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416
D. Yang and M. H. Whiteford
ab
Fig. 23.2 Lateral spreading tumor with granular surface (LST-G) (a). Lateral spreading tumor non-granular type (LST-NG) highlighted by
arrows (b)
scopic resection of sessile colon polyps ≥20mm, Moss etal.
identied lesions with depression (Paris 0-IIa+IIc) to be a
risk factor for submucosal invasion [26]. Depressed lesions,
particularly those with ulcerations or gross wall deformity
should raise the suspicion of a deeply invasive cancer that
may not be amenable for endoscopic resection.
Supercial nonpolypoid lesions measuring more than
10mm in diameter that extend laterally rather than vertically
are also referred as laterally spreading tumors (LSTs). The
incidence of LST on routine colonoscopy is approximately
9% [31]. LSTs are broadly subclassied into the granular
(LST-G) or non-granular type (LST-NG) (Fig. 23.2) [30].
LST-G is characterized by a nodular appearance that can be
homogenous or mixed.
Similar to Paris classication, LST morphology is also
prognostic for the risk of invasion. Homogenous LST-Gs
have a low risk of local invasion (<2%) as compared to
LST-Gs with mixed-size nodules (as high as 30% for those
measuring more than 30mm in size) [32]. Conversely, LSTNGs have a smooth surface and can be either at or pseudodepressed. The risk of submucosal invasion is even higher in
LST-NGs with pseudo-depression, increasing from 12.5%
for LST-NGs<20mm to 83% in those >30mm in size [33].
In addition to polyp morphology and size, location is another
important factor for risk of submucosal invasion. In a prospective study of 2277 LSTs in 2106 patients referred for
endoscopic resection, Burgess et al. identied LST-NG or
LST-G mixed-type lesions located in the rectosigmoid colon
as having the highest risk for malignancy [34].
Polyp Surface Pit andVascular Pattern
The shape of the opening of the crypts in the epithelium, or
commonly referred to as pit pattern, has been shown to be
associated with histologic prediction. Staining the surface of
conventional chromoendoscopy (CE) facilitates the evaluation of these pits. However, the main drawbacks include the
cumbersome preparation and instillation of dyes, additional
procedural time, and the lack of availability of some of these
agents in many centers. Many newer generation endoscopes
are equipped to enhance imaging by digitally manipulating
and ltering the light source, e.g., narrow band imaging. This
form of optical digital CE has the advantage of being more
readily accessible and convenient to use, as opposed to conventional dye-based CE.
Kudo and colleagues rst highlighted the feasibility of
examining and classifying pit patterns to distinguish nonneoplastic from neoplastic polyps via magnifying endoscopy [35]. This scheme classies pit patterns into seven
types based on the pit appearance and structure (Fig.23.3).
Type I pits appear as round pits and are characteristic of
normal colon mucosa. Type II includes stellate or papillary
pits, which often correspond to hyperplasia. Type III-s pits
appear as tubular or round pits smaller than in type I,
whereas type III-L includes tubular or round pits larger than
those in type I.Type IV pits have a dendritic or gyurs-like
pattern. Type III to type IV pit patterns are often characteristic of adenomatous polyps, which can be resected endoscopically. Lastly, type Vi includes irregularly sized and
arranged pit patterns, while type Vn describes lesions with
an amorphous, nonstructured pit pattern. Both type Vi and
Vn are indicative of either supercial or deep submucosal
invasion, respectively, with only a select number of these
cases amenable to endoscopic resection and the rest requiring surgery [36–38].
As noted previously, narrowband imaging (NBI) is a
form of digital CE that facilitates detailed inspection of the
capillary mucosal pattern by ltering white light into spe-
23 Management ofMalignant Polyps
Fig. 23.3 Kudo pit pattern
classication. (Reused with
permission Tanaka etal. [96].
Copyright © 2006 Elsevier)
417
I
Round pit (normal pit)
II
IIIs
IIIL
IV
VI
Asteroid pit
Tubular or round pit that is
smaller than the normal pit
(Type I)
Tubular or round pit that is
larger than the normal pit
(Type I)
Dendritic or gyrus-like pit
Irregular arrangement and
sizes of IIIL, IIIS, IV type pit
pattern
VN
cic wavelengths that enhance the supercial microvasculature structures [39]. The Sano classication was the rst
published NBI magnifying endoscopic classication in
2006 [40] with several validation studies subsequently corroborating its usefulness in both qualitative and quantitative diagnosis of colorectal lesions [41–43]. In addition to
Sano, there has been multiple other classication systems
introduced in Japan over the years [44]. In an effort to
develop a simpler classication system that could be
adopted worldwide, particularly in non-Asian countries,
the Colon Tumor NBI Interest Group (CTNIG) headed by
both Eastern and Western expert endoscopists introduced
the Narrow-Band Imaging International Colorectal
Endoscopic (NICE) classication system in 2009 [45]. The
NICE classication categorizes lesions into three types
(1–3, and) based on color, vessels, and surface pattern
Loss or decrease of pits with
an amorphous structure
(Fig. 23.4). Type I lesions, typically hyperplastic or serrated lesions, are characterized by having same or lighter
color than the background, none or isolated lacy vessels,
and dark or white spots of uniform size. Adenomatous polyps are classied as type II and feature browner color when
compared to the background with brown vessels surrounding oval, tubular branched white structures. Lastly, type III
lesions show a dark brown background, disrupted or missing vessel pattern, and amorphous or absent surface pattern, which most often corresponds to lesions with deep
submucosal invasion [45]. The NICE classication system
has been validated as an important tool for neoplasia classication and depth assessment [45, 46]. In a multicenter
prospective study of 1634 consecutive patients with 2123
lesions >10mm in size, the NICE classication identied
those with deep invasion with 96.4% specicity [46].
418
NBI International colorectal endoscopic (NICE) Classification*
be suggested by an irregular vessel or surface pattern, and is often associated with atypical morphology (e.g., depressed area).
Color
Type 1 Type 2 Type 3
Same or lighter than background
Browner relative to background
(verify color arises from vessels)
D. Yang and M. H. Whiteford
Brown to dark brown relative to
background; sometimes patchy
whiter areas
Vessels
Surface
Pattern
Most likely
pathology
Examples
None, or isolated lcy vessels
coursing across the lesion
Dark or white spots of uniform
size, or homogeneous absence
of pattern
Hyperplastic
Brown vessels surrounding
white structures**
Oval, tubular or branched
white structure
surrounded by brown vessels**
Adenoma***
Has area(s) of disrupted or
missing vessels
Amorphous or absent surface
pattern
Deep submucosal
invasive cancer
* Can be applied using colonscopes with or without optical (zoom) magnification
** These structures (regular or irregular) may represent the pits and the epithelium of the crypt opening.
*** Type 2 consists of vienna classification type 3, 4 and superficial 5 (all adenomas with either low or high grade
dysplasia, or with superficial submucosal carcinoma). The presence of high grade dysplasia or superficia submucosal carcinoma may
Fig. 23.4 NBI International Colorectal Endoscopic (NICE) classication. (Reused with permission Hayashi etal. Copyright © 2013 Elsevier)
Depth ofInvasion
sion and other histological features often determine the risk
of lymph node metastasis and thereby the optimal treatment
The depth of invasion is the most important feature when
strategy.
evaluating resectability and risk for lymph node metastasis.
As previously alluded, polyps with dysplastic cells conned
to the muscularis mucosa are benign lesions that can be
Haggitt Classication ofPedunculated Polyps
cured endoscopically. Conversely, CRC is dened clinically
by the invasion of neoplastic cells through the muscularis
mucosa into the submucosa. The depth of submucosal inva-
In 1985, Haggitt and colleagues introduced a classication
system for protruded polyps based on the depth of invasion
Le
Le
Le
Le
Le
Pedunculated adenoma
1
2
3
23 Management ofMalignant Polyps
419
[47]. According to this system, lesions are classied as levels
0–4 (Fig.23.5). Level 0 corresponds to neoplastic cells limited to the mucosa without breaching the muscularis mucosa.
It should be noted that the terms “carcinoma in situ” or
“intramucosal carcinoma,” which were used for level 0
lesions, should no longer be used as these lesions are by denition benign given the negligible risk for metastasis due to
the absence of lymphatics in the mucosa layer. Levels 1–3
pertain specically to pedunculated polyps. Level 1 corresponds to a pedunculated polyp in which cancer cells invade
into the submucosa, but these changes are restricted to the
head of the pedunculated polyp. Levels 2 and 3 indicate cancer cells invading into neck of the polyp (junction between
the head and the stalk) and any region of the stalk, respectively. Lastly, level 4 indicates when cancer cells have
invaded into the submucosa of the bowel wall below the stalk
of the polyp.
Fig. 23.5 Haggitt
classication of pedunculated
and sessile polyps. (Reused
with permission Nivatvongs
[97]. Copyright © 2002
Elsevier)
vel 0
Kudo andKikuchi Classication ofSessile
Polyps
Both Kudo etal. and Kikuchi etal. introduced the concept
of classifying sessile polyps into three levels based on their
degree of malignant submucosal invasion (SMI): Sm1, invasion into the upper third of the submucosa; Sm2, invasion
into the middle third; and Sm3, invasion into the lower third
(Fig. 23.6) [48, 49]. This classication system has direct
clinical implications, as the risk of lymphatic spread is
directly proportional with the depth of submucosal invasion,
with the highest risk being in those lesions extending into
the deepest third of the submucosa (Sm3) [50]. The main
drawback of this system for routine clinical practice is the
need of a signicant portion of the submucosa within the
resected specimen in order to dene the deepest border of
the submucosa. Most polypectomy specimens are limited to
Adenocarcinoma
vel 1
Adenocarcinoma
vel 2
vel 3
vel 4
Fig. 23.6 Classication of
submucosal invasion (SM) of
malignant polyps. (Reused
with permission Mohamed
and Schoeld [98]. Copyright
© 2014 Elsevier)
Submucosa
Sm
Submucosa
Muscularis
propria
Subserosal connective tissue
Adenomatous
epithelium
Normal colonic
mucosa
Muscularis
mucosae
Sm
Submucosa
Muscularis
propria
Subserosal connective tissue
sessile adenoma
Sm
420
D. Yang and M. H. Whiteford
the middle or deep submucosal layer and do not extend
down to the muscularis propria, a landmark required to
determine SM1, SM2, and SM3 invasion. As such, this classication system has been further modied as to assess risk
of metastasis simply based on the depth of SMI from the
muscularis mucosa [51].
Depth ofInvasion andRisk ofLymph Node
Metastases
Kitajima etal. standardized histopathological evaluation of
SMI in CRC and determined that in pedunculated lesions,
the rate of lymph node metastasis was 0% for Haggitt level 1
and in level 2 or 3 when SM depth was <3000μm. For all
non-pedunculated lesions, the risk of lymph node spread was
0% if SMI was <1000μM, 3.9% if SMI was <2000μM, and
17.1% if SMI was ≥2000μM [52].
Histopathological Factors Inuence theRisk
ofLymph Node Metastasis inEarly Colorectal
Cancer
In addition to depth of invasion, several histopathological
features have been associated with an increased risk of lymph
node metastasis. In a study of 292 early invasive CRCs with
surgical resection, Ueno etal. identied potential parameters
associated with nodal involvement [52]. Unfavorable tumor
grade (poorly differentiated adenocarcinoma and mucinous
adenocarcinoma vs well- and moderately differentiated adenocarcinoma), lymphovascular invasion (evidence of cancer
involvement of lymphatic and/or venous vessels), and tumor
budding (single or cluster cancer cells) were all qualitative
parameters associated with lymph node metastasis and unfavorable prognosis with endoscopic resection [52]. Indeed, in
a subsequent systematic review and meta-analysis including
23 studies and 4510 patients, the main factors associated
with lymph node spread included depth of SMI>1000μm
(OR 3.87; 95% CI: 1.50–10.00, P = 0.005), unfavorable
tumor grade (OR 5.60; 95% CI: 2.90–10.82, P < 0.0001),
lymphovascular invasion (OR 4.81; 95% CI: 3.14–7.37,
P<0.0001), and tumor budding (OR 7.74; 95% CI: 4.47–
13.39, P<0.001) [53].
Endoscopic Resection ofMalignant Polyps
The adequacy of endoscopic resection is dictated by the
lesion’s risk for lymph node metastasis, given that endoscopic resection does not remove or sample the lymph node
drainage basin. Overall, endoscopic resection is the preferred
treatment for benign precursor lesions (those without malig-
nant invasion into the submucosa) given the negligible risk
for lymph node metastasis and sparing the patient the signicant cost, morbidity, and mortality associated with surgery
[54, 55]. With advances in endoscopic resection techniques,
select malignant polyps can also be adequately removed
endoscopically, provided that SMI is <1000μm and there are
no unfavorable histopathological factors [53].
Endoscopic Mucosal Resection (EMR) Technique
In conventional terms, EMR in the GI tract refers to the technique of submucosal injection underneath the target lesion
(lift) followed by snare resection. The purpose of the submucosal lift is to separate the target lesion from the underlying
muscularis propria as to facilitate endoscopic resection.
Submucosal injection also enhances polypectomy by making
the tissue easier to resect with a snare; decreases bleeding
and perforation risk by increasing the distance between
mucosa and muscularis propria layers; and improves the
chances of complete resection. Normal saline has been commonly used as the submucosal injection uid given its safety
and low cost. However, more recently, the use of viscous
solutions in randomized trials has demonstrated a longerlasting lift when compared to normal saline [56]. A contrast
agent (indigo carmine or methylene blue) is usually added to
the injection uid. This blue-dyed injection uid allows
staining of the submucosa which permits differentiation of
the layers of the colonic wall during endoscopic resection
and early recognition of any deep injury to the nonstaining
muscle wall layer. As liquid is injected into the bowel wall,
the loose connective tissue of the submucosa can be separated, and the thin mucosal layer lifted up off of the muscularis propria. The “non-lifting sign,” rst described by Uno
in 1994, refers to the phenomenon whereby a mucosal cancer has invaded into the submucosa and prevents the mucosal
layer from being detached and elevated [56]. Non-lifting
sign can also be observed when the submucosal layer has
been scarred by previous submucosal tattoos, biopsy, or
resection attempts.
It is critical to remember that the rst endoscopic resection has the highest likelihood for successful complete polyp
removal. The location of the injections for submucosal lift is
performed strategically as to direct the target lesion toward
the lumen and away from any folds. Deection of the endoscope tip is performed during submucosal injection (known
as dynamic injection) in order to help shape the submucosal
mound favorably for EMR.Lesions should be removed in as
few pieces as safely possible.
Following submucosal lifting, resection during EMR is
performed with a snare. There are many sizes and shapes of
snares, which usually range between 15mm and 20 mm in
23 Management ofMalignant Polyps
Fig. 23.7 Endoscopic mucosal resection (EMR) of a semicircumferential lateral spreading tumor granular mixed-type (LST-G
mixed) in the ascending colon. https://doi.org/10.1007/000-33d
421
piecemeal EMR have not been completely elucidated, but
incomplete resection at the lateral margins appears to be at
the heart of the problem. While recurrence of benign polyps
after piecemeal EMR can often be adequately treated endoscopically and new strategies have been introduced to reduce
the risk of residual tissue [57, 58, 61], piecemeal EMR of a
malignant polyp is considered non-curative. Piecemeal EMR
signicantly hinders histopathological evaluation, as the
fragmented tissue specimens compromise specimen orientation and interpretability of the resection margins. Hence, as
per the National Comprehensive Cancer Network practice
guidelines, patients with endoscopically curable malignant
polyps (limited SMI and favorable histopathological factors)
who undergo piecemeal EMR inevitably still require surgery
due to the high risk of understaging the lesion owing to the
compromised pathological interpretation [62].
Endoscopic Submucosal Dissection Technique
diameter. Larger and stiffer snares are generally used to
remove larger at lesions. Given the size of the snares, enbloc resection (one piece) can often be achieved for lesions
measuring ≤20mm, whereas piecemeal resection is required
for larger lesions. Accurate snare placement should involve
ensuring at least a 1 mm margin of healthy tissue at the
perimeter of the polyp. During piecemeal EMR, successive
pieces are removed in an orderly fashion, avoiding leaving
“islands” of neoplastic tissue within the resection plane. As
each section of the lesion is resected, the submucosal resection site should be washed and inspected for bleeding or
muscle injury. Finally, prophylactic hemostasis and completeness of polyp removal can be achieved by ablating any
visible submucosal vessels or islands of residual polyp with
a coagulation forceps (Fig.23.7).
Outcomes ofEMR ofColorectal Polyps
EMR has been shown to be both effective and safe for the
management of benign precursor colorectal polyps. In a prospective study of 1134 consecutive patients with mean lesion
size of 36.4mm, EMR was associated with complete resection in >90% of the cases [58]. Delayed bleeding is the most
common adverse event, which has been historically reported
in up to 7% of patients; albeit recent data suggest that prophylactic clip closure of the EMR resection site may reduce
the risk in selected cases [59].
The main limitation of EMR in the management of
colorectal polyps is the inability to resect lesions larger than
20mm in en-bloc fashion. Piecemeal EMR increases the risk
of recurrence, with varying rates ranging from 7% to 25%
[58, 60]. The factors responsible for polyp recurrence after
Endoscopic submucosal dissection (ESD) was initially
developed in Japan for the treatment of early gastric cancer
[63]. The main advantage of ESD over conventional EMR is
that it theoretically permits the en-bloc resection of any
lesion, irrespective of size. Given its efcacy and safety
among expert endoscopists in Japan, ESD has been expanded
to include lesions in other parts of the GI tract, including the
colon.
Delineation of the target lesion borders is often performed
by placing cautery marks lateral to the margins of the polyp.
Markings serve as a visual guide during dissection to ensure
a negative pathological margin. Following this step, similar
to EMR, submucosal injection is performed as to lift the
polyp and to create a cushion between the lesion and the
underlying muscularis propria. A viscous lifting solution is
routinely used during ESD as the longer-lasting mucosal lift
has been associated with increased procedural efciency and
safety [64, 65]. Upon completion of an adequate submucosal
lift, a circumferential mucosal incision is traditionally performed to penetrate the muscularis mucosa and allow visual
identication of the dye-stained submucosal space. After this
initial incision, the exposed submucosal tissue is further dissected by repetitive injections and cutting with the ESD knife
along the incision margins.
From a technical standpoint, ESD is a complex exible
endoscopic surgical procedure performed through an endoscope, hence, often described as “single-hand surgery with
no help from assistants to provide traction.” Maintaining
adequate visualization of the dissection plane during ESD is
often regarded the rate-limiting and most challenging aspect
of the procedure. Providing adequate countertraction to
expose the dissection eld is key, and multiple techniques
and novel platforms have been introduced, with promising
422
Fig. 23.8 Endoscopic submucosal dissection (ESD) of a large lateral
spreading tumor granular type (LST-G) in the rectum using the “pocketcreation” technique. https://doi.org/10.1007/000-33c
results [67, 68]. In addition, one of the challenges during
colorectal ESD is the rapid dissipation of the injected uid
from the mucosal incision line. As such, in 2016, the concept of the “pocket-creation” method was introduced
(Fig.23.8) [66]. Unlike conventional ESD in which a circumferential mucosal incision is performed around the
polyp initially, with the pocket-creation technique only a
small mucosal incision is initially performed. The endoscope is then inserted into this small opening and submucosal dissection/tunneling performed deep to the lesion, which
results in less dissipation of the injectate. Following completion of the submucosal dissection, the initial mucosal
incision is subsequently extended along the remaining margins of the lesion. In a retrospective study of 887 colorectal
lesions treated with ESD, when compared to conventional
ESD, the pocket-creation method was associated with
higher en-bloc resection rate (100% vs 96%; P < 0.001),
complete resection rate (91% vs 85%; P=0.03), and shorter
procedural time [69].
Outcomes ofESD forColorectal Polyps
Early case series on colorectal ESD from Asia reported reasonable en-bloc resection rates of approximately 80% but
were plagued by the frequency of serious adverse events,
including perforation occurring in up to 10% in some studies
[70]. However, with the development of dedicated ESD
devices as well as improved prociency in the technique,
subsequent large studies from Asia have reported en-bloc
and curative resection rates over 90–98%, with perforations
occurring between 2.5% and 5% of the cases and <1%
requiring surgical intervention [71, 72].
D. Yang and M. H. Whiteford
Although ESD has been rapidly embraced in Asia, the
transition of ESD to the Western Hemisphere has been
slower, particularly due to the technical complexity of the
procedure, its steep learning curve, and the relative limited
training opportunities in the West [73]. As such, initial studies have demonstrated lower complete resection and higher
complication rates when compared to studies originating
from Asia. In a systematic review and meta-analysis on clinical outcomes of ESD in 18,764 colorectal lesions, Fuccio
and colleagues demonstrated that complete (R0) resection
rate was signicantly lower in Western vs Asian countries
(71.3% vs 85.6%; P < 0.001) with a higher rate of both
delayed bleeding (4.2% vs 2.4%; P<0.001) and perforation
(8.6% vs 4.5%; P<0.001) [73, 74]. In a recent multicenter
study from North America, rectal ESD (n=171) was associated with an en-bloc and R0 resection rate of 82.5% and
74.9%, respectively and was curative in 81.8% of malignant
polyps with favorable histologic features [75].
For benign and malignant polyps located within the rectum, transanal endoscopic surgery (TES) is a desirable
option over exible EMR and ESD.While ESD of large polyps is largely performed piecemeal and limited to the submucosal plane, TES can be performed in either the
submucosal or full-thickness plane and is usually performed
en-bloc with low rates of specimen fragmentation (<10%),
positive margins (66–93%), and polyp recurrence (5–11%)
[76–80]. TES is also feasible for endoscopically challenging
polyps such as circumferential lesions and lesions which
extend down into the anal canal. The limiting factor for TES
is that the instruments are typically not exible and it may be
difcult to reach the proximal rectum [77].
Endoscopic Approach toMalignant Polyps
The rst critical step in the management of malignant polyps
is detailed lesion assessment as to potentially differentiate
those amenable for endoscopic resection and those with features suggestive of advanced disease that will require surgery. As previously described, endoscopic features suggestive
of deep SMI may include depressed lesions (Paris 0-IIc),
those with surface ulceration/excavation (Paris 0-III) with
abnormal/disrupted surface pit/vascular pattern (Kudo classication Type V/Vn and NICE type III). When a lesion with
suspected deep SMI is identied, biopsies should be obtained
from the portion of the lesion with such features and the
patient referred for surgical resection. The site of the lesion
should be inked with a tattoo for reference identication during surgery [81]. To improve polyp location at time of surgery, tattoo should be placed in multiple quadrants just distal
to the polyp, photographed, and clearly documented in the
colonoscopy report. The exception to the previous statement
includes pedunculated polyps (Paris Ip) that may have endo-
23 Management ofMalignant Polyps
423
scopic features of deep SMI limited to the head (Haggitt
level 0–2). In these cases, en-bloc resection at the level of the
stalk is associated with favorable prognosis [82].
All colorectal polyps without features of deep SMI,
including malignant polyps with supercial SMI and favorable histological characteristics, are potential candidates for
endoscopic resection. As mentioned previously, en-bloc
endoscopic resection is mandatory for the removal of malignant polyps, as assessment of depth of SMI and resection
margin status cannot be reliable obtained with a fragmented
specimen. Malignant polyps that are 2 cm or smaller can
often be removed en-bloc with EMR.For lesions >2cm in
size, ESD is usually required. Following endoscopic resection, the resected specimen should be pinned on a cork board
or similar material as to maintain its in situ architecture.
Placing the resected specimen in formalin without pinning
can result in curling of the edges, which can make differentiation between the lateral and deep resection margins challenging and render the measurement of depth of SMI
inaccurate [24, 83]. Endoscopic resection of a malignant
polyp is considered curative if the following criteria are met
on histopathological assessment: (1) all resection margins
are negative, (2) SMI<1000μm, (3) well to moderately differentiated tumor grade, and (4) absence of lymphovascular
invasion and/or tumor budding [84]. If endoscopic tattoo was
not performed at the index colonoscopy, a repeat colonoscopy is necessary within 1–2weeks and placement of a tattoo to facilitate endoscopic surveillance or intraoperative
localization at the time of surgical resection.
Malignant polyps and early cancers located in the rectum
are well suited for transanal endoscopic surgery (TES). As
with benign polyps, TES can remove the lesion en-bloc. It is
also possible to remove rectal lesions in full-thickness fashion where appropriate. This provides a “total biopsy” which
permits optimal pathologic evaluation for SM level of invasion, tumor budding, and other high-risk features. Patients
then can be better risk stratied and counseled regarding
need for repeat endoscopic procedure, surveillance, or radical surgery [85, 86]. The downside of full-thickness resection is the additional morbidity, long-term functional
derangements (especially for distal lesions), and the scarring
that occurs outside of the rectal wall, which can make subsequent proctectomy more challenging.
Prior to attempting endoscopic resection of a potentially
malignant polyp, it is advisable to obtain a carcinoembryonic
antigen (CEA) level for surveillance if the lesion is proven to
be malignant. Following the endoscopic resection of a malignant polyp, it is often advisable to obtain a baseline crosssectional imaging (chest and abdominopelvic computed
tomography) to exclude the possibility of metastatic disease.
While there is no consensus on the timing, experts advise
delaying endoscopic ultrasound or cross-sectional imaging
at least 3–4weeks after the endoscopic procedure as to allow
the bowel wall to heal and any reactive inammatory lymphadenopathy to subside [24]. This will avoid the problem of
reactive lymphadenopathy being classied radiographically
as metastatic spread, which could lead to overtreatment of
the patient.
Predicting theRisk ofResidual Mural Cancer or
Lymph Node Metastasis Following Endoscopic
Resection ofMalignant Polyp
Assessing the risk of occult lymph node metastasis in T1
colorectal cancers is an imperfect science. There is no single
histologic feature that can accurately predict this risk, yet
clinicians need some estimate of risk to counsel patients
regarding the decision to elect repeat endoscopic intervention, surveillance with watchful waiting, or radical surgical
resection. In order to have an informed discussion, it is necessary to estimate both the risk of occult residual cancer and
the risk of perioperative surgical morbidity and functional
outcomes following surgery. As mentioned previously, prognostic indicators for increased risk of residual cancer include
positive resection margin (less than 1mm, or indeterminant),
submucosal invasion less than 1mm, lymphovascular invasion, tumor budding, and poorly differentiated histology.
Multiple unfavorable features are also known to have an
additive risk [85, 87].
It is not uncommon for pathology reports to omit many of
these features as they have not been routinely included in
guidelines for synoptic reports [88]. Ideally, the pathology
slides should be reviewed at a multidisciplinary tumor board
by dedicated gastrointestinal pathologists to identify and
tally the number of high-risk features to better stratify the
risk of recurrence. This can then be used to counsel the
patient and guide management decisions.
The ACPGBI position statement for management of the
malignant polyp provides a useful risk stratication tool
(Table23.1). High-risk histologic features are weighted and
then added together to calculate a risk score and estimated
risk of residual disease [4]. Over a 3-year period, the tool
was utilized to guide the MDTs of a regional cancer network
in the UK in the management of 173 patients after endoscopic resection of malignant colorectal polyps. Thirty-seven
patients (21.4%) underwent primary surgical resection with
a residual disease rate of 43%, while 136 patients managed
with surveillance had a 4.4% recurrence [89].
Recurrence Following Endoscopic Resection
Given its higher en-bloc and curative resection rate when
compared to EMR, ESD is often advocated as the preferred
endoscopic approach for malignant polyps with supercial
424
D. Yang and M. H. Whiteford
Table 23.1 Criteria are based on histological description of endoscopically resected malignant polyp weighted for prognostic signicance of
each risk factor. Where more than one risk factor is present, the degree
of risk is added together to give a total risk score
Histologic criteria Degree of risk
Resection margin
<1mm
Resection margin
1–2mm
Pedunculated:
Haggitt level 4
Sessile: Kikuchi 2 2
Sessile: Kikuchi 3 4
Poor differentiation 3
Mucinous tumor 1
Tumor budding 1
Lymphovascular
invasion
Total
score
0 Very low <3% Routine follow-up
1 Low <5% Assess other factors,
2 Medium 5–10% Discuss risk/benet of
3 High 8–15% Discuss risks, err
≥4
Reused with permission [4] Copyright © 2013 John Wiley and Sons
Grade of
risk
Very high > 20% Recommend surgery
4
1
4
2
Estimated risk of
residual cancer
Recommended course
of action
close follow-up
surgery vs follow-up
toward surgery
unless patient unt
SMI (T1 CRC), particularly when larger than 2cm in size
[90]. Several studies have reported on the local recurrence
and prognosis following ESD of malignant polyps. In a retrospective study evaluating clinical outcomes of ESD in 310
consecutive colorectal neoplasms, of which 53 were T1
CRCs, disease-free survival was 100%, and no distant metastasis was observed, whereas all local recurrences (2%)
occurred in patients with piecemeal resection at a median
follow-up of 3 years [91]. Similarly, Yoda and colleagues
demonstrated that endoscopic resection of malignant polyps
with favorable histological features is associated with excellent oncological outcomes, with 5-year disease-free survival
and recurrence of 98% and 0.8%, respectively [92]. Based on
these data, patients who undergo endoscopic resection of
malignant polyps with favorable histologic criteria should be
informed that the risk of residual or recurrent disease, particularly after en-bloc resection, is minimal, but not zero.
Surveillance After Endoscopic Resection
The post-polypectomy surveillance guidelines published in
the USA and Europe have been mainly based on the aggregate data on the rate of metachronous advanced neoplasms
and CRC death [93, 94]. In the case of endoscopic resection
of malignant polyps, the risk of recurrence and/or metastatic
disease has been mainly reported to occur within 3–5years
[91–93]. The European Society of Gastrointestinal
Endoscopy (ESGE) recommends surveillance colonoscopy
at 6months following piecemeal endoscopic resection of all
colorectal polyps larger than 10mm; however, no denitive
recommendation is given specically for timing of surveillance post-resection of malignant polyps. Since local recurrence is rare following en-bloc resection, the Japan
Gastroenterological Endoscopy Society (JGES) suggest that
follow-up colonoscopy should be performed within 3years
after resection [84]. While experts suggest that tumor markers, such as carcinoembryonic antigen (CEA) and chest/
abdominopelvic computed tomography, should be periodically done for surveillance, there is no consensus on the
actual method or the timing of surveillance.
Conclusion
Endoscopic resection of low-risk T1 colorectal cancer is an
effective treatment in select patients. Detailed lesion assessment is crucial in determining the best therapeutic strategy.
Selected lesions with supercial SMI can be adequately
managed with en-bloc endoscopic curative resection with
either EMR or ESD.For malignant polyps or early cancers in
the rectum, TES is another alternative, which can also provide full-thickness en-bloc resection where appropriate. All
lesions with predictors of deep SMI should be referred to
surgery given the high risk for lymph node metastasis.
References
1. International Agency for Research on Cancer. Globocan 2018:
cancer fact sheets – colorectal cancer. IARC. http://gco.iarc.fr/
today/data.factsheets/cancers/10_8_9- Colorectum- fact- sheet.pdf.
2. Fleming M, Ravula S, Tatischchev SF, Wang HL, et al.
Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol.
2013;3:153–73.
3. Conteduca V, Sansonno D, Russi S, etal. Precancerous colorectal
lesions. Int J Oncol. 2013;43:973–84.
4. Williams JG, Pullan RD, Hill J, etal. Management of the malig-
nant colorectal polyp: ACPGBI position statement. Colorectal
Dis. 2013;15(Suppl 2):1–38.
5. National Comprehensive Cancer Network. Clinical practice
guidelines in oncology; colon cancer (v3.2018). Available at
https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.
6. Rex DK, Hassan C, Bourke MJ.The colonoscopist’s guide to the
vocabulary of colorectal neoplasia: histology, morphology, and
management. Gastrointest Endosc. 2017;86:253–63.
7. Winawer SJ, Zauber AG, Ho MN, etal. Prevention of colorectal
cancer by colonoscopic polypectomy. The National Polyp Study
Workgroup. N Engl J Med. 1993;329:1977–81.
8. Atkin W, Morson B, Cuzick J.Long-term risk of colorectal can-
cer after excision of rectosigmoid adenomas. N Engl J Med.
1992;326:658–62.
23 Management ofMalignant Polyps
425
9. Zauber AG, Winawer SJ, O’Brien MJ, etal. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N
Engl J Med. 2012;366:687–96.
10. Keum N, Giovannucci E. Global burden of colorectal cancer:
emerging trends, risk factors and prevention strategies. Nat Rev
Gastroenterol Hepatol. 2019;16:713–32.
11. World Health Organization. Classication of tumours of the
digestive tract. Lyon: IARC Press; 2019.
12. Dixon MF.Gastrointestinal epithelial neoplasia: Vienna revisited.
Gut. 2002;51:130–1.
13. Salmo E, Haboubi N.Adenoma and malignant colorectal polyp:
pathological considerations and clinical applications. EMJ
Gastroenterol. 2018;7:92–102.
14. Fleming M, Ravula S, Tatishchev SF, etal. Colorectal carcinoma:
pathologic aspects. J Gastrointest Oncol. 2012;3:153–73.
15. Heitman SJ, Ronskley PE, Hilsden RJ, etal. Prevalence of adenomas and colorectal cancer in average risk individuals: a systematic review and meta-analysis. Clin Gastroenterol Hepatol.
2009;7:1272–8.
16. Crockett SD, Nagtegaal ID. Terminology, molecular features,
epidemiology, and management of serrated colorectal neoplasia.
Gastroenterology. 2019;157:949–66.
17. Saito S, Tajiri H, Ikegami M.Serrated polyps of the colon and rectum: endoscopic features including image enhanced endoscopy.
World J Gastrointest Endosc. 2015;7:860–71.
18. Fearon ER, Vogelstein B.A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67.
19. Dow LE, O’Rourke KP, Simon J, etal. Apc restoration promotes
cellular differentiation and reestablishes crypt homeostasis in
colorectal cancer. Cell. 2015;161:1539–52.
20. Nakayama M, Oshima M.Mutant p53in colon cancer. J Mol Cell
Biol. 2019;11:267–76.
21. O’Brien MJ, Yang S, Clebanoff JL, etal. Hyperplastic (serrated)
polyps of the colorectum: relationship of CpG island methylator
phenotype and K-ras mutation to location and histologic subtype.
Am J Surg Pathol. 2004;28:423–34.
22. Bond CE, Liu C, Kawamata F, etal. Oncogenic BRAF mutation
induces DNA methylation changes in a murine model for human
serrated colorectal neoplasia. Epigenetics. 2018;13:40–8.
23. Weisenberger DJ, Siegmund KD, Campman N, etal. CpG island
methylator phenotype underlies sporadic microsatellite instability
and is tightly associated with BRAF mutation in colorectal cancer.
Nat Genet. 2006;38:787–93.
24. Rex DK, Shaukat A, Wallace MB. Optimal management of
malignant polyps, from endoscopic assessment and resection to decisions about surgery. Clin Gastroenterol Hepatol.
2019;17:1428–37.
25. Compton CC.Key issues in reporting common cancer specimens:
problems in pathologic staging of colon cancer. Arch Pathol Lab
Med. 2006;130:318–24.
26. Moss A, Bourke MJ, Williams SJ, et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer
from advanced colonic mucosal neoplasia. Gastroenterology.
2011;140:1909–18.
27. Lopez A, Bouvier AM, Jooste V, etal. Outcomes following polypectomy for malignant colorectala polyps are similar to those
following surgery in the general population. Gut. 2019;68:111–7.
28. The Paris endoscopic classication for supercial neoplastic
lesions: esophagus, stomach, and colon: November 30 to December
1, 2002. Gastrointest Endosc. 2003;58(6 suppl):S3–S43.
29. Endoscopic Classication Review Group. Update on the Paris
classication of supercial neoplastic lesions in the digestive
tract. Endoscopy. 2005;37:570–8.
30. Okamoto T, Tanaka S, Haruma K, etal. Clinicopathologic evaluation on colorectal laterally spreading tumor (LST). Nihon
Shokakibyo Gakkai Zasshi. 1996;93:83–9.
31. Soetikno RM, Kaltenbach T, Rouse RV, etal. Prevalence of nonpolypoid (at and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA. 2008;299:1027–35.
32. Rembacken BJ, Fujii T, Cairns A, etal. Flat and depressed colonic
neoplasms: a prospective study of 1000 colonoscopies in the
UK.Lancet. 2000;355:1211–4.
33. Kudo S, Lambert R, Allen JL, et al. Nonpolypoid neoplastic
lesions of the colorectal mucosa. Gastrointest Endosc. 2008;68(4
Suppl):S3–S47.
34. Burgess NG, Hourigan LF, Zanati SA, et al. Risk stratication
for covert invasive cancer among patients referred for colonic
endoscopic mucosal resection: a large multicenter cohort.
Gastroenterology. 2017;153:732–42.
35. Kudo S, Hirota S, Nakajima T, etal. Colorectal tumours and pit
pattern. J Clin Pathol. 1994;47:880–5.
36. Togashi K, Konishi F, Ishizuka T, et al. Efcacy of magnifying endoscopy in the differential diagnosis of neoplastic and
non-neoplastic polyps of the large bowel. Dis Colon Rectum.
1999;42:1602–8.
37. Tung SY, Wu CS, Su MY.Magnifying colonoscopy in differentiating neoplastic from nonneoplastic colorectal lesions. Am J
Gastroenterol. 2001;96:2628–32.
38. Konishi K, Kaneko K, Kurahashi T, etal. A comparison of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal
polyps: a prospective study. Gastrointest Endosc. 2003;57:48–53.
39. Draganov PV, Gotoda T, Yang D. Advanced techniques for
endoscopic resection in the GI tract. 1st ed. Thorofare: Slack
Incorporated; 2019. p.26.
40. Sano Y, Horimatsu T, Fu KI, et al. Magnifying observation of
microvascular architecture of colorectal lesions using a narrow
band imaging system. Dig Endosc. 2006;18:S44–51.
41. Sano Y, Ikematsu H, Fu KI, et al. Meshed capillary vessels by
use of narrow-band imaging for differential diagnosis of small
colorectal polyps. Gastrointest Endosc. 2009;69:278–83.
42. Katagiri A, Fu KI, Sano Y, etal. Narrow band imaging with magnifying colonoscopy as a diagnostic tool for predicting the histology of early colorectal neoplasia. Aliment Pharmacol Ther.
2008;27:1269–74.
43. Ikematsu H, Matsuda T, Emura F, etal. Efcacy of capillary pattern type IIIA/IIIB by magnifying narrow band imaging for estimating depth of invasion of early colorectal neoplasms. BMC
Gastroenterol. 2010;10:33.
44. Sano Y, Tanaka S, Kudo S, et al. Narrow-band imaging
(NBI) magnifying endoscopic classication of colorectal
tumors proposed by the Japan NBI Expert Team. Dig Endosc.
2016;28:526–33.
45. Hewett DG, Kaltenbach T, Sano Y, etal. Validation of a simple
classication system for endoscopic diagnosis of small colorectal polyps using narrow-band imaging. Gastroenterology.
2012;143:599–607.
46. Puig I, Lopez-Ceron M, Arnau A, etal. Accuracy of the narrowband imaging international colorectal endoscopic classication
system in identication of deep invasion in colorectal polyps.
Gastroenterology. 2019;156:75–87.
47. Haggitt RC, Glotzbach RE, Soffer EE, et al. Prognostic factors
in colorectal carcinomas arising in adenomas: implications for
lesions removed by endoscopic polypectomy. Gastroenterology.
1985;89:328–36.
48. Kudo S.Endoscopic mucosal resection of at and depressed types
of early colorectal cancer. Endoscopy. 1993;25:455–61.
49. Kikuchi R, Takano M, Takagi K, etal. Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.
Dis Colon Rectum. 1995;38:1286–95.
50. Nascimbeni R, Burgart LJ, Nivatvongs S, et al. Risk of lymph
node metastasis in T1 carcinoma of the colon and rectum. Dis
Colon Rectum. 2002;45:200–6.