Rik Pijpers

Functional lymphatic anatomy for sentinel node biopsy in breast cancer: echoes from the past and the periareolar blue method.

OBJECTIVE To simplify and improve the technique of axillary sentinel node biopsy, based on a concept of functional lymphatic anatomy of the breast. SUMMARY BACKGROUND DATA Because of their common origin, the mammary gland and its skin envelope share the same lymph drainage pathways. The breast is essentially a single unit and has a specialized lymphatic system with preferential drainage, through select channels, to designated (sentinel) lymph nodes in the lower axilla. METHODS These hypotheses were studied by comparing axillary lymph node targeting after intraparenchymal peritumoral radiocolloid (detected by a gamma probe) with the visible staining after an intradermal blue dye injection, either over the primary tumor site (90 procedures) or in the periareolar area (130 procedures). The radioactive content, blue coloring, and histopathology of the individual lymph nodes harvested during each procedure were analyzed. RESULTS Radiolabeled axillary nodes were identified in 210 procedures, and these were colored blue in 200 cases (94%). The targeting concordance between peritumoral radiocolloid and intradermal blue dye was unrelated to the breast tumor location or the site of dye injection. Radioactive sentinel nodes were not stained blue in 10 procedures (5%), but this mismatching could be explained by technical problems in all cases. In two cases (1%), the (pathologic) sentinel node was blue but had no detectable radiocolloid uptake. CONCLUSIONS The lessons learned from this study provide a functional concept of the breast lymphatic system and its role in metastasis. Anatomical and clinical investigations from the past strongly support these views, as do recent sentinel node studies. Periareolar blue dye injection appears ideally suited to identify the principal (axillary) metastasis route in early breast cancer. Awareness of the targeting mechanism and inherent technical restrictions remain crucial to the ultimate success of sentinel node biopsy and may prevent disaster.

The sentinel lymph node status is an important factor for predicting clinical outcome in patients with Stage I or II cutaneous melanoma.

In a cohort of patients, the authors investigated whether and to what extent the sentinel lymph node (SLN) status contributes to predicting the probability of remaining disease free for at least 3 years. In addition, several traditional prognostic factors were analyzed: Breslow thickness, Clark invasion level, ulceration, lymphatic invasion, location, type of the melanoma, and age and gender of the patient.

The impact of dynamic lymphoscintigraphy and gamma probe guidance on sentinel node biopsy in melanoma

In cutaneous melanoma, biopsy of the first tumour-draining lymph node (sentinel node, SN) may replace routine elective lymph node dissection (ELND). Even in experienced hands the original technique using vital dyes fails to localise the SN in 20% of cases. In this study we investigated whether the procedure benefits from lymphoscintigraphy and the use of a gamma probe. In 41 patients technetium-99m-colloidal albumin was injected intracutaneously around the scar of the excised tumour. This was followed by dynamic and late static imaging. The first focal accumulation was assumed to be the SN. In all patients at least one SN was found, in 95% within the first 20 min. By showing multiple or ramifying lymphatic channels, dynamic lymphoscintigraphy differentiated between spill and multiple SNs. In all cases the initial focus retained the highest fraction of radioactivity for at least 18 h. The gamma probe was especially useful in the axilla and neck, where it accurately showed the optimal incision site and facilitated the search for deep-seated nodes. Gamma probe-localised SNs were dye-positive in 93% of cases. The SN contained metastases in 20% of the patients. Only in these patients was ELND performed, which revealed that the SN had been the only metastatic node in four of eight cases. We conclude that dynamic lymphoscintigraphy is essential for SN localisation, that tracer kinetics allow flexible timing of surgery, and that the surgical procedure benefits from use of the gamma probe.

Sentinel node detection in cervical cancer

Background For superficial tumors such as melanoma, breast, and vulvar cancer, sentinel node detection prevents unnecessary extensive lymph node dissections. Sentinel node detection has not yet proved feasible in tumors, such as cervical cancer, that drain to deep pelvic lymph nodes. Technique We injected technetium-99m colloidal albumin around the tumor allowing preoperative lymphscintigraphy and intraoperative gamma probe detection of sentinel nodes. For visual detection, blue dye was injected at the start of surgery. Experience In six of 10 eligible women who had Wertheim-Meigs operations for cervical cancer stage Ib, one or more sentinel nodes could be detected by scintigraphy. Intraoperative gamma probe detection was successful in eight of ten women, whereas visual detection found sentinel nodes in only four. They were found as far as the common iliac level. One woman had positive lymph nodes, of which one was a sentinel node. Conclusion Identification of sentinel nodes using radio-nuclide is possible in women with cervical cancer and potentially identifies women in whom lymph node dissection can be avoided.

Wait-and-see policy for the N0 neck in early-stage oral and oropharyngeal squamous cell carcinoma using ultrasonography-guided cytology: Is there a role for identification of the sentinel node?

Management of the N0 neck in patients with head and neck squamous cell carcinoma (SCC) remains controversial. We describe the outcome of patients who underwent transoral tumor excision and a wait‐and‐see policy for the neck staged N0 by ultrasonography‐guided cytology (USgFNAC). Because selection of lymph nodes for USgFNAC is currently based on size criteria, we investigated the additional value of sentinel node (SN) identification.

Sentinel Node Biopsy in Melanoma Patients: Dynamic Lymphoscintigraphy Followed by Intraoperative Gamma Probe and Vital Dye Guidance

Abstract. Biopsy of the first tumor-draining lymph node (sentinel node, SN) is bound to become the procedure of choice in regional staging of melanoma patients. A tumor-negative SN virtually excludes lymphatic metastases and obviates the need for lymph node dissection. The aim of this study was to combine the advantages of three known techniques to improve the yield of successful SN biopsies. A total of 150 drainage areas in 135 patients was evaluated. First, preoperative dynamic and static lymphoscintigraphy was performed after injection of technetium 99m colloidal albumin. In all patients one to three focal accumulations, concordant with SNs, were seen in the lymphatic drainage areas, in 97% within 20 minutes from injection of the tracer. Peroperative identification of the SN, 2 to 24 hours after injection of the tracer, was done with a handheld gamma probe to estimate the optimal site for the small incision and to guide preparation. Vital dye was injected just preoperatively and served to facilitate the final identification and biopsy of the SN. A total of 216 SNs were biopsied. Micrometastases were found in 39 SNs in 30 drainage areas, and in 22 of the 30 the SN was the only node harboring tumor. In 5 of 30 drainage areas, the SN did not contain blue dye and would not have been found without the gamma probe. Up to now (follow-up 233–691 days) no recurrence has developed in the lymphatic drainage areas where the SN was tumor-free. It was concluded that by combining these three techniques the SN could be detected and excised in all patients. The procedure combines a steep learning curve with high sensitivity.

Laparoscopic detection of sentinel lymph nodes followed by lymph node dissection in patients with early stage cervical cancer.

OBJECTIVE The purpose of this study was to investigate the feasibility of sentinel node detection through laparoscopy in patients with early cervical cancer. Furthermore, the results of laparoscopic pelvic lymph node dissection were studied, validated by subsequent laparotomy. METHODS Twenty-five patients with early stage cervical cancer who planned to undergo a radical hysterectomy and pelvic lymph node dissection received an intracervical injection of technetium-99m colloidal albumin as well as blue dye. With a laparoscopic gamma probe and with visual detection of blue nodes, the sentinel nodes were identified and separately removed via laparoscopy. If frozen sections of the sentinel nodes were negative, a laparoscopic pelvic lymph node dissection, followed by radical hysterectomy via laparotomy, was performed. If the sentinel nodes showed malignant cells on frozen section, only a laparoscopic lymph node dissection was performed. RESULTS One or more sentinel nodes could be detected via laparoscopy in 25/25 patients (100%). A sentinel node was found bilaterally in 22/25 patients (88%). Histological positive nodes were detected in 10/25 patients (40%). One patient (11%) had two false negative sentinel nodes in the obturator fossa, whereas a positive lymph node was found in the parametrium removed together with the primary tumor. In seven patients (28%), the planned laparotomy and radical hysterectomy were abandoned because of a positive sentinel node. Bulky lymph nodes were removed through laparotomy in one patient, and in six patients only laparoscopic lymph node dissection and transposition of the ovaries were performed. These patients were treated with chemoradiation. In two patients, a micrometastasis in the sentinel node was demonstrated after surgery. Ninety-two percent of all lymph nodes was retrieved via laparoscopy, confirmed by laparotomy. Detection and removal of the sentinel nodes took 55 +/- 17 min. Together with the complete pelvic lymph node dissection, the procedure lasted 200 +/- 53 min. CONCLUSION Laparoscopic removal of sentinel nodes in cervical cancer is a feasible technique. If radical hysterectomy is aborted in the case of positive lymph nodes, sentinel node detection via laparoscopy, followed by laparoscopic lymph node dissection, prevents potentially harmful and unnecessary surgery.

Reliability of the Sentinel Node Procedure in Melanoma Patients: Analysis of Failures After Long-Term Follow-Up

Background: The sentinel node (SN) concept assumes that early lymphatic metastases, if present, always are found first in the SN. The aim of this study was to determine the reliability ofthis procedure by establishing the success rate and number of failed procedures during a follow-up period of at least 2 years.Methods: From August 1993 to November 1996, 204 consecutive patients with stage I and II cutaneous melanoma underwent SN biopsy by a triple technique. Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma probe and blue dye helped localize the SN(s) during surgery, and these nodes subsequently were excised. These lymph nodes were step-sectioned and examined by routine and immunohistochemical staining. If the SN contained tumor cells, a lymphadenectomy was performed at a later date.Results: The median follow-up time was 42 months. The success rate was 99%. Three patients developed a recurrence in the negative SN basin during follow-up, without simultaneous appearance of (locoregional) metastases.Conclusions: With a 99% success rate and a 1.5% rate of failed SN procedures (7% falsenegative rate) after a median follow-up of 3.5 years, we concluded that the combined triple technique approach of detecting the SN was a reliable method to accurately identify and retrieve the SN.

Unpredictability of lymphatic drainage patterns in melanoma patients

Abstract We analysed the localisations of sentinel nodes (SN) found with the SN procedure to compare these sites with those that would have been predicted by conventional clinical descriptions of cutaneous lymphatic drainage. We assessed the surplus value of performing the SN procedure in melanoma patients who underwent regional nodal surgery. The SN procedure was performed in 348 patients with melanomas who were referred to our institute between 1993 and 1999. The localisations of the melanomas with the corresponding SNs were meticulously recorded on drawings of the human body and grouped according to the conventional descriptions. Predictability of lymph drainage was defined as the percentage of melanomas whose draining pattern was to the ipsilateral nearest basin, without simultaneous drainage to other basins or to an interval node. In all patients the SN procedure visualised at least one SN. We found 410 lymphatic basins in 347 patients. These basins included basins that could not have been predicted by the conventional clinical descriptions, such as multiple basins and contralateral drainage sites. For the head/neck region, SNs could be found in any of the basins described in the literature. The trunks drainage predictability depended strongly on the melanoma localisation, ranging from 0% in the midline to 92% in one of the upper quadrants. The lower extremities had a high predictability of almost 100%, and predictability of drainage for the upper extremities ranged from 77% to 100%. In total, 34% of the patients had a cutaneous lymphatic drainage that was unpredictable, either totally or partially. We therefore conclude that an SN procedure is indispensable if the drainage site(s) are to be accurately identified.

Pattern and incidence of first site recurrences following sentinel node procedure in melanoma patients

Studies of large series of melanoma patients indicated that the average incidence of developing a recurrence during follow-up was 40%. The most frequent first sites of these recurrences were the regional lymph nodes. We hypothesized that the sentinel node (SN) procedure may change the pattern of recurrence by reducing the number of first recurrences in the regional lymph node basin during follow-up to a negligible number, and that locoregional cutaneous and distance metastases are the major future sites of recurrence. We further studied the influence of SN status together with different influential factors on prognosis. An SN procedure with a triple technique was performed in 250 consecutive patients with proven AJCC stages I and II cutaneous melanoma. The median follow-up was 38 months. So far, 44 patients (18%) have developed a recurrence of the disease. The distribution of localization of the first metastases was as follows: 23 patients (52%) with a locoregional cutaneous recurrence; 4 (9%) with recurrence in the regional lymph node basin; 2 (5%) with recurrence in an interval node; and 15 (34%) with distant recurrence. The relative risk of developing recurrence for SN-positive patients is 4.2; for Breslow thickness of 1.51 to 4.00 mm it is 5.5, and thicker than 4.0 mm it is 6.2; for lymphatic invasion 7.6; and for ulceration 3.8. We conclude that the SN procedure changes the pattern of recurrences during follow-up by reducing the number of first recurrences within the regional lymph node basin to a negligible number. High Breslow thickness, lymphatic invasion, and ulceration of the primary melanoma are strong risk factors for recurrence.RésuméL’incidence de récidive de mélanome dans les grandes séries est de l’ordre de 40%. Ces récidives intéressent le plus souvent les ganglions lymphatiques régionaux. Notre hypothèse est que la technique de ganglion sentinelle (GS) réduit le nombre de récidives initiales dans le territoire de drainage direct alors que les récidives sont alors cutanées, locorégionales et à distance. Si cela était vrai, le nombre total de récidives pourrait être diminué. Nous avons étudié l’influence du GS et d’autres facteurs pronostiques. Chez 250 patients atteints de mélanome cutané stades I et II selon la classification AJCC, on a réalisé la technique de GS par la technique triple. La médiane de suivi a été de 38 mois. Jusqu’à présent, 44 patients (18%) ont développé une récidive. La distribution du site de la première métastase a été comme suit: récidive locorégionale cutanée 23 patients (52%), récidive régionale ganglionnaire: quatre (9%); récidive dans un ganglion intermédiaire: deux (5%); et récidive à distance 15 (34%). Le risque relatif (RR) de développer une récidive chez le patient GS positif a été de 4.2, de 5.5 chez le patient ayant un score de Breslow entre 1.51–4.0, et de 6.2 lorsque l’épaisseur a été de plus de 4 mm. Le RR a été de 6.2 en cas d’envahissement lymphatique et de 3.8 en cas d’ulcération. Nous concluons que la technique du GS réduit nettement l’incidence de récidive mais n’empêche pas le patient de développer une récidive. Le risque de développer une récidive lymphatique régionale est devenu rare. L’indexe élevé de Breslow, une invasion lymphatique et l’ulcération du mélanome primaire sont des facteurs prédictifs de récidive importants.ResumenLos estudios sobre grandes series de pacientes con melanoma indican que la tasa promedio de recurrencia primaria en el curso del seguimiento es 40%. El sitio más frecuente de recurrencia primaria es la zona de ganglios regionales. Hemos planteado la hipótesis de que la técnica del ganglio centinela (GC) reduce el número de recurrencias a los ganglios regionales a una cifra mínima, y que las metástasis a los ganglios locales-regionales y a distancia habrán de ser los lugares de recurrencia. Si esto resulta ser cierto, se podría reducir el número total de recurrencias. También estudiamos la influencia del estado del GC y la de otros factores sobre el pronóstico. En 250 pacientes consecutivos con melanoma cutáneo en estados I y II (AJCC) se realizó el procedimiento del GC mediante una técnica triple. El tiempo promedio de seguimiento fue 38 meses. Hasta el momento, 44 pacientes (18%) han desarrollado recurrencia, con la siguiente distribución: 23 pacientes (52%) con recurrencia local-regional cutánea, cuatro (9%) con recurrencia en la zona linfática-regional; 2 (5%) con recurrencia a un ganglio de intervalo; y 15 (34%) con recurrencia a distancia. El riesgo relativo de recurrencia en pacientes con GC positivo es 4.2; en melanomas con espesor de Breslow entre 1.51 y 5.5 mm y de más de 4.0 mm es 6.2; cuando hay invasión linfática el riesgo en 7.6; cuando hay ulceración es 3.8. Nuestra conclusión es que el procedimiento del GC ha reducido claramente la incidencia de recurrencia, aunque ello no quiere decir que prevenga la recurrencia en todos los pacientes. La recurrencia ganglionar local-regional aparece poco común. Un espesor de Breslow grueso, la invasión linfática y la ulceración del melanoma primario son todos factores fuertes de riesgo de recurrencia.