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Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: A Novel Concept

Crane LM, Themelis G, Pleijhuis RG, Harlaar NJ, Sarantopoulos A, Arts HJ, van der Zee AG, Ntziachristos V, Vasilis N, van Dam GM - Mol Imaging Biol (2011)

Bottom Line: Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue.None of the non-fluorescent LNs contained metastases.We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible.

Affiliation: Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands.

ABSTRACT

Purpose: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer.

Procedures: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system.

Results: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases.

Conclusions: We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible. However, the technique needs to be refined for full applicability in cervical cancer in terms of sensitivity and specificity.

Lymph drainage of the cervix uteri is complex, bilateral, and can affect lymph nodes in several areas. In our pilot study, nine SLNs were found. These were localized in the left obturator fossa (three), right obturator fossa (two), left external iliac (one), right external iliac (one), right common iliac (one), and on the junction of the right internal iliac and obturator fossa (one).
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Fig1: Lymph drainage of the cervix uteri is complex, bilateral, and can affect lymph nodes in several areas. In our pilot study, nine SLNs were found. These were localized in the left obturator fossa (three), right obturator fossa (two), left external iliac (one), right external iliac (one), right common iliac (one), and on the junction of the right internal iliac and obturator fossa (one).

Mentions: The prognosis of early stage cervical cancer is substantially influenced by lymph node (LN) status, with positive LNs adding to an unfavorable prognosis [10, 11]. Standard surgical treatment therefore consists of radical hysterectomy combined with bilateral pelvic lymphadenectomy. Metastatic involvement is found in no more than 13–27% of the LNs [1, 11], implying that radical pelvic lymphadenectomy can be regarded as overtreatment without clinical benefit in more than three quarters of the patients. Moreover, LN dissection may have the unfavorable consequence of lymphedema of the legs, occurring in 14–32% of patients [12, 13]. The SLN procedure could lead to more selective LN dissection, but its definitive value in cervical cancer is still a matter of debate and subject of ongoing investigation. The reliability in terms of sensitivity has improved markedly in the last two decades, mainly due to the combination of a radioactive tracer combined with a blue dye rather than using blue dye alone [14]. This bimodal approach yields false negative rates of 0% in tumors <2 cm [15, 16]. Although these data are encouraging, SLN detection in the pelvic region remains complicated due the bilateral and not fully predictable lymphatic routing originating from the uterine cervix. About 80% of SLNs are found in the area of internal and external iliac nodes and in the obturator fossa, but involvement of lymph nodes in the parametrium and para-aortal regions has also been reported (Fig. 1) [17–20]. Bilateral SLNs are found in 59–66% of patients [15, 16]. In particular, the blue dye can be difficult to trace in extrapelvic areas because of overlying muscle tissue or fat.Fig. 1

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Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: A Novel Concept

Crane LM, Themelis G, Pleijhuis RG, Harlaar NJ, Sarantopoulos A, Arts HJ, van der Zee AG, Ntziachristos V, Vasilis N, van Dam GM - Mol Imaging Biol (2011)

Lymph drainage of the cervix uteri is complex, bilateral, and can affect lymph nodes in several areas. In our pilot study, nine SLNs were found. These were localized in the left obturator fossa (three), right obturator fossa (two), left external iliac (one), right external iliac (one), right common iliac (one), and on the junction of the right internal iliac and obturator fossa (one).
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Fig1: Lymph drainage of the cervix uteri is complex, bilateral, and can affect lymph nodes in several areas. In our pilot study, nine SLNs were found. These were localized in the left obturator fossa (three), right obturator fossa (two), left external iliac (one), right external iliac (one), right common iliac (one), and on the junction of the right internal iliac and obturator fossa (one).
Mentions: The prognosis of early stage cervical cancer is substantially influenced by lymph node (LN) status, with positive LNs adding to an unfavorable prognosis [10, 11]. Standard surgical treatment therefore consists of radical hysterectomy combined with bilateral pelvic lymphadenectomy. Metastatic involvement is found in no more than 13–27% of the LNs [1, 11], implying that radical pelvic lymphadenectomy can be regarded as overtreatment without clinical benefit in more than three quarters of the patients. Moreover, LN dissection may have the unfavorable consequence of lymphedema of the legs, occurring in 14–32% of patients [12, 13]. The SLN procedure could lead to more selective LN dissection, but its definitive value in cervical cancer is still a matter of debate and subject of ongoing investigation. The reliability in terms of sensitivity has improved markedly in the last two decades, mainly due to the combination of a radioactive tracer combined with a blue dye rather than using blue dye alone [14]. This bimodal approach yields false negative rates of 0% in tumors <2 cm [15, 16]. Although these data are encouraging, SLN detection in the pelvic region remains complicated due the bilateral and not fully predictable lymphatic routing originating from the uterine cervix. About 80% of SLNs are found in the area of internal and external iliac nodes and in the obturator fossa, but involvement of lymph nodes in the parametrium and para-aortal regions has also been reported (Fig. 1) [17–20]. Bilateral SLNs are found in 59–66% of patients [15, 16]. In particular, the blue dye can be difficult to trace in extrapelvic areas because of overlying muscle tissue or fat.Fig. 1

Bottom Line: Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue.None of the non-fluorescent LNs contained metastases.We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible.

Affiliation: Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands.

ABSTRACT

Background:

Purpose: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer.

Procedures: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system.

Results: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases.

Conclusions: We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible. However, the technique needs to be refined for full applicability in cervical cancer in terms of sensitivity and specificity.

View Similar Images In: Results  - Collection
View Article: Medline Plus - Pubmed Central -  PubMed
Show All Figures - Show MeSH
getmorefigures.php?pmc=3179588&rFormat=json&query=null&req=5