Cervical cancer is the third most common gynecologic malignancy, with almost 13,000 newly diagnosed cases per year in the United States and 4,400 related deaths. In patients with stage IA2-IB1 disease, the rate of lymph node metastases averages 15%. Thus, as in vulvar cancer, the majority of cervical cancer patients subjected to a complete lymph node dissection do not derive clear benefit from it yet the procedure is associated with potentially serious complications (eg, lymphocysts and adhesion formation, pain, paresthesia, vascular damage, and lymphedema), particularly if it is followed by adjuvant radiation therapy.
The technique for sentinel node mapping in cervical cancer is similar to that described for vulvar cancer.The Tc-99 is injected very superficially at the periphery of the tumor, or in the four quadrants of the cervix, using a 25-gauge spinal needle, 3½- in. long. To facilitate the injection and render the spinal needle more stiff, a second spinal needle (20- gauge, 2-in. long) is slid over the first one and secured with Steri-Strips. Alternatively, a rigid needle extender such as those used for pudendal blocks can be used. Care is taken to avoid injecting the radiocolloid into the tumor itself.
A lymphoscintigram is performed 30 minutes after the injection. (In our experience, dynamic studies have shown that sentinel nodes can readily be seen as early as 15 minutes after the injection). Because the nodes are located deep in the pelvis, skin marking of the sentinel node is not reliable. However, it is useful to have the hard-copy lymphoscintigram available in the operating room to help search for the sentinel node, particularly when it appears to be in an aberrant location.
The blue dye is injected just before the surgery. After induction of general anesthesia, 2 to 4 mL of isosulfan blue dye is injected superficially in the four quadrants of the cervix. After completing the dye injection, a regular rectovaginal examination is performed. The patient is then prepped and draped, and the sentinel node exploration begins immediately. It can be performed via an abdominal incision (laparotomy) or by laparoscopy. Only the laparoscopic approach will be described here.
After insertion of the four trocars, the retroperitoneum on one side is opened. Blue lymphatics emerging from the lateral parametrium, usually crossing over the obliterated umbilical artery, are followed all the way to their ending in a blue node, which is considered to be the sentinel node. Occasionally, more than one sentinel node is identified per side. Before removing the blue nodes, the laparoscopic gamma probe is inserted through the suprapubic 10-mm port (eg, Versaport 5-10, Autosuture). Counts are first obtained on the blue node and recorded. The node is then retrieved, and extracorporeal counts are performed again on that node for confirmation. The laparoscopic probe is reintroduced, and the pelvic walls are scanned in a search for other signals.
The same procedure is performed on the contralateral side. In cases where the dye injection did not work well and no blue nodes are identified at laparoscopy, a detailed exploration of the pelvic sidewalls with the laparoscopic gamma probe is performed along the major blood vessels, including the common iliac, presacral, and lower para-aortic areas, to search for a radioactive signal. The preoperative lymphoscintigram is useful in these cases, to help identify the approximate location of the sentinel node.
• Assessment—All sentinel nodes are sent for immediate frozen section. If they are negative, a complete bilateral pelvic node dissection is completed laparoscopically, as sentinel node mapping is not considered the standard of care. Radical surgery follows (either abdominal or vaginal radical hysterectomy or radical trachelectomy). If the sentinel nodes are positive, a bilateral para-aortic node dissection is performed, but radical surgery is abandoned in favor of combined chemoradiation.
The sentinel node mapping performed via an abdominal incision is identical, except that a handheld gamma probe is used.
Review of the Literature
Sentinel node mapping was developed more recently in cervical cancer. Twelve studies have been published since 1999, totaling 323 cases,[12,35-45] but most of these series have included a small number of patients. Moreover, the technique used for sentinel node mapping, patient selection criteria, surgical approach, and sentinel node pathologic evaluation vary among the studies. Nevertheless, these preliminary studies indicate that sentinel node mapping is feasible in cervical cancer.
With the exception of the first study, the overall sentinel node detection rate ranges from 60% to 100% (Table 3). Several studies convincingly demonstrate the superiority of the combined blue dye/preoperative lymphoscintigraphy technique to improve the sentinel node detection rate.[36,41,43,45] Indeed, in Malur's study, the sentinel node detection rate with the blue dye alone was only 55%; with the radiolabeled Tc-99, it increased to 76%, and with the combined technique, it reached 90%. Levenback et al reported a 100% detection rate with the combined technique, whereas in their preliminary report using the blue dye alone, the detection rate was only 60%.[38,43] In the study by Verheijen et al, the detection rate improved from 40% to 80% with the addition of lymphoscintigraphy compared to the blue dye alone. In our own experience, the sentinel node detection rate increased from 79% to 93% with the combined technique.
Lymphatic Drainage and Sentinel Node Localization
The lymphatic drainage of the cervix is much more complex than that in vulvar or breast cancer. Indeed, studies by Plentl and Friedman showed that there are three main trunks arising on each side of the cervix: the lateral, anterior, and posterior collecting trunks. The lateral trunk, which is the main lymphatic pathway, further divides into the upper, middle, and lower branches. Therefore, the search for the sentinel node must be very meticulous, and because the lymphatic drainage of the cervix is more haphazard, lymphoscintigraphy is particularly useful.
Because the cervix is a midline structure, it would seem logical that the lymphatic drainage should be bilateral in most cases. This assumption is based on the pioneering work of Leveuf and Godard, who showed that when the cervix is injected anteriorly and posteriorly, the lymphatic drainage is bilateral. Others refute the sentinel node concept in cervical cancer altogether, concluding that the pattern of lymphatic drainage in early-stage cancer of the cervix is completely random.
• Common Sites—The localization of the sentinel node in cervical cancer is more variable than in vulvar cancer for the reasons mentioned above. The three most frequent sentinel node sites for cervical cancer are the external iliac nodes (Leveuf and Godard's "intermediate"), followed by the obturator nodes ("caudal"), and the bifurcation nodes ("cephalad").[ 36,38-43,45,47] Parametrial nodes, considered in-transit nodes between the cervix and the pelvic nodes, are particularly difficult to identify because of the proximity of the cervix, where the blue coloration is intense and the radioactivity high.[45,47]
Occasionally, sentinel nodes are identified at the common iliac, at the level of the internal iliac artery alongside the ureter, or even in the lower para-aortic region. These more uncommon patterns of spread can easily be explained by the lymphatic drainage arising from the lower branch of the lateral collecting trunk and/or from the posterior collecting trunk. Unusual sites of metastasis such as the groin-probably secondary to retrograde lymphatic drainage-have also been reported by two groups.[42,49]
Figure 2 shows examples of various sentinel node localizations. First, a lymphoscintigram is done 20 minutes after an intracervical Tc-99 injection, showing in this case a bilateral sentinel node uptake with continued uptake on the left side toward the left para-aortic region (Figure 2A). A right external iliac blue sentinel node with the blue lymphatic entering it is easily visible (Figure 2B). A right obturator blue sentinel node is discovered after opening the obturator fossa (Figure 2C). In addition, a right parametrial blue sentinel node is found, with a blue lymphatic vessel continuing under the superior vesical artery and ending in the obturator fossa (Figure 2D). The ureter can be seen just on the left of the parametrial sentinel node. The gamma probe also confirmed a very hot signal.
Figure 2E shows an unusual sentinel node location in the left presacral area. In that case, no sentinel nodes were identifed upon thorough exploration of the left retroperitoneal area; however, scanning of the lower paraaortic region with the laparoscopic gamma probe identified a hot area with a faint blue stain in the left presacral area (Figure 2E). Detailed exploration confirmed the presence of a sentinel node medial to the common iliac vein, which was pale blue and very hot. Note the complete dissection of the common iliac artery (Figure 2F). This case illustrates the importance of a thorough sentinel node search and the advantage of the gamma probe when no blue nodes are identified. Unusual lymphatic drainage sites probably explain some situations where all the pelvic nodes removed in a patient are negative, yet the patient develops a recurrence in the lower para-aortic region sometime later.
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