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18 Radioguided Sentinel Lymph Node Mapping and Biopsy in Colorectal Cancer
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Additional H&E histopathologic analysis of
serial sections allows for the identifi cation of
micrometastatic disease in up to 20 % of lymph
nodes determined to be negative by standard
H&E methods [ 13 ]. However, performing H&E
histopathologic analysis of sections can be technically challenging and time consuming, as well
as entailing signifi cantly greater cost. Other histopathologic methods utilized for more accurate
assessment of the status of the regional lymph
nodes, such as immunohistochemistry using antibodies against human cytokeratins or RT-PCR,
require even more time and incur an even higher
cost. Therefore, what would be most useful and
relevant is a more careful evaluation of a selected
group of lymph nodes that have the highest probability of containing metastatic cells, i.e., the sentinel lymph nodes (SLNs) [ 4 , 6 – 10 , 14 – 16 ,
20 – 23 , 27 , 28 ].
The concept of SLN biopsy in colorectal cancer is currently not analogous to the similar procedure employed in cases of melanoma, breast
cancer, or Merkel cell carcinoma, where it has
direct implications for further therapy. En bloc
resection of the tumor with systematic lymph
node resection and central vessel ligation is the
gold standard in colorectal cancer. SLN biopsy
would allow a more comprehensive diagnosis of
the status of the lymphatic system, which, as
already stated, may be underestimated during
the normal staining. This benefi t is attributable
to the identifi cation of cancer cell foci that are
impossible to verify when using the H&E procedure [
4 – 6 , 8 , 9 , 17 , 22 ]. The identifi cation of
micrometastases in SLNs during the more thorough analysis may suggest the presence of
metastases in non-SLNs. This idea was originally put forward in single studies, but in a metaanalysis by Des Guetz et al. in 2007, it was
emphasized that standard histopathology of
lymph nodes in colorectal cancer delivers less
diagnostic and prognostic information than does
thorough examination of the lymph nodes identifi ed during lymphatic mapping [ 7 , 14 , 29 ].
Presently, SLN biopsy is recommended as an
examination that provides some additional,
prognostically relevant information, despite its
not entirely satisfying sensitivity. The results of
the procedure depend on a series of conditions
that infl uence the quality of the procedure [
19 , 30 ].
Performance of lymphatic mapping in the rectum is less reliable than in the colon owing to the
different anatomy. The principle of oncological
radicality associated with TME requires the
mesorectal fascia to remain intact during surgery.
This makes it impossible to apply the dye and to
search for lymph nodes intraoperatively. Another
issue is neoadjuvant radio- or radiochemotherapy, which affects the vessels and lymph nodes in
the vicinity of the tumor. In principle, patients
with rectal cancer should be excluded from the
analyzed material, or the procedural calculations
presented for them should be presented separately [ 10 , 11 , 20 ].
Table 18.1 provides a short overview of studies of the use of SLN biopsy in colorectal
cancer.
18 ,
18.1.2 Inclusion Criteria
In order to qualify for SLN biopsy, patients typically have to meet the following criteria: provision of patient consent, age over 18, satisfactory
general condition (ASA I–III), primary histopathologically confi rmed resectable colorectal
cancer, no previous surgical interventions in the
colon or its mesentery (including appendectomy
in the superior proximal right half of the colon),
and no allergies to contrast agents. Patients with
previous lymphadenectomy (regardless of the
reasons), pregnant women, patients who have
lymph nodes intraoperatively suspected of harboring metastases, tumors infi ltrating neighboring organs, remote metastases, or synchronous
cancer and patients undergoing emergency procedures (obstruction, massive bleeding, perforation) are excluded.
In some studies, several further factors have
been taken into consideration in assessing
whether patients qualify for SLN biopsy, i.e.,
anthropometric data, intraoperative appearance
of the tumor, and macroscopic and microscopic
characteristics at histopathology [
35 , 37 , 40 , 46 – 51 ].
5 , 7 , 17 – 20 , 29 ,
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IHC/
RT-PCR
Upstaging
(%)
NPV
(%)
FNR
(%)
Sensitivity
(%)
Accuracy
(%)
D. Murawa et al.
% of
patients
with CC DR (%)
70 70 99 96 91 9 – – Yes
Arch Pathol Lab Med
22 ] 2000
Wiese [
33 83 100 100 100 0 100 50 Yes
J Clin Oncol
32 ] 2001
Bilchik [
26 84 58 94 67 33 94 7 No
Dis Colon Rectum
27 ] 2001
Esser [
78 78 97 95 92 8 – 24 Yes
J Gastrointest Surg
8 ] 2002
Wood [
100 100 97 95 91 5 – 24 Yes
Eur J Cancer
33 ] 2002
Bilchik [
48 100 98 79 38 62 76 8 Yes
Am J Surg
34 ] 2001
Feig [
102 85 96 96 92 8 – 29 Yes
J Clin Oncol
14 ] 2003
Bilchik [
31 100 87 78 50 50 71 11 Yes
World J Surg
35 ] 2003
Viehl [
No. of
patients
with CC
74 86 99 96 91 9 – 18 No
Ann Surg Oncol
31 ] 2000
Saha [
Table 18.1 Parameters achieved in SLN biopsy in colon cancer, published by selected authors after the year 2000
Author Year Journal
336 83 99 – 88 12 – 13 Yes
Dis Colon Rectum
11 ] 2004
Saha [
106 88 99 96 86 16 – 5 Yes
Arch Surg
21 ] 2004
Dan [
72 100 92 80 46 54 75 0 no
Ann Surg
15 ] 2004
Bertagnolli [
209 80 100 96 92 8 – 13 Yes
Semin Oncol
36 ] 2004
Saha [
97 73 100 95 88 12 – 23 Yes
Arch Surg
4 ] 2006
Bilchik [
408 82 98 96 90 10 93 – Yes
Am J Surg
10 ] 2006
Saha [
69 100 93 20 46 54 73 5 Yes
Am Surg
37 ] 2006
Thomas [
69 100 97 96 89 11 93 – Yes
Int J Colorectal Dis
38 ] 2007
Kelder [
13 48 93 84 83 17 – 8 Yes
Acta Chir Belg
39 ] 2007
Murawa [
315 100 85 86 54 46 80 21 Yes
Ann Surg
40 ] 2007
Bembenek [
120 100 99 83 59 41 78 – Yes
Ann Surg Oncol
6 ] 2008
Lim [
22 42 91 80 67 33 67 25 Yes
J Surg Oncol
20 ] 2008
Quadros [
48 47 100 97 – – 95 19 Yes
Hepatogastroenterology
41 ] 2009
Ivanov [
31 100 90 71 33 67 46 5 Yes
Colorectal Dis
42 ] 2011
Retter [
38 100 95 100 100 0 100 – No
Turk J Gastroenterol
43 ] 2011
Albayrak [
100 100 99 94 83 17 91 10 Yes
Int J Colorectal Dis
44 ] 2011
Murawa [
43 51 74 84 62 38 – 10 No
74 100 89 84 55 45 80 15 Yes
Rom J Morphol Embryol
World J Surg
45 ] 2011
46 ] 2013
Vilcea [
Viehl [
CC colon cancer, DR detection rate, FNR false-negative results, NPV negative predictive value, IHC immunochemistry
18 Radioguided Sentinel Lymph Node Mapping and Biopsy in Colorectal Cancer
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18.1.3 Prognostic Signifi cance
of Micrometastases in SLNs
The prognostic signifi cance of micrometastases
has not yet been defi nitively established. What
has been proven is the lack of clinical relevance
of isolated cancer cells found in lymph nodes
[ 10 , 52 – 59 ]. Furthermore, few studies have ana-
lyzed the issue of prognosis in colon cancer
patients in whom micrometastases have been
detected in the SLN. In the Sirop et al. study in
2011, 109 patients with colorectal cancer were
investigated, with a follow-up of at least 5 years.
The SLN was analyzed through serial dissections
and immunohistochemistry. In 14 patients,
micrometastases were confi rmed in the SLNs.
All of these patients received adjuvant treatment.
5-year survival in the group with micrometastases after chemotherapy was 100 %, compared
with 96.2 % in the pN0 group and 75 % in the
pN+ group. Owing to the small group size, this
analysis did not achieve statistical signifi cance
( p = 0.07) [ 3 ].
In a study in 2014, 55 patients with colon cancer after SLN biopsy were compared with a control group of 110 patients adjusted for
tumor-related factors and operated on without
SLN biopsy. The average number of examined
lymph nodes in the clinical and control group differed signifi cantly, being nine and seven, respectively ( p = 0.03). Immunochemistry resulted in
upstaging owing to the detection of metastases in
3 of 38 SLNs initially considered true negative.
The 5-year survival rates differed signifi cantly in
the two groups: 83 % in the SLN biopsy group
vs. 69 % in the control group with no SLN biopsy
( p = 0.03). Furthermore, within the SLN group,
the 5-year survival rate was higher in SLNnegative patients (91 % vs. 76 %; p = 0.04). The
authors emphasized the excellent prognosis in
SLN-negative patients when using H&E stain
and immunochemistry together with automated
microscopy [
The studies utilizing molecular biology techniques (RT-PCR) have revealed that the frequency of discovery of small tumor deposits is
statistically higher in the SLN than in other analyzed lymph nodes [ 4 , 26 ].
60 ].
One of the largest studies analyzed 192
patients with colon cancer. In 42 (22 %) patients,
aberrant lymphatic drainage was observed which
changed the scope of the resection. In 19 patients
with extended scope of resection, metastases
were found in lymph nodes located beyond the
standard resection margin, and in two of these
patients, these lymph nodes were the only sites of
metastases. Furthermore, metastases to lymph
nodes were detected in 62 % of patients in whom
the scope of resection was extended after lymphatic mapping, compared with only 43 % of
those who underwent standard resection. In the
extended resection group, an average of 17.6
lymph nodes was examined, while in the standard resection group, the average was 15.8.
Analysis of the data indicates that aberrant lymphatic drainage infl uences disease management,
assessment of the disease stage, and, to a limited
extent, survival [ 66 ].
18.2 Lymphatic Drainage
of the Colon and Rectum
Lymphatic vessels in the colon run together
with blood vessels (Fig. 18.1 ), which is the rea-
son why colon resection should be accompanied by resection of the regional lymph nodes
from the vicinity of the superior and inferior
mesenteric vessels. The regional lymph nodes
associated with the colon are divided into four
groups:
1. Lymph nodes, located subserously in the
intestinal wall.
2. Paracolic lymph nodes, located along the mar-
ginal artery.
3. Mesocolic lymph nodes, located along arter-
ies. These include:
• Ileocolic lymph nodes, which are divided
into prececal, retrocecal, and appendicular
lymph nodes. Lymph fl ows along the ileocolic artery toward the superior mesenteric
lymph nodes.
• Left, middle, and right colic lymph nodes
transport lymph to the superior and inferior
mesenteric lymph nodes.
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Mesenteric root nodes
Lt. lumbar nodes
Intermediate
(mesocolic) nodes
Paracolic nodes
Epicolic nodes
Fig. 18.1 Lymphatic drainage and regional lymph nodes associated with the colon (Source: Skandalakis et al. [ 61 ] )
• Inferior mesenteric lymph nodes, which
are located in the sigmoid colon mesentery
and along the superior rectal artery. They
gather lymph from the sigmoid colon and
the superior part of the rectum.
4. Major lymph nodes located by the inferior and
superior mesenteric arteries bifurcation. These
include inferior mesenteric lymph nodes, periaortic lymph nodes, and left perilumbar lymph
nodes [
61 , 62 ].
lymph nodes located at a signifi cant distance
from the tumor.
The prevalence of aberrant lymphatic drain-
age has generally been reported to be up to 20 %
32 , 65 , 66 ]. Drainage of this nature infl uences
[
the scope of lymphadenectomy since “aberrant”
lymph nodes are potential locations for “skip
metastases” [
5 , 8 , 11 , 16 , 22 , 67 ]. In some cases,
the fi rst lymph nodes to become dyed are those
on the opposite side of the colon. Instances of
lymphatic drainage from the transverse colon
Several studies show that in more than 80 % of
cases, the fi rst metastatic lymph node in colorectal cancer is a paracolic lymph node located 5 cm
or less from the tumor (Fig. 18.2 ) [ 8 , 11 , 29 , 47 ,
63 , 64 ].
Beside this classic lymphatic drainage, aberrant drainage within the regional lymph nodes
can exist. Such drainage leads directly to main
lymph node stations near the superior and inferior mesenteric vessels or to colic and paracolic
through the greater omentum to the splenic hilar
lymph nodes have also been published [ 8 , 11 ].
Moreover, tumors located in the hepatic fl exure
can, in about 5 % of cases, metastasize to lymph
nodes located around the head of pancreas and in
about 4 % of cases to omental lymph nodes [ 68 ].
In some individual studies, a higher rate of
aberrant lymphatic drainage reaching up to 29 %
has been observed in patients undergoing
lymphatic mapping. Sometimes, however, the
18 Radioguided Sentinel Lymph Node Mapping and Biopsy in Colorectal Cancer
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Fig. 18.2 Distribution of the fi rst metastatic lymph node
in colorectal cancer (Source: Bembenek [
51 ] )
Inf. mesenteric
identifi cation of such drainage results from
methodological shortcomings, such as dye migration during the procedure or administration of the
tracer into the intestinal lumen (rather than intermurally), where it is absorbed by the mucous
membrane at a location remote from the primary
tumor [ 23 ].
The introduction of modern techniques, such
as lymphoscintigraphy, has allowed more precise
determination of the clinical anatomy of lymphatic drainage of the rectum, whose pattern does
not fully match the vascular pattern (Fig. 18.3 ).
Lymph from the superior third of the rectum is
drained from the pararectal lymph nodes into the
superior rectal lymph nodes and then into the
inferior mesenteric lymph nodes. These lymph
nodes are often the fi rst sites of metastases: in
artery nodes
Fig. 18.3 Lymphatic
drainage and regional
lymph nodes associated
with the rectum (Source:
Skandalakis et al. [
61 ] )
Sup. rectal nodes
Hypogastric (internal
iliac) nodes
Pectinate line
Inguinal nodes
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most cases, metastases are located 3 or fewer
centimeters from the primary tumor, but in 25 %
of patients, they are situated very close to the
superior rectal vessel bifurcation. Drainage from
the remaining part of the rectum, located below
the superior third but proximal to the mucocutaneous junction, takes place parallel to the middle
rectal artery and its branches on the lateral pelvic
wall or through the levator ani muscle along the
inferior rectal artery; both these routes end in the
internal iliac lymph nodes, common iliac lymph
nodes, and lumbar trunk. Metastases to these
lymph nodes are found in up to 12 % of patients.
Drainage from tissues located below the mucocutaneous junction (anal canal) is not typical and
does not take place in parallel to vessels. Lymph
ducts run anterior and posterior to the perineum,
together with ducts draining the nearby skin, and
terminate in the superfi cial inguinal lymph nodes.
Drainage via the external iliac lymph nodes takes
place toward the lumbar trunk [ 61 , 62 , 69 – 73 ];
this route of spread is signifi cant in tumors
located in the inferior part of the rectum (possible
metastases to inguinal lymph nodes) and above
all in squamous cell carcinoma of the anal canal
[ 74 – 77 ].
18.3 Colorimetric Markers: Mode
of Administration
and Limitations
The most commonly used tracers in lymphatic
mapping in colorectal cancer are colorimetric
markers. In Europe, Patent Blue V (sulfan blue,
E131) is used most frequently in SLN marking,
while in North America, the most frequently used
dye is isosulfan blue – Lymphazurin. Less frequently used tracers include Evans Blue (T-1824),
methylene blue, and indigo carmine. Soluble
blue dyes are lymphotropic; they bond with
endogenous protein through sulfonation and are
retained in lymph ducts [ 7 , 9 , 20 , 21 , 26 , 27 , 78 ,
79 ]. The use of colorimetric dyes does not require
any additional technology, nor does it prolong the
procedure signifi cantly (it does so by 5–10 min
on average) [ 22 , 26 , 27 ]. A potential complica-
tion in the case of blue dyes, such as isosulfan
blue and Patent Blue V, is allergic reactions,
which occur in 1–1.5 % of cases [
reactions include urticaria (hives), itching, nausea, hypotension, and, in very rare instances, lifeendangering anaphylaxis. An additional problem
is interference with pulse oximeter readings during the procedure [ 83 – 86 ].
As an alternative to blue dyes, fl uorescent
dyes such as indocyanine green can be used.
These dyes yield satisfactory results in terms of
detection and sensitivity in both open surgery and
laparoscopy. However, additional technological
assistance is required in the form of an infrared
light camera to allow observation and analysis of
the fl uorescence. The rare occurrence of severe
allergic reactions to indocyanine green needs to
be underlined [ 87 , 88 ].
Technical aspects of dye administration are
very important. In the vast majority of cases, dye is
administered intraoperatively via subserosal injection. No advantage of submucosal injection during
colonoscopy has been demonstrated [ 5 , 7 , 26 ]. It
needs to be underlined that unskilled administration of the dye – with injection into the intestinal
lumen – may result in its absorption at a remote
location (as described in Sect. 18.2). Spilling the
dye outside the tumor is also problematic, since it
makes it impossible to fi nd the right node after the
mesentery has been stained [ 7 , 10 , 16 , 21 , 26 ].
Dyes should be administered intraoperatively,
with in vivo lymphatic mapping. From a technical standpoint, the staining and mapping of the
lymph nodes ex vivo is simpler. Ex vivo mapping, however, may be considered reliable only
when the section and the mesentery have
remained intact during the resection (operating in
exact anatomic planes). Identifi cation ex vivo
alone, done after the administration of dye during
the operation, without marking the lymph node
with, for example, a suture or a clamp, has a satisfactory detection rate but entails a signifi cantly
higher rate of false-negative results. This is especially true when the duration of studies following
dye injection extends toward 100 min. The falsenegative rate may then even reach 45–60 %, rendering the SLN biopsy clinically useless [
In the prolonged interval between dye administration and lymph node identifi cation, the marker
80 – 82 ]. These
89 , 90 ].
18 Radioguided Sentinel Lymph Node Mapping and Biopsy in Colorectal Cancer
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relocates, sometimes resulting in loss of staining
of the primary nodal station or in the marking of
other nodal groups which are not composed of
SLNs [ 4 , 8 , 9 , 14 , 17 , 21 , 26 , 33 , 36 , 48 , 91 ].
18.4 Role of Radiocolloids
in Lymphatic System
Mapping
The use of radiocolloids is restricted by various
attendant problems and limitations, most of which
are due to the complexity of dealing with radioisotopes. Further problems are of a legal nature. In
many countries, formal authorization is required
from medical personnel, which limits the number
of people allowed to inject the isotope [ 26 , 47 , 94 ].
The advantage of radiocolloids is the absence of
allergic reactions and lack of interference with
equipment monitoring vital signs [ 78 ].
The radiotracers most often used are
(especially in Japan) and
99m
Tc-sulfur colloid
(especially in North America) [ 92 ], but
albumin may also be administered [ 93 ]. In some
cases, endoscopic examination with submucosal
injection can be performed a day before the operation [ 7 , 16 , 20 , 26 , 47 , 63 , 94 ]. Here it must be
emphasized that only about 10 % of the adminis-
99m
tered
Tc migrates from the site of injection to
lymph nodes. Taking into account the half-life of
99m
Tc, which is 6 h, the activity in the lymph
nodes at 12 h after administration during preoperative endoscopy (via submucosal injection)
may be too weak to enable SLN identifi cation
[
47 ]. From this perspective, intraoperative admin-
istration of the radiocolloid (at a suitably set
dose) seems advantageous; however, administration of the radiocolloid on the day of surgery
(preferably no more than 2 h before the operation) will also be adequate [ 47 , 95 ].
Owing to the size of the molecules, radiocolloids may be expected to travel more slowly in
lymph channels than do blue dyes, thereby permitting more precise identifi cation of SLNs.
Moreover, the larger size of radiocolloids, compared with blue dyes, causes them to remain longer within the fi rst draining lymph node [ 78 , 94 ,
96 ]. A real problem, however, is the fact that
99m
Tc-tin
99m
Tc-
radiocolloid migrates more rapidly in intestinal
lymphatic channels than in breast cancer or melanoma, thus increasing the probability of observing more “hot” lymph nodes [
63 ]. The use of
handheld gamma probes means that, to a certain
degree, radiocolloids allow for easier identifi cation of lymph nodes located deep within the intestinal mesentery, where blue dye may not be
readily visible. It should be emphasized, however,
that the SLN identifi cation process can be imprecise and is sometimes more indicative of the general pattern of lymphatic fl ow through the
lymphatic channels rather than any particular
lymph node. Another problem is the “shine
through” effect that results from the overlap of
radioactivity which can be encountered when the
tumor is in close proximity to the SLN candidates.
The minimum cutoff value for the identifi cation
of any given SLN candidate with the gamma
detection probe is generally defi ned as a count
rate greater than twice the background count rate.
This background radiation is described as radiation of tissues located remotely from the site of
injection and from the intestinal mesentery, measured in three independent places [ 14 , 78 , 93 , 96 ].
Therefore, when performing submucosal injections, it is necessary to repeat lymphoscintigraphy
2 or 3 times before the operation, to exclude spillage of the marker or contamination of the abdominal cavity [ 63 ]. It should be noted that when
performing intraoperative subserosal administration, all contaminated materials (needles, syringes,
gloves, swabs, setons) must be removed from the
operation site both to ensure adequate radiation
protection and to exclude the possibility of interference in the process of lymphatic mapping [
78 ].
Some studies have concluded that lymphatic
mapping using radiocolloids does not improve
SLN biopsy in colorectal cancer, whereas others [ 47 ] have indicated that the combined radio-
colloid/blue dye method is associated with
improvement of quality and results in this setting [ 7 , 14 , 16 , 20 , 21 , 23 , 26 , 29 , 94 , 97 ].
Importantly, in comparison with the use of dye
only, double mapping leads to a statistically
signifi cant increase in the probability of fi nding
an SLN and of identifying metastasis within
that SLN [ 78 ].
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18.5 Intraoperative Detection
and Harvesting the SLN
in Colorectal Cancer
18.5.1 Standard SLN Biopsy Method
in Colon Cancer with the Use
of Blue Dye
According to the most commonly accepted protocol, after the abdominal cavity has been opened,
the fragment of colon to be resected is delicately
mobilized to avoid potential extensive damage to
lymphatic and vascular structures. Next, blue dye
(e.g., 2 ml of Patent Blue V dye) is administered
subserosally around the tumor by means of four or
more injections (Fig. 18.4 ). After 5–10 min, the
lymph ducts become dyed and visible (Fig. 18.5 ),
as do the fi rst lymph nodes (most often 1–4)
(Fig. 18.6 ). Lymph nodes are marked with a suture
(Fig. 18.7 ). At the end of the operation, they are
harvested separately to be examined as SLNs
(Fig. 18.8 ). The whole procedure of lymphatic
mapping, from administration of the dye to marking the SLNs with a suture, takes place intraoperatively, in vivo. In the further operation, a standard
en bloc resection is performed with a margin of
healthy tissues and mesenteric lymphatic system.
The method of administration and mapping is
similar when using fl uorescent dye. To make the
lymph fl ow visible and detect the lymph node,
however, special equipment is required that permits in vivo analysis of intraoperative images in
infrared (Figs.
18.9 and 18.10 ).
Fig. 18.5 Identifi cation of a dyed lymphatic channel
(Source: author’s materials)
Fig. 18.6 SLN in the process of dyeing (Source: author’s
materials)
Fig. 18.4 Subserous injection of the dye in the area
around the tumor (Source: author’s materials)
Fig. 18.7 Dyed SLN and lymphatic channel marked with
a suture (Source: author’s materials)
The results of SLN biopsy in colorectal cancer
using mapping with colorimetric tracers are
described in Table 1.1 .
18 Radioguided Sentinel Lymph Node Mapping and Biopsy in Colorectal Cancer
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Fig. 18.8 Dyed SLN (Source: author’s materials)
Fig. 18.9 Lymphatic mapping procedure in colon cancer
using indocyanine green and a Pulsion camera (Source:
author’s materials)
Fig. 18.10 SLN harvested using the indocyanine green
method; image in infrared light (Source: author’s
materials)
18.5.2 Clinical Use of Radiocolloids
in SLN Biopsy in Colon Cancer
Most of the available literature on SLN biopsies
performed at major colon cancer centers relates
to the blue dye method alone, without the combined use of radiocolloid. Due to the already
mentioned problems and limitations, as well as
the fact that they often provide diverging results,
methods using
erative gamma probe detection have been
described relatively rarely [ 98 ]. During surgery,
0.5–2.0 ml (or, in some cases, 3–5 ml) of 1 % isosulfan blue and then 1 ml of
in saline solution with an activity of 0.5–1.0 μCi
[ 6 , 14 , 78 , 96 , 97 ] are administered subserously
via several injections around the tumor. The
doses are increased signifi cantly (three- to fourfold) if the injection is performed submucosally
during endoscopy on the day before surgery [ 47 ].
During combined radiocolloid/blue dye mapping, blue dye (1–2 ml) and
min are used [ 93 ]. In patients undergoing total
endoscopic polypectomy, the expected diffi culties in intraoperative localization of the site of
polypectomy usually lead to a decision to perform submucosal injection of radiocolloid during
endoscopy prior to surgery, in combination with
the preoperative lymphoscintigraphy. Endoscopic
administrations are also described as standard
procedures when combined with lymphoscintigraphy performed around 4-h post injection. The
injection is typically performed submucosally in
four rectangles around the tumor, but in the event
of technical diffi culties, it is limited to the tumor’s
posterior edge. It is worth noting that performance of endoscopy shortly before or during the
surgery will entail intestinal distension, complicating the whole surgical procedure [
potential benefi t of administering radiocolloids
before surgery is the possibility of performing
lymphoscintigraphy and visualizing potentially
aberrant lymph fl ow prior to surgery. Furthermore,
due to complementary planar mapping, it is also
possible to determine the depth of the lymph
nodes. Lymphoscintigraphy enables identifi cation of the nodes before surgery in more than
75 % of patients; however, in around 10 % of
99m
Tc-sulfur colloid and intraop-
99m
Tc-sulfur colloid
99m
Tc-labeled albu-
47 ]. The
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cases, the nodes are not found in vivo. In the
25 % of patients in whom the lymph nodes have
not been identifi ed before surgery, this is done
during intraoperative mapping while using the
gamma detection probe [ 47 , 78 ].
Intraoperatively, dyed lymph nodes are usually identifi ed approximately 1–10 min after the
administration of the dye, and they are then
marked with a suture. Next, the identifi cation is
performed using a handheld gamma detection
probe (usually within 30 min following intraoperative radiocolloid administration). As previously mentioned, the minimum cutoff value for
identifi cation of any given SLN candidate with
the gamma detection probe is generally defi ned
as twice the background count rate [ 6 , 14 , 78 ,
93 , 96 ]. In the majority of studies utilizing the
combined radiocolloid/blue dye method of
SLN biopsy, the SLN identifi cation rate
approaches 100 %, exceeding the rate achieved
by the blue dye approach alone by several percentage points [ 6 , 14 , 47 , 78 , 96 ]. Less optimal
results, approximately in the 90 % range, are
reported using the radiocolloid SLN biopsy
approach alone with the gamma detection probe
[ 47 , 78 ]. The accuracy of the combined radio-
colloid/blue dye method of SLB biopsy in predicting the status of the regional lymph nodes is
generally >90 %, barring some methodological
fl aws [ 14 , 78 , 96 ]. The relative numbers of
blue-dyed, radioactive, and blue/radioactive
SLNs identifi ed by the combined radiocolloid/
blue dye method vary: several studies have
indicated the detection of signifi cantly more
blue-dyed lymph nodes than radioactive or
radioactive/blue lymph nodes, while others
indicate a greater number of radioactive or
radioactive/blue lymph nodes than blue-dyed
lymph nodes [
been found that the combined radiocolloid/blue
dye method more accurately recognizes SLNs
with metastases [ 47 , 78 ].
Several recent studies have described the use
of radiocolloid alone for SLN mapping and
biopsy in patients with colon cancer [ 94 , 95 ]. The
fi rst study utilized the submucosal injection of
radiocolloid 2 h before surgery, with intraoperative identifi cation performed with a gamma
14 , 78 , 96 , 97 ]. In general, it has
detection probe. The authors demonstrated good
results, with a detection rate of 91 % and an accuracy of 97 % [
Taking into account the abovementioned data,
the various technical diffi culties, the need for
additional medical equipment, the required team
of medical specialists, the specifi city of lymph
fl ow in the intestinal mesentery, and, of course,
the added costs, it remains clear that at present
there is no consensus on the standard use of
radiocolloid in lymphatic mapping and SLN
biopsy for colon cancer [ 94 , 97 , 98 ].
95 ].
18.5.3 Clinical Use of Radiocolloids
in SLN Biopsy in Rectal Cancer
Because of the anatomic specifi city, the possibilities and technique of lymphatic mapping in
the rectum are different. In the case of rectal
cancer, intraoperative lymphatic mapping is
very diffi cult owing to the anatomic conditions
and the limited space within the lower pelvis
[ 93 ]. Additionally, the neoadjuvant radiochemo-
therapy for locally advanced rectal cancer
causes sclerosis and fi brosis of the lymphatic
system, changing and disturbing the patterns of
lymphatic fl ow [ 100 ]. Furthermore, lymphatic
mapping during the surgery results in damage to
the mesorectal fascia, which is at odds with the
purpose of total mesorectal excision, acknowledged to be the gold standard in rectal cancer.
Therefore, the blue dye methods are predominantly used ex vivo, most often by folding the
rectum and administering 1–2 ml of blue dye
submucosally around the tumor. The combined
radiocolloid/blue dye method is also used, especially for tumors located in the middle and lower
parts of the rectum. In these cases, administration of the blue dye and radiocolloid is done
submucosally prior to surgery with the use of a
rigid rectoscope [
applying the tracers seems acceptable [ 10 , 17 ,
69 , 99 , 100 – 104 ]. The ease of access to rectal
cancer via the rectoscope facilitates trials in
SLN biopsy with the use of radiocolloids. The
radiocolloid may be administered about 16–18 h
(or more) before surgery, during endoscopy
78 , 100 ]. This method of
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