 1.87–36.25; Pxa0=xa00.005). Bilateral SLN identification by lymphoscintigraphy occurred in 67xa0% of cases and was independently influenced by age (OR 0.95, 95xa0% CI 0.92–0.98, Pxa0<xa00.001) and protocol (OR 5.42, 95xa0% CI 2.21–13.27; Pxa0<xa00.001). Although 60.5xa0% of preoperative SLNs were in the external iliac territory, unusual drainage patterns included the common iliac (19.6xa0%), para-aortic (10.8xa0%), and parametrial (6xa0%) basins.ConclusionsOur study demonstrates the feasibility and good detection rate of preoperative lymphoscintigraphy, with better detection in younger patients and with the long protocol. The high proportion of SLN basins in unexpected territories is of interest to guide intraoperative detection. Further studies are needed to better evaluate preoperative detection and to assess the contribution of lymphoscintigraphy to intraoperative detection.

Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study

AbstractBackgroundnThis study was designed to evaluate detection rate and anatomical location of sentinel lymph node (SLN) at lymphoscintigraphy, to compare short and long lymphoscintigraphy protocols, and to correlate lymphoscintigraphic and surgical mapping of SLN in patients with early-stage endometrial cancer (EC).MethodsnSubanalysis of the prospective multicenter study Senti-endo performed from July 2007 to August 2009. Patients with stage I and II EC received four cervical injections of 0–2xa0mL of unfiltered technetium sulphur colloid the day before (long protocol) or the morning (short protocol) before surgery. SLN detection used a combined technetium/patent blue labeling technique, and all patients had a systematic bilateral pelvic lymphadenectomy.nResultsA total of 133 patients were enrolled in the study and 118 (94.5xa0%) underwent a lymphoscintigraphy. Of these 118 patients, 44 (37xa0%) underwent a short protocol and 66 (56xa0%) a long protocol (data on lymphoscintigraphy were not available in eight patients). Lymphoscintigraphic detection rate was 74.6xa0% (34xa0% for short protocol and 60.2xa0% for long protocol). No difference in the detection rate was observed according to lymphoscintigraphy protocol (pxa0=xa00.22), but a higher number of SLN was noted for the long protocol (pxa0=xa00.02). Aberrant drainage was noted on lymphoscintigraphy in 30.5xa0% of the patients. Paraaortic SLNs were exclusively detected using the long protocol. A poor correlation was noted between short (κ testxa0=xa00.24) or long lymphoscintigraphy (κ testxa0=xa00.3) protocol and SLN surgical mapping.ConclusionsOur study demonstrates that preoperative lymphoscintigraphy allowed a high SLN detection rate and that long lymphoscintigraphy protocol was associated with a higher detection of aberrant drainage especially in the paraaortic area.

Response to Rossi et al. (Gynecol Oncol. 2012; 124(1):78–82)

We read with great interest the article by Rossi et al. entitled “Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: A feasibility study”, published in Gynecol Oncol [1]. This paper aimed at describing the feasibility of a new Sentinel LymphNode (SLN) technique using fluorescence imagingwith robotic assistance in stage 1 uterine cancer. The main objective of this study was to determine the dose of Indocyanine Green (ICG) required to detect at least one SLN in 80% of patients. Sixteen endometrial cancers and 4 cervical cancers were included in the study and had intracervical ICG injection. The detection rate was 85% (88% with 1 mg dose of ICG), with bilateral detection in 60% of cases. Of 3 patients with no SLN detection, one had a stage IIIC endometrial cancer, one had a metastatic serous fallopian tube cancer to the cervix and the third had a grade 1 stage IA endometrial cancer. Three patients had nodal involvement while 1 of these 3 was a false negative case of the SLN technique used (with ICG): a patient with unilateral SN detection and contralateral positive non SLN, and a second one with a detection failure (no SLN detected), leaving only one of the 3 cases where the SLN technique detected the positive nodes. We would like to congratulate the authors for this first description of robotic SLN procedure using fluorescence mapping. Nevertheless, we have a few concerns that we would like to share with the authors. First of all, this is a small series including endometrial and cervical cancers. The route of injection is controversial in endometrial cancer whereas the intracervical one is the reference in cervical cancer [2]. The authors should not havemixed these two tumor sites as lymphatic drainage pathways are probably different. Moreover mixed mullerian tumors have been included which is not a common indication of the SLN procedure. We are concerned by a few technical points. First, the dosage study appears a little bit limited as only 3 patients were explored with different doses and the 17 remaining patients had a single dosage. Furthermore, we have no information on SLNs ultrastaging. One major concern is the really low detection and bilateral detection rates compared to the combined technique, which might be related to the tracer uptake. The authors report a poor sensitivity and a false negative case with unilateral detection. Their results in terms of detection and false negative rates are less good than the ones described with the combined technique [3,4]. One explanation is that the fluorescent dye used is not clearly representative of the lymphatic drainage and/or that the nodal uptake is not efficient for easy detection of the first potentially involved lymph node. At last, no information on the learning curve is available and we do consider that this promising novel technique may be difficult to master due to the lack of a robotically assisted fluorescence device. To conclude, high detection rate and low false negative rate are required to validate the SLN technique. The isotopic and colored technique has broadly proved its validity. In order to evaluate other alternative techniques of SLN detection, a comparison with the combined procedure is required and advantages of the new techniques should be presented. So further studies are needed to assess this new fluorescence mapping technique in targeted indications and with larger populations of patients. Anne-Sophie Bats, MD, PhD Patrice Mathevet, MD, PhD Fabrice Lécuru, MD, PhD

Tecnica e risultati del prelievo del linfonodo sentinella nei cancri del collo e del corpo dell’utero

La biopsia del linfonodo sentinella e una metodica diagnostica che permette il prelievo linfonodale mirato delle prime stazioni linfonodali di un tumore, rappresentativo dei linfonodi a valle. Questa tecnica si sviluppa da una decina di anni nei cancri dell’utero, per i quali lo status linfonodale e un fattore prognostico principale. I suoi obiettivi principali sono di ridurre la morbilita degli svuotamenti completi, di individuare dei territori di drenaggio inattesi e, anche, di realizzare un’ultrastadiazione linfonodale. La tecnica di rilevamento combinata, con coloranti e isotopi, e quella che apporta i migliori risultati in termini di tasso di individuazione. I dati della letteratura sulla biopsia del linfonodo sentinella nei cancri del collo precoci hanno dimostrato ampiamente la sua fattibilita. I tassi di individuazione sono molto buoni, come anche il suo valore diagnostico. La tecnica permette di realizzare un’ultrastadiazione linfonodale evidenziando delle micrometastasi. Il prelievo del linfonodo sentinella e realizzabile anche nei cancri dell’endometrio, con, tuttavia, dei tassi di individuazione e di falsi negativi molto variabili secondo le casistiche, influenzati soprattutto dalla via di iniezione. Se l’iniezione intratumorale, realizzata soprattutto mediante isteroscopia, e quella che permette di evidenziare meglio il vero drenaggio linfatico del tumore, la sua attuazione e, tuttavia, assai poco riproducibile.

Técnica y resultados de la biopsia del ganglio centinela en los cánceres del cuello y del cuerpo uterinos

La biopsia del ganglio centinela es un metodo diagnostico que permite la extirpacion dirigida de las primeras invasiones ganglionares de un tumor, una muestra que es representativa de los ganglios subsiguientes. Esta tecnica se esta desarrollando desde hace unos 10 anos con relacion a los canceres del utero, en los cuales el estado ganglionar es un factor pronostico principal. Sus objetivos principales son limitar la morbilidad de los vaciamientos ganglionares completos, detectar territorios de drenaje inesperados y efectuar una ultraestadificacion ganglionar. La tecnica de deteccion combinada, por tincion e isotopica, produce los mejores resultados en cuanto a indices de deteccion. Los datos de las publicaciones sobre la biopsia precoz del ganglio centinela en los canceres del cuello uterino confirman ampliamente la utilidad de esta practica. Los indices de deteccion y el valor diagnostico son muy buenos. La tecnica hace posible una ultraestadificacion ganglionar para demostrar micrometastasis. La biopsia del ganglio centinela tambien es factible en los canceres de endometrio, pero los indices de deteccion y de falsos negativos varian mucho segun las series, principalmente en relacion con la via de inyeccion. Aunque la inyeccion intratumoral por histeroscopia es la que permite demostrar mejor el verdadero drenaje linfatico del tumor, su realizacion es bastante poco reproducible.