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trial cancers in the United States attributable to obesity [4].
Therefore, gynecological surgery for both benign and oncologic
cases will likely continue to grow.
Fluorescence-guided surgery (FGS) is on the forefront of medicine with at least 85 clinical trials in the United States, and numerous applications already implemented across the world [5].
Fluorescence-guided surgery utilizes uorescent dye or a nearinfrared emitting light source to identify anatomic structures during
surgical procedures. This chapter will describe uses of FGS in
gynecologic oncology for lymphatic mapping, sentinel lymph node
identication, and tumor margin detection, and in benign gynecology, for the management of endometriosis and during complex pelvic reconstruction, as well as for improving identication of
anatomical structures and augmenting intraoperative navigation.
L. Lipetskaia et al.
Disease-Specic Applications ofFluorescence
Imaging
Gynecologic Oncology
Tumor Lymphatic Imaging inGynecologic Cancers
Endometrial cancer (EC): Indocynanine Green (ICG) dye is clinically used to monitor the lymphatic vessels and sentinel lymph
nodes (SLN) of uterine tumors [6]. It can reduce lymphedema and
other associated morbidities to selectively remove SLNs which
can prevent tumor metastasis. ICG improved the detection rate of
pelvic SLN compared to conventional dyes and may be considered as the superior technique [7]. In clinical practice, the rate of
systematic LND further decreased after incorporating SLN mapping with ICG. The National Comprehensive Cancer Network
(NCCN) recommends uorescent SLN mapping for endometrial
cancer by cervical ICG injection directly [8]. The NCCN guidelines have approved sentinel node localization as a staging technique for EC, as grade 2B evidence. Prospective and retrospective
clinical studies have shown that sentinel lymph node mapping
(SLNM) combined with pathologic ultra-staging has satisfactory
detection rate, sensitivity, and negative predictive value of SLN in
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patients with early low-risk endometrial carcinoma and does not
affect progression-free and overall survival rates. However, the
prognostic effect of SLN mapping in high-risk EC patients still
needs to be further veried by larger studies. In the earlier version, NCCN guidelines suggested SLN mapping should be cautious for high-risk EC patients. In the latest version, it is believed
that SLN mapping may also have a high detection rate and diagnostic accuracy in high-risk EC.Pelvic/para-aortic sentinel lymph
nodes were three times more likely to be extracted than nonSLNs, providing accurate staging for optimized postoperative
patient management [8]. To date, no published randomized study
has investigated the survival benet. Therefore, although the use
of ICG and uorescent detection cameras is considered the most
appropriate for obtaining the best detection rates in lymphatic
mapping in endometrial cancer, the SLN technique still is considered as experimental (Fig.16.1).
Imaging techniques: 1.25 mg/mL concentration, 4 mL (1 mL
deep and 1mL supercial), was injected into the cervix (3 and 9
o’clock position) with 10 min waiting time before dissection.
Alternatively, ICG can be injected into tumor directly (via hysteroscopy) or fundally/subserosally. The latter approach increases paraaortic LN detection rate but decreases pelvic LN detection rate and
can lead to intraabdominal dispersion of the dye [9] (Fig.16.2).
Cervical cancer: Cervical cancer is not as prevalent as endometrial cancer, and data on SLN mapping is limited and frequently
derived from the studies analyzing SLN detection in cases of cer-
Fig. 16.1 Endometrial cancer: right obturator sentinel lymph node regular
light (left) and infrared light (right)
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Fig. 16.2 High-resolution image of para-aortic sentinel lymph node mapping for endometrial cancer during robotic LND
L. Lipetskaia et al.
vix and endometrial cancer. The assumption is made that migration
to the pelvic nodes is similar in both cancers. With this caveat, the
studies demonstrate the effectiveness of ICG during SLN biopsy
using robotic, laparoscopic surgery and laparotomy, concluding
that the method is feasible, safe, time-efcient, and seemingly
reliable for lymphatic mapping in early-stage cervical cancer
[10]. Two-meta-analyses concluded that in cervical and endometrial cancer, ICG SLN-mapping seems to be equivalent or superior
to the conventional dyes [11, 12].
Imaging technique: No standardized technique was reported.
Concentrations of ICG have ranged from 0.5 to 5.0mg/mL, and
injected volumes have varied from 0.2 to 4.0 mL. The study in
healthy female pigs identied 250–500μg ICG dose as optimal in
identication of a SLN with more distinction from the surrounding tissues [13]. Cervix is injected in 2–4 quadrants (12, 3, 6, and
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9h or 3 and 9). Slow injection is recommended to prevent damage
to lymphatic vessels. Optimal time for starting dissection is
unclear. In the studies, the median time between injection and the
start of dissection is approximately 30min.
Vulvar cancer: In the vulva bilateral SLN sampling should be
assured in central tumors only. If tumor is located at least 1cm
lateral to the clitoris, unilateral dissection is sufcient. A standard
technique for dissection involves the use of double tracer (blue
dye and Tc-99m-labeled radiocolloid) and requires a lymphoscintigraphy. The use of ICG in vulvar cancer is limited as nearinfrared (NIR) uorescence can detect targets up to 5–8mm deep
[14]. A deeper target at 25mm would be invisible by NIR uorescence imaging alone; hence, majority studies combine NIR uorescence imaging with radioscintigraphy which enables
visualization of deeper inguinal SLNs, especially in patients with
obesity. The robotic video endoscopy inguinal lymphadenectomy
is emerging technique for diagnosis of vulvar cancer, but so far
only one case report with SLN mapping with ICG followed by
systematic inguinal lymphadenectomy is described [15]. So far,
the best results in mapping are achieved using a combination of
ICG and technetium-99m nanocolloid. Once overlying tissue is
removed, as guided by radioscintigraphy, NIR uorescence is
used for more precise image guidance to compensate for relatively poor spatial and temporal resolution of radioscintigraphy.
Body mass index seems to be a limitation for using ICG alone as
a tracer.
Imaging technique: Concentration of 0.5/2.5mg/mL.A total
of 4 mL (1 mL at 4 sites) was injected directly into the tumor
(intracutaneously) with dissection starting in 10min. Alternatively,
ICG can be injected around the scar at prior excision site in case
of cancer recurrence.
Ovarian cancer (OC): The incidence of lymph node metastases
in early OC ranges between and 30%, and pelvic and paraaortic
lymphadenectomy is recommended. In early ovarian cancer,
lymph node metastases are found as isolated para-aortic nodes in
50% of patients, as isolated pelvic nodes in 20% of patients, and
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L. Lipetskaia et al.
in both in the remaining 30% of patients [16]. The three major
ovarian lymphatic drainage pathways (infundibulopelvic ligament, the ovarian ligament, and the round ligament) explain the
wide geography of the metastatic disease and point out to the
potential injection sites for tracers. So far, two ongoing prospective, multicenter studies attempt to determine efcacy and safety
of ICG in SLN mapping. Both SELLY (SLN in early-stage ovarian cancer) and SENTOV ((sentinel lymph node technique in
ovarian cancer) evaluate ICG in conjunction with Tc-99m. The
Tc-99m remains trapped in the lymph nodes for a long period and
is injected before the oophorectomy. The small ICG molecule
migrates rapidly through lymphatic vessels and makes it difcult
to accurately identify the rst node; hence, ICG is injected after
an ovary is removed. The preliminary data from SELLY and
SENTOV concluded that SLN mapping in early-stage ovarian
cancer is feasible without major intraoperative or safety concerns
[17] [18]. The data on accuracy and detection rate of this technique is not available yet; hence, no recommendation can be given
because this procedure still is experimental.
Imaging technique: Concentration of 1.25mg/mL.A total of
0.5–1mL was injected into infundibulopelvic and ovarian ligament with dissection starting almost immediately. Alternative
injection sites are mesovarium, hilum of the ovary, and ovarian
cortex.
Tumor Margin Detection
Free surgical margin is the main challenge in vulvar and vaginal
cancer surgery. In solid tumors, incomplete surgery results in high
risk of tumor recurrence. The real-time detection of tumor margins helps achieve complete resection and decrease risk of recurrence. Case reports present ICG use in vulvar and vaginal cancer
for surgical resection guidance. In the rst case after primary
incomplete resection of vulvar cancer, an intravenous ICG injection determined the free margin after resection. In the second
case, peritumoral ICG injection 1 cm around the upper vagina
cancer showed a clear resection margin on the nal pathological
nding after robotic colpo-hysterectomy with LND [19].
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Imaging technique: For vulvar cancer, 2cc of diluted ICG IV
immediately before surgery and for vaginal cancer, 2mL peritumoral injection with 1cm radius. No uterine manipulator is used,
and a vaginal probe is inserted to develop the fornix. Techniques
need to be validated on a large scale.
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Management ofBowel andGU Anastomosis asaPart
ofCytoreductive Surgery
Several patient and surgical factors inuence the risk of anastomotic leak after bowel resection during pelvic exenteration.
Surgeons typically rely on subjective methods to identify anastomotic leaks such as palpation of vessels and assessment of tissue
vitality in white light. The addition of intraoperative ICG assessment of colorectal anastomoses demonstrated reduced risk of
anastomotic leakage in treatment of GI malignancies in ten studies. In seven studies, resection of the colon or rectum was extended
into more vital tissue if ICG detected an insufcient perfusion at
the proposed anastomosis site. Three studies concluded that ICG
perfusion assessment reduced the risk of anastomotic leakage signicantly. One study found no difference in anastomotic leakage
rate between the control group and the ICG group [20]. This concept was adopted in the management of anastomosis in gynecologic cancers requiring wide organ resection as a part of
cytoreduction strategy. ICG was used to evaluate perfusion of
ileum-ileum, right and left ureter with small bowel, and colorectal
sides of anastomosis to assess vascularity of urinary diversion
after pelvic exenteration for gynecologic cancers (Fig.16.3). Out
of 15 subjects, 3 patients had postoperative complications due to
poor perfusion of anastomosis (ureteral and ileal anastomosis
leaks and ureteric stricture); all these cases had a suboptimal
intraoperative ICG perfusion [21] (Fig.16.4).
Imaging technique: IV ICG bolus before and/or after anastomosis construction 0.2–0.5 mg/kg (total ranging from 0.2 to
0.5mg/kg). In order to achieve a more objective perfusion assessment, scoring systems were developed and intraoperative pixel
brightness analysis was performed. Unfortunately, the quantication did not lead to a cutoff value.
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Fig. 16.3 Bricker ileal conduit uretero-enteric anastomoses demonstrating
right ureter with optimal indocyanine green (ICG) perfusion (+++) vs. left
ureter with poor ICG perfusion (− − -). (Bizzai etal. Indocyanine Green to
Assess Vascularity of Ileal Conduit Anastomosis During Pelvic Exenteration
for Recuent/Persistent Gynecological Cancer: A Pilot Study. Front Oncol.
2021 Dec 7;11:727725. doi: 10.3389/fonc.2021.727725. PMID: 34950574;
PMCID: PMC8691262)
L. Lipetskaia et al.
Surgical Management ofEndometriosis
Detection ofEndometriotic Lesions
Endometriosis has three clinical forms: peritoneal supercial
endometriosis, ovarian endometriosis and deeply inltrating
endometriosis in the rectovaginal septum [22]. Identifying endometriosis lesions may be challenging due to variable appearances,
small size, and concealed localization. ICG green highlights the
location of endometriotic lesions as they are associated with
increased areas of vascularization and inammation. The endometriotic lesion patterns observed during surgery are described as
diffuse or abundant uorescence (hypervascular pattern) in 40%
women and poor or absent (hypovascular pattern) in 60% women
with endometriosis. Although some studies report excellent sensi-
ab
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Fig. 16.4 Transabdominal anastomotic perfusion assessment using the SPYPHI system (Stryker, USA). (a) Transabdominal perfusion assessment showing well-perfused bowel. (b) Transabdominal perfusion assessment showing
perfusion defect (Nguyen JMV etal. The use of indocyanine green uores-
cence angiography to assess anastomotic perfusion following bowel resection in surgery for gynecologic malignancies– A report of 100 consecutive
anastomoses. Gynecol Oncol. 2020 Aug;158 (2):402–406. Doi: 10.1016/j.
ygyno.2020.05.008. Epub 2020 May 15. PMID: 32423604)
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tivity and specicity in identifying the lesions, others conclude
that the single use of ICG shows no improvement in the detection
of endometriosis [22]. It appears that ICG performs better in providing demarcation of deep endometriotic lesions assisting with
more complete resection, but its diagnostic value is controversial.
Imaging technique: 0.25 mg/kg ICG i.v. with time intervals
varying between a minimum of 5 and a maximum of about 30min.
Management ofBowel Involvement During Surgery
forEndometriosis
ICG green is used to evaluate the bowel vascularization after
endometriosis rectal shaving surgery. Separating the healthy rectal tissue from the rectovaginal deep nodules aids in decision
whether to enlarge the resection to the posterior vaginal fornix
[23]. Deep lesion excision and rectal shaving techniques required
for successful endometriosis treatment can jeopardize rectal wall
integrity and lead to rectovaginal stula formation. Visual assessment of the rectal shaving area is labeled as uoresced with the
visual Likert-type scale. Oversewing of rectal muscularis is performed if there is a concern for rectal tissue integrity (Fig.16.5).
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Fig. 16.5 Coagulated tissue appears dark and non-perfused in the area where
rectal shaving was performed (Bar-Shavit Y, etall Use of indocyanine green
in endometriosis surgery. Fertil Steril. 2018 Jun;109 (6):1136–1137. doi:
10.1016/j.fertnstert.2018.02.113. Epub 2018 Jun 6. PMID: 29885885)
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The RCT study is underway to assess if this technique leads to
decrease stula formation [24]. Another study demonstrated that
when full-thickness bowel resection is necessary for nodule excision, ICG perfusion mapping can be performed in the same manner as in colorectal surgery [25].
Imaging technique: A IV bolus of 0.2mg/kg of indocyanine
green after dilution (2.5mg/mL) at the end of a rectal shaving.
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Complex Pelvic Reconstructive Procedures
Demarcating Retropubic Space Anatomy inBurch
Colposuspension
Retropubic colposuspension is a surgical treatment which involves
lifting the tissues near the bladder neck and proximal urethra and
attaching them to Cooper’s ligament in attempt to treat stress urinary incontinence. Procedure is traditionally performed via open
approach and tension of the sutures attaching vagina to Cooper’s
ligament adjusted by palpation. With advent of robotic surgery
and lack of haptic feedback, new methods of tension adjustment
are needed. Bladder neck can be identied by tagging on Foley
balloon inserted into the bladder and inated with 30cc of ICG
tinged medium. Foley balloon highlighted by ICG demarcates
bladder wall from underlying vaginal tissue plain allowing for
more precise dissection and adequate suspension suture.
Imaging technique: 100cc of intralipid TPN solution mixed
with 0.5 mL of ICG green (2.5 mg/mL in distilled water) and
30cc instilled in 18F Foley balloon inserted into the bladder [26].
Neovagina Construction inCongenital Anomalies
andTransgender Surgery
Patients with vaginal agenesis undergo vaginoplasty using a mold
that had been wrapped with skin graft (McIndoe technique) or
external traction device placed over the abdominal wall (Vecchietti
procedure). Trans-female patients might require laparoscopic sigmoid vaginoplasty if standard penile-scrotal ap inversion technique is not feasible. In either case, creation of neovagina is a
highly complex surgery requiring meticulous dissection of com-
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