Studies On Lymphatic Mapping And Sentinel Lymphadenectomy In Patients With Vulvar Cancer

DiSaia in 1979 was the first to postulate that the superficial groin nodes may serve as sentinel lymph nodes for more deeply situated nodes in patients with vulvar cancer [18]. Patients with clinically normal nodes underwent intraoperative mapping through a modified incision. No complete lymphadenectomy was performed if frozen-section analysis of the superficial lymph nodes did not show metastasis. However, in later studies of early vulvar cancer, femoral node metastasis was reported after biopsy of tumor-free superficial inguinofemoral nodes [44].

In 1983, Iversen and Aas presented a scintigraphy study of lymph drainage of the vulva in patients with cervical cancer scheduled for radical surgery [45]. The conclusions of this study were as follows: in all patients, the vulvar lymph flow passes to the inguinofemoral and pelvic lymph nodes; clitoris and perineum have bilateral drainage; the main lymphatic pathway is ipsilateral after injection in the labium, but nearly 70% also have some contralateral lymph drainage; and no direct pathways to pelvic nodes exist with bypassing of the inguinofemoral nodes. A subsequent pilot study was undertaken in vulvar cancer patients to correlate patterns of lymphatic drainage with clinical and histopathological findings of the inguinofemoral lymph nodes [46]. However, radioactive tracer uptake patterns in the inguinofemoral lymph nodes were not predictive for the presence or absence of metastases.

In 1994, Levenback and co-workers published the first feasibility study of sentinel node biopsy using isosulfan blue in nine patients with vulvar cancer [47]. No technique-related complications were observed and the sentinel lymph node status was indicative of the lymph basin status in all patients. Extension of the study to 21 patients showed that the sentinel lymph node technique with isosulfan blue was a safe and simple technique and that it allowed identification of the sentinel node in 66% of the dissected groins [48]. In 1997, DeCesare and coworkers reported a pilot study on intraoperative gamma-ray detection for identification of the sentinel node [49]. After induction of general anesthesia, a techne-tium-99m ("mTc)-labeled nanocolloid (Nanocoll®, Sorin Radiofarmaci S.r.l., Saluggia, Italy) was injected around the tumor. A hand-held gamma detection probe (Neoprobe 1000®, Neoprobe Corporation, Dublin, OH) was used for identification of the first-tier node. This technique correctly indicated the nodal status in all four cases with metastatic inguinofemoral dissemination and in all 16 groins without disease. The 99mTc-labeled colloid had to be injected at least 1 h before the procedure in order to allow the background radiation in the groin to decrease sufficiently for the sentinel lymph node to be identified.

At our institution, a feasibility study involving 11 patients was performed to determine whether the sentinel node could be identified using a combination of a preoperatively administered 99mTc-labeled nanocolloid and intraoperatively administered patent blue dye (Blue Patente V, Guerbet, Aulney-Sous-Bois, France) [50]. Lymphoscintigraphy was performed on the day before the operation, with a peritumoral injection of a 99mTc nanocolloid. The first-appearing persistent focal accumulation was designated as the sentinel lymph node. The location of this sentinel lymph node was marked on the overlying skin. The subsequent day, patent blue dye was injected intradermally around the primary tumor, approximately 10 min prior to the surgical resection. A hand-held gamma detection probe was used during the operation to localize the sentinel lymph node. After removing the sentinel lymph node(s), complete inguinofemoral lymphade-nectomy was performed and these lymph nodes were sent for histopathological examination separately. In 10 evaluable patients, preoperative administration of the 99mTc nanocolloid was well tolerated. One patient refused further participation just before the injection of the radioactive tracer because of anxiety about pain. All 18 sentinel lymph nodes were identified with the probe. Ten of the 18 nodes were stained blue or had a blue-stained lymphatic duct leading up to them (56%). The inguinofemoral lymph nodes were free of disease in eight patients, and both sentinel and nonsentinel nodes contained metastatic disease in the remaining two patients. We concluded that identification of the sentinel lymph node is feasible in patients with vulvar cancer by the combination of a preoperatively administered 99mTc-labeled nanocolloid and intraoperatively administered blue dye (see case report and Figs. 2 and 3).

Two other feasibility studies concerning identification of the sentinel lymph node in vulvar cancer with comparable results were published [51,52]. Recently, Ansink et al. published a multicenter study to investigate the negative predictive value of the sentinel node procedure in 51 patients [53]. Only blue dye was used, l r

Table 2 Studies on Lymphatic Mapping of Squamous Cell Carcinoma of the Vulva

Patients

SLNa found

False negative

Study [Ref.]

(n)

Tracer

Blue dye

Scintigraphy

(groins)

SLN

Levenback et al. 1995 [48]

21

no

yes

no

66%

0

DeCesare et al. 1997 [49]

10

yes

no

no

100%

0

De Cicco et al. 1997 [51]

15

yes

no

yes

100%

0

de Hullu et al. 1998 [50]

10

yes

yes

yes

100%

0

Rodier et al. 1999 [52]

8

yes

yes

yes

100%

1

Ansink et al. 1999 [53]

51

no

yes

no

56%

2

a SLN = sentinel lymph node.

mph 3-Q

mph 3-Q

my a SLN = sentinel lymph node.

and the identification of sentinel lymph nodes was successful in only 56% of the groins. Moreover, in two patients false-negative sentinel lymph nodes were found. (See Table 2 for a summary of the studies). In this multicenter study, five referral centers participated. However, three of the five centers included less than 10 patients, and it is generally accepted that there is a learning curve in performing the SLN procedure. Morton suggested a learning phase of at least 30 consecutive cases per center for cutaneous melanoma. In view of the fact that there are only minimal variations in the anatomy of lymph flow in vulvar cancer to the inguinofemoral lymph nodes (compared with the sometimes unpredictable lymph flow of cutaneous melanoma), the learning curve will probably be steeper, but at least the first 10 patients (with SLN procedures in 10-20 groins), should be regarded as the learning phase for the SLN procedure in vulvar cancer.

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