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12 Use ofFluorescence Guidance inPediatric Surgery
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intraoperatively by palpation [22]. ICG also demonstrates effectiveness for relapsed hepatoblastoma, including patients who previously underwent liver transplantation for management of
hepatoblastoma and subsequently presented with relapse in the
liver graft [55].
The high sensitivity and seamless integration into robotic or
laparoscopic cameras make ICG a useful adjunct during both
open and laparoscopic resections in children. It is particularly
useful for laparoscopic-assisted oncologic resections, during
which palpation of the liver surface is less feasible [52].
ICG can also be used to evaluate hepatic perfusion and delineate boundaries between liver segments during hepatectomy.
Terasawa etal. developed a technique that would allow for assessment of the boundaries of tumor-bearing hepatic segments, both
to determine a line of transection and to evaluate the perfusion of
the preserved hepatic parenchyma [56]. After transecting the
hepatic parenchyma and clamping the portal pedicle of the tumorbearing hepatic segments, 1.25mg of ICG is administered intravenously. This creates a visual line of demarcation between
non-uorescing tumor-bearing hepatic segments that are to be
resected and surrounding uorescing hepatic parenchyma to be
preserved.
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Non-hepatic Primary Tumor Resection
Until recently, most reports of uorescent-guided resection of
non-hepatic primary tumors were limited to case reports and
series of adult patients. However, recent series have demonstrated
the successful utilization of ICG as an adjunct during oncologic
resection of non-hepatic tumors in children. Furthermore, prospective trials assessing the feasibility of ICG-mediated nearinfrared imaging for resection and identication of margins in
pediatric neoplasms are currently underway.
Esposito et al. utilized ICG for laparoscopic excision of
abdominal lymphoma and robot-assisted resection of ovarian
tumors in pediatric patients [12]. ICG was administered intravenously at a dosage of 0.5mg/mL/kg for three patients with lym-

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S. Scholz et al.
phoma. ICG allowed for assessment of the vascularization of the
lymphoma tumor, helped dene the level of resection in cases
requiring mesenteric division, and was used to detect lymph nodes
for biopsy or resection. Of the ve patients with ovarian tumors,
three were mature teratomas and two were seromucinous cystadenoma on pathology. Patients received an intravenous administration of ICG at a dosage of 0.5 mg/mL/kg. Within 20–30s of
injection, ICG allowed for delineation between the hypouorescent ovarian tumor and normal salpinx and ovarian parenchyma. It also allowed for verication of perfusion to the salpinx
and uterus following tumor resection.
In a large series of pediatric patients, Abdelhafeez et al.
achieved uorescence in 46 out of 52 tumors: nine osteosarcomas, six neuroblastomas, six non-rhabdomyosarcoma soft tissue
sarcomas, ve rhabdomyosarcomas, three Ewing sarcomas, two
germ cell tumors, one chondroblastoma, one solid pseudopapillary neoplasm of the pancreas, one lymphoma, and one myoepithelial carcinoma of the chest wall (in addition to nine
hepatoblastomas and two hepatocellular carcinomas) [51]. The
majority of patients received 1.5 mg/kg of ICG intravenously
over 15min the day prior to surgery. Near-infrared imaging demonstrated an 88% sensitivity and 77% specicity rate for identifying tumors. Eighty- eight percent of malignant tumors
demonstrated uorescence versus 23% of benign lesions. ICG
was unable to identify two primary adrenocortical tumors
included in this series.
Background noise from ICG uptake of surrounding organs is a
common concern in uorescence-guided surgery. Abdelhafeez
etal. reported that background noise was observed in 57% of procedures, including 100% of trunk and extremity resections, 68%
of abdominal operations, and 40% of thoracic cases [51]. Of note,
although background noise from adjacent organs was noted in all
open abdominal and thoracic operations, it was only seen in 45%
and 15% of minimally invasive abdominal and thoracic resections, respectively. This suggests that optimization of ambient
light contamination may be a strategy for mitigating the effects of
background noise during ICG-guided resections.

12 Use ofFluorescence Guidance inPediatric Surgery
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Future investigations are warranted for several areas pertaining
to uorescent-guided pediatric surgical oncology, including methods for mitigating background noise, evaluation of the efcacy of
ICG-guided surgery for organ-sparing operations in cases such as
bilateral Wilms tumors, optimizing identication of neuroblastoma
and sarcoma metastases, and margin delineation inlocal control
operations for neuroblastoma and sarcomas.
363
Pulmonary Metastasectomy forPrimary Hepatic
Tumors
Because ICG does not typically collect in normal lung tissue and
metastatic lesions are commonly found in the periphery of the
lung, ICG uorescence allows for detection of very small, nonpalpable pulmonary metastases secondary to hepatic malignancies
[21]. ICG is concentrated in hepatocytes and metastases from
hepatic tumors, making it a benecial adjunct for metastasectomy
procedures [53]. The use of ICG for pulmonary metastasectomy
via thoracotomy or thoracoscopy has been documented for both
hepatoblastoma and hepatocellular carcinomas in pediatric patients
[17]. It can detect pulmonary lesions as small as 0.062 mm in
diameter [50]. A dose of 0.5mg/kg of ICG administered approximately 24h prior to surgery is generally recommended [57].
ICG is particularly helpful for thoracoscopic identication of
metastatic lesions, where palpation is less feasible and the
decrease in ambient light minimizes background noise compared
to open resections [53]. Single lung ventilation with collapse of
the affected lung should be utilized when medically feasible to
enhance detection of lesions with ICG [21]. Given that ICG has
less optimal penetration for lesions more than 10mm below the
surface of the lung, a secondary localization technique should be
considered for deeper lesions [19]. To optimize detection of nodules, contrast mode, which demonstrates ICG signal over a dark
background, can be used initially [53]. This is followed by overlay mode, which demonstrates ICG signal over the white light
image of the lung, to guide wedge resection (Fig.12.6).

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Fig. 12.6 A 2-year-old girl with PRETEXT III metastatic hepatoblastoma to
the lung s/p cycle 3 chemotherapy and 3 left and 2 right pulmonary nodules.
Therapeutic goal was to reach eligibility for liver transplant. Lung mets were
easily identied with ICG and thoracoscopic SPY technology and removed
with clear margins by wedge resection (lower picture). Note that ICG has to be
given at 0.5mg/kg 24h in advance to the procedure. SPY technology allows
thoracoscopic detection and parenchymal-sparing complete resection (Images
courtesy of Drs. Densmore and Mowrer, Children’s Hospital of Wisconsin)

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365
Pulmonary Metastasectomy forNon-hepatic
Tumors
ICG is also being increasingly used for pulmonary and pleural
metastasectomy via thoracotomy or thoracoscopy for pediatric
tumors of non-hepatic primary. Its use has been documented for
pulmonary metastases secondary to nephroblastoma, neuroblastoma, chondroblastoma, and numerous sarcomas, including
osteosarcoma, Ewing sarcoma, non-rhabdomyosarcoma soft tissue sarcoma, and rhabdomyosarcoma [57]. The surgical principles are similar to those for pulmonary metastasectomy for hepatic
primary tumors.
In comparison to metastases secondary to hepatic primary
tumors, metastases of non-hepatic primary tumors may require
higher doses of ICG for optimal uorescence (e.g., 3–4mg/kg).
ICG dosages up to 5 mg/kg administered approximately 24 h
prior to surgery have been reported [58]. Although this is higher
than the dosage currently approved by the US Food and Drug
Administration (FDA), adverse events related to ICG administration are rare [5]. A higher concentration of ICG can be used (i.e.,
5mg/mL instead of 2.5 mg/mL) to decrease the volume of ICG
injected [53].
In a series of 52 adult patients with a history of sarcoma who
underwent pulmonary metastasectomy, additional lesions were
detected with ICG in 59% of patients in the uorescence-guided
surgery cohort versus 25% of patients in the historical control
cohort for whom additional lesions were detected with visual and
tactile feedback alone (p < 0.05). Patients in the uorescenceguided surgery group also had signicantly improved median
progression-free survival and longer time to recurrence in the lung
compared to historical controls [58].
Further investigation is warranted to evaluate the effect of
treatment necrosis and decreased tumor viability on ICG sensitivity of pulmonary nodules. However, ICG is a promising adjunct
for pulmonary metastasectomy.

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Lymph Node Identication andSentinel Lymph
Node Biopsy
Sentinel lymph node biopsy (SLNB) is an important technique for
staging and regional lymph node assessment of malignancy
(Figs.12.7 and 12.8). Although well established for many types of
Fig. 12.7 ICG lymphangiography for sentinel lymph node biopsy for melanoma of the left ear using the SPY Portable Handheld Imaging System. The
upper image shows the overlay mode and the lower image the SPY uorescence mode. ICG is injected into the lesion on the upper ear. Note clear visibility of the lymph vessels leading to the sentinel node of the lesion (Images
courtesy of Dr. Marcus Malek, UPMC Children’s Hospital of Pittsburgh)

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367
Fig. 12.8 ICG lymphangiography for sentinel lymph node biopsy for melanoma of the right upper thigh using the SPY Portable Handheld Imaging System. The upper image shows the overlay mode and the lower image the SPY
uorescence mode. ICG is injected into the lesion on the upper thigh. Note
clear visibility of the lymph vessels leading to the sentinel node of the lesion.
The right lower image shows the uorescence of the resected sentinel lymph
node (Images courtesy of Dr. Marcus Malek, UPMC Children’s Hospital of
Pittsburgh)

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adult cancer, the role for SLNB in pediatric cancers is less dened
[59]. SLNB is currently used in pediatric cases of melanoma and
various sarcomas, including rhabdomyosarcoma and certain soft
tissue sarcomas [59]. Technetium lymphoscintigraphy remains
the gold standard for SLNB, with blue dyes such as lymphazurin
or methylene blue often used in conjunction for visual identication of sentinel nodes. Valente et al. found that ICG with NIR
uorescence imaging was safe and performed similarly to technetium 99m for SLNB in breast cancer patients [60]. ICG has also
been used for SLNB and lymph node harvest in other adult cancer
types, including melanoma, gynecologic cancers, and colorectal
cancers [61–63]. It is currently unknown whether uorescent or
ICG lymphoscintigraphy is noninferior for SLNB or lymph node
identication in pediatric patients. However, it can be used an
adjunct for lymph node identication [12].
In pediatric patients, reports of ICG use for lymph node identication and SLNB have been more limited. Esposito etal. utilized
ICG to detect a thoracic hilar lymph node for biopsy for suspected
lymphoma [14]. A 0.5mg/mL/kg of ICG was injected into the
lung parenchyma intraoperatively to assist with lymph node identication [12]. In a series of pediatric patients with paratesticular
rhabdomyosarcoma, Manseld etal. injected 10mg of ICG into
the spermatic cord under either direct visualization or ultrasound
guidance to facilitate retroperitoneal lymph node dissection [64].
Injection of ICG into the spermatic cord led to iliac lymph node
avidity using near-infrared spectroscopy, with sequential spread
along the ipsilateral para-aortic or para-caval lymph node chain.
Recently, a case report described the use of ICG to increase lymph
node harvest during laparoscopic Wilms nephroureterectomy
[65]. Despite International Society of Pediatric Oncology (SIOP)
and Children’s Oncology Group (COG) protocols requesting
more than six lymph nodes during Wilms nephroureterectomy,
the median number of nodes obtained during both open and minimally invasive resections is approximately four. In this case
report, 2mL of 2.5mg/mL ICG was injected into the normal renal
parenchyma near the tumor in 0.5mL aliquots. Seven hilar, suprahilar, pre-aortic, and para-aortic nodes subsequently demonstrated
uorescence, including several that would have gone undetected

12 Use ofFluorescence Guidance inPediatric Surgery
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without ICG.However, further investigation is warranted evaluating injection sites other than the renal parenchyma so as to prevent violation of COG guidelines and potential upstaging of the
tumor.
ICG lymphoscintigraphy can also be used for tumors of the
trunk and extremities. 4mL of ICG can be injected subcutaneously at a concentration of 1.25mg/mL in four quadrants around
the tumor intraoperatively (1mL per quadrant) [53]. In smaller
children, ICG is frequently visible through the skin when using a
near-infrared imaging device. Sentinel lymph nodes are best visualized using a contrast mode, whereas other modes, such as the
color-segmented uorescence mode, can be utilized for identication of regions with high uorescence intensity.
Further study is needed to evaluate the sensitivity and specicity of ICG lymphoscintigraphy for various cancer types in pediatric patients.
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Pediatric Plastic Surgery Applications
There has been increasing utilization of ICG in pediatric plastic
surgery for a variety of purposes, including assessment of ap
perfusion, evaluation of lymphedema, and management of lymphatic malformations. Reconstruction of congenital anomalies
has given way to the use of ICG for several operations unique to
pediatric patients. For instance, Hinchcliff etal. described the use
of intraoperative laser-assisted ICG angiography for a one-yearold with anterior plagiocephaly [66]. The patient underwent calvarial reconstruction for unilateral coronal synostosis, during
which tension during closure was encountered. ICG was safely
utilized to verify perfusion to the anterior and posterior aps prior
to closure. Tomioka etal. also utilized ICG to evaluate ap perfusion in a one-year-old who underwent web transplantation for
syndactyly [67].
In a case series of 433 pediatric free tissue transfers, Upton
etal. emphasized that technical considerations are more complex
in pediatric transfers given technical factors such as patients’
diminutive vessels, as well as challenges with postoperative

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immobilization [68]. Fried etal. described the use of ICG to verify perfusion of a free latissimus dorsi myocutaneous ap in a
six-month-old for reconstruction of a temporal fossa defect after
resection of a teratoma [69]. Intraoperative use of ICG in pediatric
patients may mitigate the morbidity of ap failures or vascular
complications requiring a return to the operating room for anastomotic revisions or ap repositioning [68]. Martins etal., in their
case series of pediatric patients undergoing rst-stage autologous
total ear reconstruction, found that patients in the intraoperative
laser-assisted ICG angiography treatment group were signicantly less likely to undergo surgical revision in comparison to the
non-ICG group [70].
ICG can also be used for real-time imaging of lymphatic anatomy and ow in the case of lymphedema or lymphatic malformations. ICG can detect lymphatic channels within one to two
centimeters of the skin surface in the absence of fascia, muscle, or
bone overlying the channels [33, 34]. Injection of ICG can aid in
the visualization of lymphatic channels, valves, and ow, which
can facilitate staging and management [71, 72]. Greives et al.
injected 12.5μg of ICG in 0.05mL of saline into the dorsum of
each hand and foot to evaluate lymphatic uptake in a 21-monthold with congenital lymphedema of the right hand and arm [73].
Imaging demonstrated normal lymphatic anatomy with decreased
lymphatic contractile function of the right upper extremity relative to the unaffected extremities, which aided in determining
appropriate management.
ICG can also facilitate identication, resection, and classication of lymphatic malformations. Shirota etal. used ICG to aid
complete resection of a lymphatic malformation in the abdominal
wall of a 15-year-old male [74]. The patient had failed management with sclerotherapy three times and MRI alone had failed to
adequately determine the extent of the tumor. Kato etal. similarly
used ICG lymphography to identify lymphatic malformations
originating throughout the body in 20 pediatric patients ages
11months to 10years [75]. They identied four classic ow patterns: (1) strong detectable inow, (2) multiple small observable
inows, (3) supercial lymph ow over a lesion, and (4) ow
around a lymphatic malformation without connection to the
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