Instruments and Techniques
Sentinel Node Mapping Using Hysteroscopic Injection of Indocyanine Green and Laparoscopic Near-Infrared Fluorescence Imaging in Endometrial Cancer Staging Antonino Ditto, MD*, Fabio Martinelli, MD, Giorgio Bogani, MD, Andrea Papadia, MD, Domenica Lorusso, MD, and Francesco Raspagliesi, MD From the Gynecologic Oncology Unit, National Cancer Institute, Milan, Italy (all authors).
ABSTRACT Herein is presented a technique for minimally invasive sentinel node mapping. The patient had apparently early stage endometrial cancer. Sentinel node mapping was performed using a hysteroscopic injection of indocyanine green followed by laparoscopic sentinel node detection via near-infrared fluorescence. This technique ensures delineation of lymphatic drainage from the tumor area, thus achieving accurate detection of sentinel nodes. Journal of Minimally Invasive Gynecology (2015) 22, 132–133 Ó 2015 AAGL. All rights reserved. Keywords:
DISCUSS
Endometrial cancer; Fluorescence; Laparoscopy; Lymph node mapping; Sentinel node biopsy
You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-22-2-JMIG-D-14-00371
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Lymphadectomy is the most debated issue in endometrial cancer management [1–3]. Although no mature data have demonstrated the efficacy of lymphadenectomy in improving survival outcomes of early stage endometrial cancer, lymphadenectomy provides important information for tailoring adjuvant therapy, thus reducing the morbidity of unnecessary treatments [1]. In addition, the staging procedures are paramount, in particular in light of lack of reliable noninvasive predictors of extrauterine spread [4]. However, compared with hysterectomy alone, systematic lymphadenectomy is associated with longer operative time and potentially increased surgery-related morbidity [1–3]. Thus, sentinel node biopsy represents a compromise between performance and omission of lymphadenectomy. Sentinel node biopsy provides information about nodal status without performance of systematic retroperitoneal staging procedures. Several investigations have demonstrated Disclosures: None declared. Corresponding author: Antonino Ditto, MD, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. E-mail: [email protected] Submitted July 23, 2014. Accepted for publication August 12, 2014. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2015 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2014.08.009
the overall satisfactory efficacy and effectiveness of sentinel node biopsy in endometrial and cervical carcinomas [5–9]. Several techniques for sentinel node biopsy have been described [5–11]. As previously reported, we have started a policy of systematic implementation of sentinel node biopsy using peritumoral dye injection, thus achieving accurate delineation of the tumor lymphatic drainage [10,11]. Herein we present our standardized technique for sentinel node biopsy using hysteroscopic injection of indocyanine green and fluorescence imaging. Case Report A 68-year-old nulliparous woman with a preoperative diagnosis of FIGO grade 2 endometrioid endometrial cancer was referred to our institution. Her medical history was noteworthy for World Health Organization class I obesity (body mass index, 30.2). A preoperative computed tomography scan was negative for the presence of gross intraabdominal disease. General endotracheal anesthesia was administered. After creation of 15 mm Hg pneumoperitoneum using a Veress needle inserted in the umbilicus, one 10-mm trocar was inserted transumbilically. Under direct visualization, three 5-mm ancillary trocars were inserted in
Ditto et al.
Sentinel Node Mapping Using Indocyanine Green
the abdomen, 1 suprapubically and 2 laterally to the epigastric arteries, in the left and right lower abdominal quadrants, respectively. Although no mature evidence supports the theory that execution of intrauterine procedures provides spillage of tumor cells from the endometrium to the peritoneal cavity, we coagulated the fallopian tubes before proceeding with performance of intrauterine procedures. Hysteroscopy was performed using an operative 4-mm hysteroscope (Richard Wolf GmbH, Knittlingen, Germany). A 22-gauge, 40-mm needle was introduced into the operative port, and 5 mg indocyanine green was injected peritumorally, as previously described [9]. Laparoscopic inspection was performed using a laparoscopic fluorescence imaging system (Karl Storz Endoskope GmbH &Co. KG, Tuttlingen, Germany). Delineation of the course of lymphatic vessels was observed using the near-infrared fluorescence mode of the laparoscope. After the retroperitoneum was opened, a right-side obturator sentinel node was identified and removed. No left-side fluorescent node was detected. Hysterectomy and bilateral salpingo-oophorectomy were performed. Frozen section analysis demonstrated a negative pelvic node and FIGO grade 1 endometrioid endometrial cancer confined in the inner half of the myometrium. No complications occurred, and the patient was discharged on the first postoperative day. Video 1 shows hysteroscopic injection of indocyanine green and sentinel node detection. Discussion In our practice, sentinel node biopsy is not performed in patients with high-risk endometrial cancer (FIGO grades 2 and 3 endometrioid endometrial cancer with deep myometrial invasion and non-endometrioid endometrial cancer) because this subgroup of patients is at high risk for lymph node metastases in the para-aortic area and skip lesions (negative pelvic and positive para-aortic nodes) [1]. In addition, systematic lymphadenectomy is performed in patients with enlarged nodes detected at preoperative imaging (in general, nodes .1 cm detected using computed tomography) and in those with positive nodes detected at frozen section analysis. In conclusion, we have presented our technique for sentinel node mapping using intraoperative hysteroscopic injection of indocyanine green followed by near-infrared fluorescence imaging. Although growing evidence suggests that cervical injection is effective in enabling detection of lymphatic drainage from the uterus, hysteroscopy enables injection in the proximity of the neoplastic lesions. In addition, near-infrared fluorescence imaging is effective for clear
133
delineation of peritumoral lymphatic drainage. Advantages of using indocyanine green include independence from nuclear medicine, and disadvantages include dedicated camera-related costs. Further prospective studies are warranted to assess the learning curve, optimal concentration of indocyanine green, site of injection (submucosal vs intramyometrial), and ideal timing between injection and node detection.
Supplementary Data Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.jmig.2014.08.009. References 1. Bogani G, Dowdy SC, Cliby WA, Ghezzi F, Rossetti D, Mariani A. Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: current evidence. J Obstet Gynaecol Res. 2014;40:301–311. 2. Benedetti Panici P, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial cancer: randomized clinical trial. J Natl Cancer Inst. 2008;100: 1707–1716. 3. ASTEC Study Group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009;373:125–136. 4. Angioli R, Miranda A, Aloisi A, et al. A critical review on HE4 performance in endometrial cancer: where are we now? Tumour Biol. 2014; 35:881–887. 5. Frumovitz M, Ramirez PT, Levenback C. Lymphatic mapping and sentinel node detection in gynecologic malignancies of the lower genital tract. Curr Oncol Rep. 2005;7:435–443. 6. Frumovitz M, Coleman RC, Soliman PT, Ramirez PT, Levenback CF. A case for caution in the pursuit of the sentinel node in women with endometrial carcinoma. Gynecol Oncol. 2014;132:275–279. 7. Rossi EC, Jackson A, Ivanova A, Boggess JF. Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection. Int J Gynecol Cancer. 2013;23: 1704–1711. 8. Kim CH, Khoury-Collado F, Barber EL, et al. Sentinel lymph node mapping with pathologic ultrastaging: a valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion. Gynecol Oncol. 2013;131:714–719. 9. Leitao MM Jr, Khoury-Collado F, Gardner G, et al. Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer. Gynecol Oncol. 2013;129:38–41. 10. Raspagliesi F, Ditto A, Kusamura S, et al. Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study. Am J Obstet Gynecol. 2004;191:435–439. 11. Solima E, Martinelli F, Ditto A, et al. Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer. Gynecol Oncol. 2012;126:419–423.
Sentinel Node Mapping Using Hysteroscopic Injection of Indocyanine Green and Laparoscopic Near-Infrared Fluorescence Imaging in Endometrial Cancer Staging Antonino Ditto, MD*, Fabio Martinelli, MD, Giorgio Bogani, MD, Andrea Papadia, MD, Domenica Lorusso, MD, and Francesco Raspagliesi, MD From the Gynecologic Oncology Unit, National Cancer Institute, Milan, Italy (all authors).
ABSTRACT Herein is presented a technique for minimally invasive sentinel node mapping. The patient had apparently early stage endometrial cancer. Sentinel node mapping was performed using a hysteroscopic injection of indocyanine green followed by laparoscopic sentinel node detection via near-infrared fluorescence. This technique ensures delineation of lymphatic drainage from the tumor area, thus achieving accurate detection of sentinel nodes. Journal of Minimally Invasive Gynecology (2015) 22, 132–133 Ó 2015 AAGL. All rights reserved. Keywords:
DISCUSS
Endometrial cancer; Fluorescence; Laparoscopy; Lymph node mapping; Sentinel node biopsy
You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-22-2-JMIG-D-14-00371
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Lymphadectomy is the most debated issue in endometrial cancer management [1–3]. Although no mature data have demonstrated the efficacy of lymphadenectomy in improving survival outcomes of early stage endometrial cancer, lymphadenectomy provides important information for tailoring adjuvant therapy, thus reducing the morbidity of unnecessary treatments [1]. In addition, the staging procedures are paramount, in particular in light of lack of reliable noninvasive predictors of extrauterine spread [4]. However, compared with hysterectomy alone, systematic lymphadenectomy is associated with longer operative time and potentially increased surgery-related morbidity [1–3]. Thus, sentinel node biopsy represents a compromise between performance and omission of lymphadenectomy. Sentinel node biopsy provides information about nodal status without performance of systematic retroperitoneal staging procedures. Several investigations have demonstrated Disclosures: None declared. Corresponding author: Antonino Ditto, MD, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. E-mail: [email protected] Submitted July 23, 2014. Accepted for publication August 12, 2014. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2015 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2014.08.009
the overall satisfactory efficacy and effectiveness of sentinel node biopsy in endometrial and cervical carcinomas [5–9]. Several techniques for sentinel node biopsy have been described [5–11]. As previously reported, we have started a policy of systematic implementation of sentinel node biopsy using peritumoral dye injection, thus achieving accurate delineation of the tumor lymphatic drainage [10,11]. Herein we present our standardized technique for sentinel node biopsy using hysteroscopic injection of indocyanine green and fluorescence imaging. Case Report A 68-year-old nulliparous woman with a preoperative diagnosis of FIGO grade 2 endometrioid endometrial cancer was referred to our institution. Her medical history was noteworthy for World Health Organization class I obesity (body mass index, 30.2). A preoperative computed tomography scan was negative for the presence of gross intraabdominal disease. General endotracheal anesthesia was administered. After creation of 15 mm Hg pneumoperitoneum using a Veress needle inserted in the umbilicus, one 10-mm trocar was inserted transumbilically. Under direct visualization, three 5-mm ancillary trocars were inserted in
Ditto et al.
Sentinel Node Mapping Using Indocyanine Green
the abdomen, 1 suprapubically and 2 laterally to the epigastric arteries, in the left and right lower abdominal quadrants, respectively. Although no mature evidence supports the theory that execution of intrauterine procedures provides spillage of tumor cells from the endometrium to the peritoneal cavity, we coagulated the fallopian tubes before proceeding with performance of intrauterine procedures. Hysteroscopy was performed using an operative 4-mm hysteroscope (Richard Wolf GmbH, Knittlingen, Germany). A 22-gauge, 40-mm needle was introduced into the operative port, and 5 mg indocyanine green was injected peritumorally, as previously described [9]. Laparoscopic inspection was performed using a laparoscopic fluorescence imaging system (Karl Storz Endoskope GmbH &Co. KG, Tuttlingen, Germany). Delineation of the course of lymphatic vessels was observed using the near-infrared fluorescence mode of the laparoscope. After the retroperitoneum was opened, a right-side obturator sentinel node was identified and removed. No left-side fluorescent node was detected. Hysterectomy and bilateral salpingo-oophorectomy were performed. Frozen section analysis demonstrated a negative pelvic node and FIGO grade 1 endometrioid endometrial cancer confined in the inner half of the myometrium. No complications occurred, and the patient was discharged on the first postoperative day. Video 1 shows hysteroscopic injection of indocyanine green and sentinel node detection. Discussion In our practice, sentinel node biopsy is not performed in patients with high-risk endometrial cancer (FIGO grades 2 and 3 endometrioid endometrial cancer with deep myometrial invasion and non-endometrioid endometrial cancer) because this subgroup of patients is at high risk for lymph node metastases in the para-aortic area and skip lesions (negative pelvic and positive para-aortic nodes) [1]. In addition, systematic lymphadenectomy is performed in patients with enlarged nodes detected at preoperative imaging (in general, nodes .1 cm detected using computed tomography) and in those with positive nodes detected at frozen section analysis. In conclusion, we have presented our technique for sentinel node mapping using intraoperative hysteroscopic injection of indocyanine green followed by near-infrared fluorescence imaging. Although growing evidence suggests that cervical injection is effective in enabling detection of lymphatic drainage from the uterus, hysteroscopy enables injection in the proximity of the neoplastic lesions. In addition, near-infrared fluorescence imaging is effective for clear
133
delineation of peritumoral lymphatic drainage. Advantages of using indocyanine green include independence from nuclear medicine, and disadvantages include dedicated camera-related costs. Further prospective studies are warranted to assess the learning curve, optimal concentration of indocyanine green, site of injection (submucosal vs intramyometrial), and ideal timing between injection and node detection.
Supplementary Data Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.jmig.2014.08.009. References 1. Bogani G, Dowdy SC, Cliby WA, Ghezzi F, Rossetti D, Mariani A. Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: current evidence. J Obstet Gynaecol Res. 2014;40:301–311. 2. Benedetti Panici P, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial cancer: randomized clinical trial. J Natl Cancer Inst. 2008;100: 1707–1716. 3. ASTEC Study Group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009;373:125–136. 4. Angioli R, Miranda A, Aloisi A, et al. A critical review on HE4 performance in endometrial cancer: where are we now? Tumour Biol. 2014; 35:881–887. 5. Frumovitz M, Ramirez PT, Levenback C. Lymphatic mapping and sentinel node detection in gynecologic malignancies of the lower genital tract. Curr Oncol Rep. 2005;7:435–443. 6. Frumovitz M, Coleman RC, Soliman PT, Ramirez PT, Levenback CF. A case for caution in the pursuit of the sentinel node in women with endometrial carcinoma. Gynecol Oncol. 2014;132:275–279. 7. Rossi EC, Jackson A, Ivanova A, Boggess JF. Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection. Int J Gynecol Cancer. 2013;23: 1704–1711. 8. Kim CH, Khoury-Collado F, Barber EL, et al. Sentinel lymph node mapping with pathologic ultrastaging: a valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion. Gynecol Oncol. 2013;131:714–719. 9. Leitao MM Jr, Khoury-Collado F, Gardner G, et al. Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer. Gynecol Oncol. 2013;129:38–41. 10. Raspagliesi F, Ditto A, Kusamura S, et al. Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study. Am J Obstet Gynecol. 2004;191:435–439. 11. Solima E, Martinelli F, Ditto A, et al. Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer. Gynecol Oncol. 2012;126:419–423.
