Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection.

ORIGINAL STUDY

Detection of Sentinel Nodes for Endometrial Cancer With Robotic Assisted Fluorescence Imaging: Cervical Versus Hysteroscopic Injection Emma C. Rossi, MD,* Amanda Jackson, MD,Þ Anastasia Ivanova, PhD,þ and John F. Boggess, MDÞ

Objective: Sentinel lymph node (SLN) mapping with indocyanine green (ICG) detected by robotic near infrared (NIR) imaging is a feasible technique. The optimal site of injection (cervical or endometrial) for endometrial cancer has yet to be determined. We prospectively evaluated SLN mapping after cervical and endometrial injections of ICG to compare the detection rates and patterns of nodal distribution. Methods: Twenty-nine subjects with endometrial cancer undergoing robotic hysterectomy with lymphadenectomy by a single surgeon received SLN mapping with robotic fluorescence imaging. Seventeen patients received cervical injections of 1 mg of ICG and 12 patients received hysteroscopic endometrial injections of 0.5-mg ICG. Detection rates between the 2 groups were compared using Fisher exact tests. Continuous variables such as operating room times and body mass index were compared using t tests. Results: The SLN detection rate was 82% (14/17) for cervical and 33% (4/12) for hysteroscopic injection (P = 0.027). Sentinel lymph nodes were seen bilaterally in 57% (8/14) of the cervical injection group and 50% (2/4) of the hysteroscopic group. Para-aortic SLNs were seen in 71% (10/14) of patients who mapped after cervical injection and 75% (3/4) patients who mapped after hysteroscopic injection. There was 1 false-negative SLN in the cervical injection group. Conclusions: Cervical ICG injection achieves a higher SLN detection rate and a similar anatomic nodal distribution as hysteroscopic endometrial injection for SLN mapping in patients with endometrial cancer. Key Words: Sentinel lymph nodes, Endometrial cancer, Robotic surgery Received June 5, 2013, and in revised form July 18, 2013. Accepted for publication July 21, 2013. (Int J Gynecol Cancer 2013;23: 1704Y1711)

are increasing data to suggest that sentinel lymph T here node (SLN) mapping for endometrial cancer is a sensitive

site for dye injection is controversial. Subserosal, hysteroscopically guided endometrial, and cervical injections have all been studied.1 The theoretical benefit of endometrial injections is the

*Division of Gynecologic Oncology, Indiana University Health Melvin and Bren Simon Cancer Center, Indianapolis, IN; †Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC; and ‡Department of Biostatistics, University of North Carolina, Chapel Hill, NC.

Address correspondence and reprint requests to Emma C. Rossi, MD, Indiana University Department of Obstetrics and Gynecology, Indiana Cancer Pavilion, Indiana University Medical Center, 535 Barnhill Dr, Indianapolis, IN 46303-5274. E-mail: [email protected]. Supported by the University of North Carolina Lineberger Comprehensive Cancer Center Clinical Translational Cancer Research Award and the National Center for Research Resources through the NIH Clinical and Translational Science Award (CTSA). The authors declare no conflicts of interest.

tool in detecting lymph node metastases; however, the optimal

Copyright * 2013 by IGCS and ESGO ISSN: 1048-891X DOI: 10.1097/IGC.0b013e3182a616f6

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International Journal of Gynecological Cancer

& Volume 23, Number 9, November 2013

Copyright © 2013 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.


& Volume 23, Number 9, November 2013 Sentinel Nodes for Endometrial Cancer

proximity to the tumor site; however, it is technically challenging and requires an additional hysteroscopic procedure. Alternatively, cervical injections are more technically straightforward; however, they are remote from the tumor, and raise concerns about validity. The traditional techniques of SLN mapping are visible blue dyes (such as isosulfan or methylene blue) with or without radiolabeled isotopes such as technetium 99 (Tc99) microsulfur colloid. These traditional techniques can be challenging to master with prolonged learning curves.2 The use of near infrared (NIR) imaging to detect fluorescing dye, such as indocyanine green (ICG), is a feasible alternative to the traditional methods of lymph node mapping in endometrial cancer.3 The benefits of this technology are that it combines the benefits of the blue dye technique (visibility) and nuclear medicine techniques (penetration of signal through intact tissue) with a single modality. Near infrared imagers have been investigated for gynecologic SLN mapping surgeries performed via laparotomy, laparoscopy, and robotic assisted laparoscopy.3Y6 We used an NIR imager integrated into the surgical robot to compare the mapping of SLNs in patients with endometrial cancer after hysteroscopic or cervical injections. We hypothesized that cervical injections of ICG would be a feasible method of SLN detection with a similar detection rate and a comparable anatomic distribution to hysteroscopic injection.

MATERIALS AND METHODS Permission was obtained from the institutional review board (IRB) to perform a prospective cohort study of women with a preoperative diagnosis of clinical stage I endometrial cancer. All endometrial cancer grades and histologies were included. All patients received SLN mapping using robotic assisted fluorescence imaging. A SLN was defined as any nodular tissue (ie, excluding the lymphatic channels) that appeared fluorescent green. This included lymph nodes that were first in chain (true sentinel nodes), as well as upper echelon nodes which consisted of fluorescent green lymph nodes that resided distal to first in chain nodes, along the same channels (eg, common iliac or para-aortic nodes downstream from an obturator or internal iliac node). All visible green nodes were dissected and labeled as SLNs regardless of their relationship to other nodes in the chain. Fluorescence imaging uses dyes or fluorophores, such as ICG, that fluoresce in the NIR light range. When a laser emitted from the NIR imager excites ICG, it produces a wavelength that, when returned to the imager, is converted to a fluorescent image. The imagers that were used in this study, the SPY scope (Novadaq Technologies Inc.) and the Fluorescence Imaging for the da Vinci Si (Intuitive Surgical, Inc), integrate the signal onto the white light or grayscale background image, so that the surgeon can see both the fluorescent signal and the surrounding anatomy, allowing them to perform the mapping and dissection simultaneously. The real-time visual mapping is similar to traditional blue dyes. However, ICG is undetectable in visible white light at the doses used for lymphatic mapping, which preserves the

surgeon’s view of the anatomy as normal. The fluorophore is able to penetrate intact tissue, which is also a virtue of radiocolloids. However, robotic fluorescence imaging provides continuous visual feedback and integrates the mapping and operating modes so that surgeon can identify the lymphatic channels and nodes through tissue while simultaneously performing the dissection. The first 17 successive subjects were consented to receive cervical stromal injections of ICG, a nontoxic, watersoluble tricarbocyanine dye, with their surgical staging procedure. The following 12 sequential patients were consented to undergo hysteroscopically guided endometrial injections. All patients had a planned robotic assisted type I hysterectomy with bilateral salpingo-oophorectomy, and bilateral pelvic and paraaortic lymphadenectomy. Para-aortic lymphadenectomy was aborted if it could not be performed due to limitations in visualization of the para-aortic basins. A single surgeon performed all cases. Injection of dye was performed after induction of anesthesia for both cohorts. A 0.5-mg/mL concentration of ICG was used for all patients. The doses of ICG used were 1 mg for cervical injection and 0.5 mg for endometrial injection. A larger cervical dose was prescribed due to the anticipated decreased lymphovascular density of the cervical stroma in comparison to the endometrium. The maximum IRBapproved dose for cervical injection was 0.75 mg and was exceeded by the patients in this study who received 1-mg ICG cervical injections, representing protocol deviations. The protocol was subsequently amended by the IRB to approve 1-mg doses. The patients in the cervical injection cohort received 0.5-mg doses of ICG delivered with a 21-gauge spinal needle at a 1-cm depth to the cervical stroma at 3 o’clock and 9 o’clock for a total dose of 1 mg. After ICG injection, the skin incisions were made, and the robot was docked, at which time the NIR system was activated and nodal mapping was performed. The procedural steps differed for the patients in the endometrial injection cohort. After induction of anesthesia, the robotic ports were placed and laparoscopy was performed. The fallopian tubes were sealed with a bipolar energy source. Hysteroscopy was then performed and an 18-gauge 500-mm oocyte recovery set needle with attached tubing (Smith Medical ASD, Inc) primed with ICG was inserted through the operative port. The needle was inserted to a 5-mm depth (which was identified by a notch at the needle’s tip) at multiple sites immediately lateral to the boundary of normal and abnormal appearing endometrium. A total dose of 0.5 mg of ICG was administered peritumorally. The robotic system was docked to the ports after hysteroscopy was completed, and the NIR imaging system was activated to allow for nodal mapping. Seven patients in the cervical injection cohort had mapping performed with a hand held endoscopic NIR imager called SPY scope (Novadaq Technologies Inc). The subsequent 22 subjects all had nodal mapping using the fluorescence imager for the da Vinci Si (Intuitive Surgical, Inc). Sentinel lymph nodes were identified by subjective visual assessment. Lymphatics and nodes containing ICG were seen

* 2013 IGCS and ESGO


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as green fluorescence on a background of a grayscale image (Fig. 1). A minimum of 10 minutes after dye injection was allowed to elapse before any retroperitoneal dissection took place. The pelvic peritoneum was first opened to identify proximal SLNs and their channels. To prevent spillage, these afferent and efferent channels were sealed with bipolar or monopolar energy before removal of the SLN. The para-aortic basins were explored after the pelvic basins to avoid interrupting dye transit from the pelvis to the para-aortic nodes. A mapping was described as positive if any green nodes (unilateral or bilateral) were seen. A mapping was described as negative if no SLNs were observed 30 minutes after the injection of ICG. This time frame was selected to minimize patient exposure to increased operating room time while allowing for ICG to reach the SLN, and was supported by our prior observations of the speed of dye transit.3 Completion lymphadenectomy was performed on all patients. All identified SLNs were analyzed with permanent histopathology. Sentinel lymph nodes were ultrasectioned at 2- to 3-mm intervals and placed in cassettes. Three hematoxylin and eosin levels were obtained of each tissue block. Immunohistochemistry evaluation of negative SLNs was not performed in this study. Lymphadenectomy specimens were evaluated in their entirety. The procedural data collected included the number and anatomic location of SLNs detected, and the duration of surgery. Demographic and pathologic information was also prospectively collected. Detection rates between the 2 groups were compared using 2-sided Fisher exact test. Continuous variables such as lymph node counts, operating room times and body mass index were compared using t tests.

RESULTS Twenty-nine patients had mapping attempted between November 2011 and September 2012, with 17 in the cervical injection cohort and 12 in the endometrial injection cohort. Table 1


summarizes the demographic and clinicopathologic characteristics of all 29 subjects. All patients underwent complete pelvic lymphadenectomy. A para-aortic lymph node dissection was performed on 83% of patients. The median number of pelvic and para-aortic non-SLNs removed was 18 (range, 0Y41) and 11 (range, 0Y20) and was equivalent between the 2 cohorts. The detection rate for at least 1 SLN was 82% (14/17) for the cervical injection cohort, versus 33% (4/12) for the endometrial injection cohort (P = 0.027) (Table 2). Among patients who successfully mapped, the median number of SLNs mapped was 5 for the cervical injection cohort (range, 1Y9) and 2.5 for the hysteroscopic injection cohort (range, 1Y3) (P = 0.08). Sentinel lymph nodes were seen bilaterally in 57% (8/14) of the cervical injection group and 50% (2/4) of the hysteroscopic group. Figure 2 illustrates the anatomic location of SLNs mapped after (a) cervical injection and (b) hysteroscopic injection. The most common pelvic SLN location after cervical injection was internal iliac (including medial to the iliacs) followed by obturator and common iliac. The most common pelvic SLN location after hysteroscopic injection was external iliac followed by internal iliac and obturator. Para-aortic SLNs were seen in 71% (10/14) of patients who mapped after cervical injection and 75% (3/4) patients who mapped after hysteroscopic injection. Isolated para-aortic SLNs were identified in the absence of pelvic SLNs in 2 of 18 patients. One of these patients with isolated para-aortic fluorescent nodes had bilaterally identified SLNs. Patients had SLNs identified above the IMA in the infrarenal para-aortic basin (including 3 with cervical injections and 1 with hysteroscopic injection). A total of 9 SLNs in 24% of patients were located outside the characteristic boundaries of pelvic or para-aortic lymphadenectomy as described by the GOG surgical handbook,7 for example, deep to the obturator nerve, or in the presacral space. All patients had clinical stage I endometrial cancer on preoperative pathology. One patient (in the cervical injection

FIGURE 1. Lymphatic mapping with NIR imaging of the right pelvis after injection of ICG into the uterine cervix.

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TABLE 1. Demographic and clinicopathologic data (n = 29 cases)

Age, median (range), y BMI, median (range), kg/m2 Histology (no. cases) Endometrioid Grade 1 Grade 2 Grade 3 Serous Carcinosarcoma Other FIGO stage (no. cases, endometrial only) Stage I Stage II Stage III Stage IV Para-aortic node dissection performed (%) Number of pelvic nodes (mean, non-SLN) Number of para-aortic nodes (non-SLN) Time in operating room, min

Cervical Injection

Hysteroscopic Injection

P

62 (21Y50) 33 (28Y82)

63.5 (55Y79) 32 (24.8Y49.5)

NS NS NS

11 7 2 2 3 2 1

11 6 2 3 1 0 0

13 0 3 0 14 (82) 17.5 (T8) 10.3 (T6) 186 (T28.6)

11 0 1 0 10 (83) 17.3 (T7) 10.6 (T6) 207.5 (T49.6)

NS

NS NS NS 0.15

BMI, body mass index.

cohort) was found to have stage IIC serous fallopian tube cancer with cervical tumor infiltration on final pathology. Figure 3 illustrates the outcomes of nodal evaluation for patients following (a) cervical injection and (b) hysteroscopic injection. Four

patients had stage IIIC endometrial cancer (3 in the cervical injection cohort and 1 in the hysteroscopic cohort). A SLN was identified in 2 of these 4 women (both receiving cervical injections). One of these patients with stage IIIC disease and

TABLE 2. Sentinel node mapping data (n = 29 cases)

SLN identified (% of cases) Yes No No. SLNs identified, median (range) Location of SLN (% of cases) Pelvis Para-aortic Pelvis and para-aortic Laterality of SLNs (% of cases with SLNs) Left Right Bilateral Patients with metastatic nodes, n (%) SLN +/non-SLN + SLN j/non-SLN + No SLN mapped Total

Cervical Injection

Hysteroscopic Injection

14 (82) 3 (18) 5 (1Y9)

4 (33) 8 (66) 2.5 (1Y3)

4 (24) 1 (6) 9 (53)

1 (8) 1 (8) 2 (17)

2 (14) 2 (14) 10 (72)

1 (25) 1 (25) 2 (50)

1 (6) 1 (6) 1 (6) 3 (18)

0 0 1 (8.3) 1 (8.3)

P 0.027

0.08 NS

NS



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FIGURE 2. Anatomic distribution of SLNs detected with fluorescence-guided NIR imaging. A, Cervical injection. B, Hysteroscopic injection. successful node mapping had a negative left pelvic SLN with a positive right pelvic node in the lymphadenectomy specimen representing a false-negative SLN. The negative predictive value for SLNs identified with cervical ICG injection was 92%. There was nonsignificant trend toward an increase in mean operating room time for the hysteroscopic injection group (185 vs 207 minutes).

DISCUSSION Assessment of lymph nodes for metastatic disease is important in the staging of endometrial cancer8 and serves to guide adjuvant therapy. However, the role of systematic lymphadenectomy in endometrial cancer remains controversial.9 Lymph node mapping, or SLN biopsy, for endometrial cancer may provide benefits over traditional lymphadenectomy. There is increased detection of metastatic disease in SLNs compared with randomly collected lymphadenectomy specimens,10 which may be secondary to the more rigorous pathologic assessment techniques used to evaluate SLNs for metastatic disease. Additionally, node mapping techniques may reveal relevant lymph nodes that contain occult metastatic disease but reside outside the traditional boundaries of standardized lymphadenectomy; 24% of patients in our series had nodes mapped in regions that would not otherwise have been routinely assessed. In theory, a less radical nodal dissection may reduce perioperative and long-term morbidity, as is the case for SLN assessment in breast cancer.11 Indeed, SLN mapping has become routine practice in the surgical management of early stage breast and melanoma cancers.12,13 What differs between

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endometrial cancer and these lateralized cutaneous tumors is that endometrial cancers are centralized with variable, bilateral lymphatic drainage patterns. They reside deep within a pelvic organ and are difficult to access and visualize. The accuracy of SLNs in identifying metastatic disease for endometrial cancer has been studied in large prospective and retrospective series.2,14 Sentinel lymph node detection rates were reported between 85% and 89%, with 50% of nodes mapped bilaterally. The sensitivity for the detection of metastatic disease ranged between 83% and 100%, with the highest sensitivity and negative predictive value found when the results of mapping are separately analyzed as left or right pelvic basins.14 These large studies used traditional techniques of radiocolloids and, or, visible blue dyes injected into the uterine cervix. They provide promising results; however, questions remain. Our research aimed to address the following 2 questions: can cervical injections achieve comparable detection rates and anatomic distribution to endometrial injections, and can the novel technique of NIR imaging with fluorescent dyes reproduce the detection rates and anatomic distribution of SLNs seen with traditional techniques in endometrial cancer? There is debate regarding the optimal site of dye injection, cervical versus endometrial, in node mapping for endometrial cancer. Opponents of the cervical approach raise concerns that the cervix is remote and may not reflect tumoral lymphatic drainage, particularly the para-aortic basins. Although the traditional model for SLN mapping has been peritumoral injection, there is evidence for other tumors, such as periareolar injection in breast cancer, that using a remote site for tracer injection may be equally valid and more feasible.15 * 2013 IGCS and ESGO




FIGURE 3. Outcomes of SLN mapping. A, Cervical injections. B, Hysteroscopic injections. Advocates of the cervical injection site for endometrial cancer argue that the anatomic distributions of SLNs are equivalent to injections of the uterine corpus and are consistent with the most common sites of endometrial cancer lymphatic metastases (internal iliac, external iliac, and obturator nodes).16 Sentinel lymph nodes mapped after cervical dye injections are 3 times more likely to contain metastatic cells than their corresponding lymphadenectomy specimens which suggests that the lymphatic pathways from the cervix

can reproduce the pathway of endometrial cancer metastatic spread.10 However, the greatest advantage of the cervical injection is its feasibility as no separate surgical procedure is required. Our results support the use of cervical injections for SLN mapping in endometrial cancer. There was a significant improvement in detection rate with cervical injection (82% vs 33%) with similar rates of bilaterally identified nodes (57% vs 50%). An explanation for the inferior detection rate after



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hysteroscopic injection group was spillage of dye into the peritoneal cavity, likely a result of inadvertent transmural injection. Once the fluorescent dye entered the peritoneal space, it formed a fluorescent coating of all peritoneal surfaces, making it not possible to identify SLNs due to background staining. The learning curve for hysteroscopic injection may be prolonged compared to the cervical injection group, as we did not see an improvement in detection over time. A single surgeon who had equal experience in the cervical and hysteroscopic injection techniques performed all surgical procedures. Therefore, the improved detection rate from cervical injection cannot be attributed to prior experience. An alternative explanation for the decreased detection rate with hysteroscopic injection is the lower ICG dose used for this cohort. The doses used in this study were based on preclinical animal laboratory data. Our results add to the paucity of published comparative studies of the 2 injection sites for mapping SLNs in endometrial cancer. The question of cervical versus endometrial injection has been described using radiocolloid injections.17 In that particular series, 54 subjects were randomly assigned to receive radiocolloid cervical or hysteroscopic injections followed by laparoscopic endometrial cancer staging procedures. Nearly 30% of patients in the hysteroscopic arm refused to undergo the procedure, suggesting a poor patient acceptability of the hysteroscopic procedure. No significant difference in SLN detection was detected (69.9% vs 64.7%), although these were overall low detection rates, and may reflect learning curve challenges with laparoscopic F probe detection. The study’s authors suggested superiority of the hysteroscopic injection technique due to a nonsignificant increase in the number of para-aortic nodes detected. The incidence of metastatic disease to the para-aortic nodes is approximately 8% to 10%18,19 and is isolated to the paraaortic basins in between 1.6% and 3.2% of patients20,21 depending on the tumor grade. Many feel that SLN mapping techniques for endometrial cancer should include evaluation of the para-aortic nodes. Unlike the previous study, our series found no difference in the anatomic distribution of SLNs seen for the 2 injection sites. Nodes were predominantly mapped in the pelvic basins, particularly internal iliac and obturator regions. However, para-aortic nodes were identified in 72% of patients. This is a higher number than traditional SLN mapping techniques (5%Y18%).10,14,17 Most (85%) of the para-aortic SLNs seen were upper echelon nodes mapped upstream from pelvic SLNs, with the exception of 2 patients (1 from each cohort) in whom isolated para-aortic SLNs were identified. The increased detection of para-aortic SLNs in our study might be explained by the high rate of para-aortic node dissection (83%). The para-aortic basins were routinely opened and explored for fluorescent signal in all but 5 patients. An alternative explanation for the increased para-aortic node detection is the imaging modality used: NIR imaging of fluorescent dyes. The molecular properties of ICG may permit migration of dye from pelvic to the upper echelon nodes while preserving its signal in the original nodes, as evidenced by the fact that para-aortic nodes were, with the exception of

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2 cases, mapped as upper echelon nodes to pelvic SLNs. Additionally, the fluorescent signal from ICG dye can penetrate 5 mm of tissue which may have contributed to our improved visual detection of para-aortic nodes without extensive tissue dissection. The feasibility of SLN mapping with fluorescent imaging and ICG has been described in several cancers including breast, melanoma, rectal, and gastric.22Y25 It has also been described in cervical cancer performed via laparotomy using open NIR imagers such as the photodynamic eye (Hamamatsu Photonics Co).4 These studies measured comparable detection rates for SLNs and metastatic disease when compared to traditional modalities. We have previously described the use of endoscopic and robotic assisted NIR imagers for SLN mapping in cervical and endometrial cancer as a feasible technique, which offers comparable detection rates to those reported with blue dyes and radiocolloids.3 This study represents one of the largest series of patients with endometrial cancer to have SLNs mapped with robotic assisted NIR fluorescence imaging. NIR imagers are not as widely available as the tools used for traditional nodal mapping. Although this currently limits the widespread adoption of this technique, we believe there is still benefit in exploring alternative modalities for SLN mapping and provide options for different surgical approaches, namely, laparotomy, laparoscopy, or robotic. This was a preliminary study exploring the optimization of a novel SLN mapping technique for endometrial cancer. No conclusions can be made regarding the sensitivity of this technique in detecting metastatic disease. Small sample size and only 4 patients with stage IIIC disease limit our analysis. The false-negative result was seen in the first patient in the study. Her single left-sided pelvic SLN was negative, despite positive non-sentinel lymph nodes in the right pelvis. This may be a learning curve phenomenon. It supports the concepts that SLN sampling should not replace complete lymphadenectomy during a surgeon’s learning curve, and that if a SLN is not identified in 1 hemipelvis, a completion lymphadenectomy should be performed on that side.10 In conclusion, cervical injection of ICG followed by robotic assisted NIR imaging to map SLNs in endometrial cancer has comparable SLN detection rates compared to traditional modalities and justifies performing studies with larger patient and surgeon numbers. Cervical dye injections offer superior SLN detection rates to hysteroscopic injections with comparable anatomic nodal distributions that are representative of endometrial cancer nodal metastases.

REFERENCES 1. Kang S, Yoo HJ, Hwang JH, et al. Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies. Gynecol Oncol. 2011;123:522Y527. 2. Khoury-Collado F, Glaser GE, Zivanovic O, et al. Improving sentinel lymph node detection rates in endometrial cancer: how many cases are needed? Gynecol Oncol. 2009;115:453Y455. 3. Rossi EC, Ivanova A, Boggess JF. Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study. Gynecol Oncol. 2012;124:78Y82. * 2013 IGCS and ESGO




4. Furukawa N, Oi H, Yoshida S, et al. The usefulness of photodynamic eye for sentinel lymph node identification in patients with cervical cancer. Tumori. 2010;96:936Y940. 5. Crane LM, Themelis G, Buddingh KT, et al. Multispectral real-time fluorescence imaging for intraoperative detection of the sentinel lymph node in gynecologic oncology. J Vis Exp. 2010. 6. Holloway RW, Bravo RA, Rakowski JA, et al. Detection of sentinel lymph nodes in patients with endometrial cancer undergoing robotic-assisted staging: a comparison of colorimetric and fluorescence imaging. Gynecol Oncol. 2012;126:25Y29. 7. Gynecologic Oncology Group: Surgical Procedures Manual. Revised July 2005. 8. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol 2005;106:413Y425. 9. Bernardini MQ, Murphy JK. Issues surrounding lymphadenectomy in the management of endometrial cancer. J Surg Oncol. 2009;99:232Y241. 10. Khoury-Collado F, Murray MP, Hensley ML, et al. Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes. Gynecol Oncol. 2011;122:251Y254. 11. Wernicke AG, Shamis M, Sidhu KK, et al. Complication rates in patients with negative axillary nodes 10 years after local breast radiotherapy after either sentinel lymph node dissection or axillary clearance. Am J Clin Oncol. 2011;36(1):12Y9. 12. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer. 2006;106:4Y16. 13. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307Y1317. 14. Ballester M, Dubernard G, Lecuru F, et al. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO). Lancet Oncol. 2011;12(5):469Y76.

15. Kern KA. Concordance and validation study of sentinel lymph node biopsy for breast cancer using subareolar injection of blue dye and technetium 99m sulfur colloid. J Am Coll Surg. 2002;195:467Y475. 16. Abu-Rustum NR, Khoury-Collado F, Pandit-Taskar N, et al. Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma? Gynecol Oncol. 2009;113:163Y169. 17. Perrone AM, Casadio P, Formelli G, et al. Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer. Gynecol Oncol. 2008;111:62Y67. 18. Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987;60(suppl 8): 2035Y2041. 19. Ayhan A, Yarali H, Urman B, et al. Lymph node metastasis in early endometrium cancer. Aust N Z J Obstet Gynaecol. 1989;29(3 Pt 2):332Y335. 20. Abu-Rustum NR, Gomez JD, Alektiar KM, et al. The incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes. Gynecol Oncol. 2009;115:236Y238. 21. Mariani A, Dowdy SC, Cliby WA, et al. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol 2008;109:11Y18. 22. Polom K, Murawa D, Nowaczyk P, et al. Breast cancer sentinel lymph node mapping using near infrared guided indocyanine green and indocyanine green-human serum albumin in comparison with gamma emitting radioactive colloid tracer. Eur J Surg Oncol. 2012;38:137Y142. 23. Fujiwara M, Mizukami T, Suzuki A, et al. Sentinel lymph node detection in skin cancer patients using real-time fluorescence navigation with indocyanine green: preliminary experience. J Plast Reconstr Aesthet Surg. 2009;62:e373Ye378. 24. Hirche C, Mohr Z, Kneif S, et al. Ultrastaging of colon cancer by sentinel node biopsy using fluorescence navigation with indocyanine green. Int J Colorectal Dis. 2011;27(3):319Y24. 25. Tajima Y, Murakami M, Yamazaki K, et al. Sentinel node mapping guided by indocyanine green fluorescence imaging in gastric cancer. Ann Surg. 2009;249(1):58Y62



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Sentinel lymph node detection in endometrial cancer: hysteroscopic peritumoral versus cervical injection.

Sentinel node mapping using hysteroscopic injection of indocyanine green and laparoscopic near-infrared fluorescence imaging in endometrial cancer staging.

Robotic-assisted dissection of bulky lymph nodes in cervical cancer.

Sentinel node detection in endometrial cancer using indocyanine green and fluorescence imaging-a case report.

A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer.

Laparoscopic sentinel lymph node mapping after cervical injection of indocyanine green for endometrial cancer - preliminary report.

Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus Laparoscopic Hysterectomy for Endometrial Cancer Staging.

Imaging sentinel lymph nodes.

Intraoperative fluorescence imaging to localize tumors and sentinel lymph nodes in rectal cancer.

Sentinel Lymph Nodes Mapping in Cervical Cancer a Comprehensive Review.

Sentinel lymph node detection in endometrial cancer: does injection site make a difference?

Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies.

Intraoperative Fluorescence Imaging for Sentinel Lymph Node Detection: Prospective Clinical Trial to Compare the Usefulness of Indocyanine Green vs Technetium Tc 99m for Identification of Sentinel Lymph Nodes.

Hydrothorax after robotic-assisted surgical staging of endometrial cancer.

[Hysteroscopic morcellation versus bipolar resection for endometrial polyp removal].

Meta-analysis of superficial versus deep injection of radioactive tracer and blue dye for lymphatic mapping and detection of sentinel lymph nodes in breast cancer.

Robotic-assisted fluorescence sentinel lymph node mapping using multimodal image guidance in an animal model.

Pre-prostatic tissue removed in robotic assisted lymph node dissection for prostate cancer contains lymph nodes.

Incorporating robotic-assisted surgery for endometrial cancer staging: Analysis of morbidity and costs.

Single site robotic sentinel lymph node biopsy and hysterectomy in endometrial cancer.

Robotic single site versus robotic multiport hysterectomy in early endometrial cancer: a case control study.

Laparoscopy-assisted endoscopic full-thickness resection with basin lymphadenectomy based on sentinel lymph nodes for early gastric cancer.

Overall care cost comparison between robotic and laparoscopic surgery for endometrial and cervical cancer.

CT Versus Planar Lymphoscintigraphy for Preoperative Sentinel Lymph Node Detection in Cervical Cancer: A Systematic Review and Metaanalysis.