Introduction
Traditionally, patients with large colonic polyps have been referred for surgery,
which carries significant morbidity and mortality [1]
[2]. Even with the advent of endoscopic mucosal resection (EMR) as a safe and effective
treatment of such large lesions, the referral rate for surgery remains high [3]
[4]
[5]. Cost analyses demonstrated that EMR is cheaper than endoscopic submucosal dissection
and surgery [6]
[7]
[8]
[9].
One of the arguments against EMR of large polyps (unlike surgery and endoscopic submucosal
dissection) is a high rate of both incomplete resection and local recurrence. Most
studies demonstrated local recurrence rates of 15 % to 30 % in patients with large
colonic polyps [10]
[11]
[12]. Several polyp characteristics are linked with an increased risk of local recurrence
after EMR, such as lesion size and morphology, prior intervention, presence of high-grade
dysplasia (HGD), EMR technique, and margin positivity [13]
[14]
[15]. Nonetheless, whether ancillary maneuvers such as systematic observation of the
EMR site with a cap fitted colonoscope followed by ablation of the edge with APC can
lead to a decrease in the recurrence rate has yet to be well studied.
Previously, we reported on our preliminary experience in performing EMR for complex
colon polyps as an alternative to surgery using a standardized protocol since 2009
[16]. As part of that protocol, after documenting absence of macroscopic disease at the
EMR edge and base using a cap-fitted endoscope, we applied argon plasma coagulation
(APC) to the resection site. Our aim was to determine the impact of APC of the EMR
edge on local colonic adenoma recurrence.
Patients and methods
Patients
This was a retrospective study of consecutive patients with large laterally spreading
tumors (LSTs) of the colon (≥ 20 mm) who underwent EMR using a standardized protocol
from January 2009 to August 2018 at The University of Texas MD Anderson Cancer Center.
Ethical approval of this study was obtained from the MD Anderson Institutional Review
Board. Reasons for exclusion included patients with pedunculated polyps and sessile
tumors, confirmed cancers that that were referred to us as benign tumors, lesions
with extensive tethering to the colon wall, and lesions that could not be resected
due to challenging endoscopic access.
Procedures
One endoscopist performed all the steps in the procedure: clinic visits to counsel
the patients, with education about EMR using a dedicated YouTube channel; EMR following
a standard protocol; discharge of patients after standard recovery; close follow-up
examination with email communication during the first 5 days after the procedure;
and surveillance colonoscopy at 6 and 18 months after EMR [16].
Patients with a Boston Bowel Preparation Scale score of 8 or 9 underwent EMR using
a high-definition cap-fitted endoscope (CF-H180AL/I, CF-Q180AL/I, or CF-HQ190; Olympus,
Center Valley, Pennsylvania, United States) and lift-and-cut technique under sedation
or anesthesia. Prior to the start of the resection, each lesion was examined carefully
for features of deep submucosal cancer (Narrow Band Imaging International Colorectal
Endoscopic classification III). Resection was not performed in patients with obvious
cancerous lesions, even though they were designated as benign at referral. In cases
where EMR is forecasted to be technically difficult, a colorectal surgeon was consulted
prior to the procedure to assess risk. Saline with either indigo carmine or methylene
blue with or without epinephrine was used for dynamic submucosal injection. Snare
resection was performed using a microprocessor-controlled generator (ENDO CUT Q; Erbe
USA, Marietta, Ga [effect 3; duration, setting 1; interval, settings 3–5]). After
each resection, the resection base was examined before proceeding with the next resection.
Additional fluid was injected if necessary before proceeding with subsequent resections.
Bleeding during the procedure was controlled with hemostatic forceps (Olympus America,
Melville, New York, United States [soft coagulation, effect 4, 60–80 W]). The process
was repeated until all visible tissue was removed. Cold biopsy avulsion was used to
remove tethered polyp (2009 to 2014); hot biopsy avulsion (ENDO CUT I [effect 1; duration,
setting 1; interval, setting 1]) was used to remove small amounts of neoplastic tissue
that could not be removed with a snare resection (2014 to 2018).
Completeness of resection was documented by systematically inspecting the entire edge
with the endoscope cap touching the edge and taking photos of overlapping areas. This
was followed by systematic examination of the resection base. Completeness of resection
was defined as absence of any visible polyp in the resection base and edge and documentation
of a round mucosal pit pattern at the resection edge.
APC was applied starting at one point on the resection edge and going around it to
create a deep burn with brown discoloration of the entire edge using forced coagulation
at 30 to 35 W and 0.8 L per minute flow. In addition, APC was applied to any areas
in the resection base from which tiny residual polyp was removed using biopsy forceps.
Once again, photos of overlapping areas of the ablated resection edge around the site
were taken. Injection of tattoo (SPOT; GI Supply, Mechanicsburg, Pennsylvania, United
States) was applied for lesions between proximal ascending colon and rectosigmoid
colon. Attempts were made to close any EMR defects with clips.
Surveillance
Patients were instructed to send messages to the endoscopist via e-mail or an electronic
health record communication tool for the first 5 days after EMR to provide information
about their progress; some patients had the endoscopist’s cell phone number and could
call if they experienced any complications. On days 5 to 7, the endoscopist contacted
the patients by phone to inform them of their pathology results and inquire about
any complications. Surveillance colonoscopy was performed at 6 and 18 months after
EMR by the same endoscopist in the majority of cases. During surveillance colonoscopy,
the EMR scar was carefully examined using white light and narrow band imaging (NBI)as
well as near-focus function of the endoscope and multiple photos of the scar site
were taken. Biopsies of the EMR scars were routinely done except in patients with
smooth scars and round mucosal pit pattern. Recurrence of adenoma identified during
surveillance was managed using cold or hot biopsy avulsion followed by APC and clip
closure.
Data collection and analysis
Patient data were collected retrospectively from medical charts and endoscopy reports
using natural language processing [17]. Collected variables pertaining to medical history included age, race, sex, body
mass index, and use of anticoagulation and antiplatelet therapy before EMR. Also,
whether the patient was self-referred for EMR, was referred by an endoscopist, or
had EMR during the initial screening procedure was recorded.
At the time of EMR, endoscopic data were entered prospectively into a structured and
formatted endoscopy report (EndoWorks; Olympus, and later Provation, Minneapolis,
Minn). Photographic documentation of the endoscopic procedure with the EMR phases
was done with a minimum of 20 photos for each lesion (maximum, 71 photos). Moreover,
the majority of resections in our study were videotaped and posted on YouTube for
educational purposes. Follow-up endoscopy was performed with imaging of the site of
the prior EMR scar.
The number of polyps is equal to the number of patients, as we accounted for the largest
lesion. Data relating to polyps were extracted from endoscopy and histopathology reports.
Collected variables were: 1) the location, size, and morphology of the polyp; 2) ease
of accessing the polyp endoscopically; 3) presence of HGD; 4) local polyp recurrence;
and 5) complications.
Local recurrence was defined as residual polyp at the site of the original resection
(histologically confirmed as adenoma) at the time of surveillance endoscopy. Clean,
flat scars with no visible residual polyp upon white light, NBI, and near-focus examination
were considered to be free from recurrence; biopsies were not routinely done to document
clean scars without recurrent polyps [18]. Patients in whom no scar was visible despite careful examination of the area were
also considered to be free of recurrence.
Complications were defined as those that required hospitalization, blood or blood
product transfusions, endoscopic intervention, or surgery for management of abdominal
pain, bleeding, or perforation.
Study endpoint
The primary endpoint was presence of endoscopically visible residual neoplastic tissue
at the resection site that was histologically confirmed as adenoma at first surveillance
endoscopy.
Data analysis
Categorical variables were summarized using frequencies and percentages. Continuous
variables were summarized using Median values and interquartile ranges (IQRs). Logistic
regression analysis was performed to assess the impact of patient and procedure factors
on recurrence. P ≤ 0.05 was considered statistically significant. Statistical analysis was performed
using the SAS software program (version 9.4; SAS Institute, Cary, North Carolina,
United States).
Results
Patients
Two hundred and forty-six consecutive patients with ≥ 20 mm LST who underwent EMR
followed by surveillance colonoscopy to check the scar site for recurrence comprise
the study cohort. One hundred thirty-one patients were female (53 %). Most of the
patients were white (197 [80 %]), and the patients’ Median age was 64 years (IQR,
55–70 years). Patient and polyp characteristics are summarized in [Table 1].
Table 1
Patient and polyp characteristics.
Characteristic
|
Number of patients (%)
|
Median age, years (IQR)
|
64 (55–70)
|
Female sex
|
131 (53)
|
Race
|
|
197 (80)
|
|
21 (9)
|
|
8 (3)
|
|
6 (2)
|
|
14 (6)
|
Referral type
|
|
34 (14)
|
|
212 (86)
|
Anesthesia type
|
|
|
97 (39)
|
|
78 (32)
|
|
71 (29)
|
Endoscopic access
|
|
160 (65)
|
|
86 (35)
|
Polyp location
|
|
65 (26)
|
|
81 (33)
|
|
50 (20)
|
|
18 (7)
|
|
14 (6)
|
|
18 (7)
|
Median polyp size, mm (IQR)
|
35 (30–45)
|
EMR type
|
|
172 (70)
|
|
74 (30)
|
Polyp pathology
|
|
79 (32)
|
|
77 (31)
|
|
67 (27)
|
|
14 (6)
|
|
9 (4)
|
HGD
|
81 (33)
|
Complications
|
10 (4)
|
IQR, interquartile range; EMR, endoscopic mucosal resection; HGD, high-grade dysplasia
EMR of polyps
Median size of polyps was 35 mm (IQR, 30–45 mm). Most of the polyps were located in
the right colon (189 [77 %]). The endoscopist removed 172 polyps (70 %) using piecemeal
EMR, whereas the 74 (30 %) were removed using en bloc EMR. Median total EMR procedure
time was 60 minutes (IQR, 47–79 minutes).
EMR complications
Eight patients developed delayed bleeding, one patient developed perforation, two
patients required hospitalization, and none required emergency surgery or died from
the procedure.
Seventeen patients did not have clip closure of the lesion edges after successful
EMR; one (6 %) of them developed excessive bleeding after EMR. Among patients who
had clip closure (n = 229), nine patients had adverse events: seven (3 %) had postprocedural
bleeding, six of these had spontaneous resolution of the bleeding and only one case
required clip replacement; one had a small perforation that was closed successfully
during the procedure; and one experienced respiratory difficulty after the procedure.
Two of the patients that had post-EMR bleeding required hospitalization.
Pathology of polyps
Pathology of the 246 lesions included the following: 79 polyps (32 %) were tubular
adenomas, 77 (31 %) were tubulovillous adenomas, 14 (6 %) were villous adenomas, 67
(27 %) were serrated adenomas, and 9 (4 %) were adenocarcinoma. Eighty-one polyps
(33 %) had evidence of HGD in addition to the adenomatous features.
Local recurrence
All of the patients in our cohort underwent follow-up colonoscopy at 6 months after
EMR. The physician found the EMR scar and performed biopsy analysis of it in 190 patients.
In 30 patients with a smooth EMR scar and normal round mucosal pit pattern, the biopsies
were deferred. Twenty-six patients had no detectable scar from the initial EMR. Eleven
patients (5 %) had residual tumor at the resection site at the 6-month follow-up colonoscopy
([Fig. 1]).
Fig. 1 Flowchart of patients with > 20-mm colon LSTs who underwent EMR followed by argon
plasma coagulation.
Characteristics of the original polyps in patients who had local recurrence are listed
in [Table 2]. All patients who had recurrences had undergone piecemeal EMR. Two of the patients
underwent previous attempts at polyp resection that led to tethering of the polyp
to the colon wall. Eight of these lesions were in the right colon, and three were
in the rectum. Four of the patients who had local recurrence had HGD in the original
polyp. No complications occurred during removal of the initial lesion in these 11
patients. Results of logistic regression analysis performed to assess the association
of patient and polyp characteristics with recurrence revealed that only older age
was associated with increased risk of local recurrence (odds ratio, 1.09 [95 % confidence
interval, 1.02–1.17]; P = .013).
Table 2
Characteristics of the original polyps in patients who had local recurrence (n = 11).
Characteristic
|
Number of patients (%)
|
Median age, years (IQR)
|
73 (68–75)
|
Piecemeal EMR
|
11 (100)
|
Tethering to the colon wall
|
2 (18)
|
Median time of procedure, minutes (IQR)
|
63 (41–80)
|
Endoscopic access
|
|
6 (55)
|
|
5 (46)
|
Paris classification
|
|
9 (82)
|
|
2 (18)
|
Polyp location
|
|
8 (73)
|
|
3 (27)
|
Median polyp size, mm (IQR)
|
35 (25–50)
|
Polyp pathology
|
|
5 (46)
|
|
3 (27)
|
|
0 (0)
|
|
3 (27)
|
|
0 (0)
|
HGD
|
4 (36)
|
IQR, interquartile range; EMR, endoscopic submucosal resection; HGD, high-grade dysplasia
Features of locally recurrent lesions
Recurrent lesions were visible in 10 of 11 patients who had local recurrence. The
sizes of the visible recurrent lesions ranged from 3 to 4 mm. Only one lesion required
repeat EMR. Among the patients who had local recurrence, 10 had tubular adenoma and
one had serrated adenoma. HGD was present in two patients.
Discussion
This study demonstrated that the local colon adenoma recurrence rate in our cohort
of patients with ≥ 20-mm colon LSTs managed using cap-fitted colonoscopy with EMR
and ablation of the resection edge with APC was low (4.5 %). This adenoma recurrence
rate was much lower than 16.0 % to 32 % reported in the literature on traditional
EMR for non-pedunculated polyps ([Table 3]) [3]
[10]
[12]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32].
Table 3
Summary of colon EMR studies for non-pedunculated lesions.
Study
|
Country
|
Size of polyp (mm)
|
Total no. of patients
|
Piecemeal EMR
|
No. of patients with follow-up
|
Recurrence (%)
|
Moss et al. (2011) [3]
|
Australia
|
Median, 30 (IQR, 25–40)
|
479
|
479
|
328
|
67 (20.4 %)
|
Buchner et al. (2012) [27]
|
USA
|
mean, 23 (SD, 13)
|
274
|
132
|
135
|
36 (27 %)
|
Carvalho et al. (2013) [28]
|
Portugal
|
Median, 30 (IQR, 20–35)
|
71
|
71
|
71
|
16 (22.2 %)
|
Knabe et al. (2014) [12]
|
Germany
|
Mean, 33 (range, 20–100)
|
252
|
223
|
183
|
58 (31.7 %)
|
Maquire et al. (2014) [29]
|
USA
|
Mean, 28 (SD, 11)
|
231
|
231
|
160
|
38 (23.8 %)
|
Moss et al. (2015) [10]
|
Australia
|
Median, 30 (IQR, 25–40)
|
1,134
|
–
|
799
|
128 (16.0 %)
|
Sidhu et al. (2016) [30]
|
Australia
|
Median, 35 (IQR, 25–45)
|
2,675
|
2,308
|
1,910
|
312 (16.3 %)
|
Zhan et al. (2016) [31]
|
Germany
|
Mean, 37.2 (SD, 19.6)
|
129
|
88
|
129
|
34 (26.3 %)
|
Tate et al. (2017) [24]
|
Australia
|
Median, 35 (IQR, 30–45)
|
1,178
|
1,178
|
1,178
|
228 (19.4 %)
|
Barosa et al. (2018) [32]
|
UK
|
Mean, 35 (SD, 17)
|
316
|
–
|
316
|
65 (20.6 %)
|
Current study
|
USA
|
Median, 35 (IQR, 30–45)
|
246
|
172
|
246
|
11 (4.5 %)
|
Our large cohort study of 246 patients who underwent APC supports the observations
in a randomized controlled trial (RCT) of 21 patients with > 1.5-cm sessile polyps
demonstrating that APC of a resection edge free from macroscopic disease reduces local
recurrence rate; the recurrence rate in the APC treated group was 10 % [19]. We postulate that routine APC ablation of EMR defects using cap fitted colonoscope
removes microscopic residual adenoma at the resection edge that is not identified
by the endoscopist as shown previously, [20] which accounts for the low recurrence rate in our study (4.5 %). A recent RCT demonstrated
significant reduction in adenoma recurrence in patients who underwent ablation of
post-EMR defects using snare tip soft coagulation [21]. This method of snare tip coagulation is an attractive option given its simplicity
and ready availability, with no additional costs incurred. However, APC being a non-contact
modality offers the advantage of ablating areas that may be difficult to do with snare
tip coagulation. Currently, no RCTs in the literature have compared use of different
ablation techniques to reduce polyp recurrence after EMR.
Concerns about use of APC include variable arching of the electrosurgical current
from the catheter to the tissue, with the potential for excessive injury that may
predispose patients to complications such as bleeding and perforation, resulting in
a lack of the desired effect [22]
[23]. However, in our study, we have not observed any complication related to the application
of APC such as perforation or postpolypectomy syndrome. We postulate that using a
cap at the end of the endoscope and keeping the tip of the cap just above the tissue
allows for fixing the distance from the APC catheter to the tissue, thereby minimizing
variable arching of the electrosurgical current from the catheter to the tissue.
Recently, researchers developed and validated several scoring systems for local recurrence
of large polyps [14]
[15]
[24]. HGD, size of the lesion, number of polyps, and occurrence of bleeding during EMR
are independent predictors of recurrence in those systems. In the current study, we
did not find an association between these factors and recurrence. We attribute this
to the small number of local recurrences in our cohort. In contrast, we did observe
a significant association between older patient age and local recurrence (P = .004). This finding is similar to that reported by Pommergaard et al [25]. Also, authors reported that piecemeal EMR was associated with a greater risk of
local recurrence than was en bloc EMR [11]
[26]. However, due to the small number of local recurrences in our study, all of which
occurred after piecemeal EMR, we were not able to draw any meaningful conclusions.
Our study had notable strengths. For example, one endoscopist performed all of the
EMRs following the same protocol. This prevented discrepancy in findings that can
occur with use of more than one endoscopist. In addition, we included only patients
with large polyps to decrease the effect of polyp size as a major confounding factor.
Furthermore, the endoscopist communicated via email or telephone to assess patients
for complications after EMR. Finally, the structured form used to report endoscopy
and EMR details prevents the inherent limitations of the retrospective nature of our
study.
Our study did have limitations. First, it was a single-center study. Second, although
we had a relatively large sample size, the small number of patients with local recurrence
limited our ability to perform more sophisticated analysis to assess the effect of
several factors on the local adenoma recurrence rate. Performance of follow-up endoscopic
assessment by a single endoscopist could have led to inherent bias. To prevent this,
the endoscopist performed extensive photographic documentation of the lesions and
biopsy samples to evaluate the EMR sites.
Conclusion
In conclusion, we found that using a cap-fitted endoscope for systematic examination
of the EMR site for any macroscopic polyp and performing APC at the resection edges
led to a substantial decrease in the local recurrence rate in patients with large
colon polyps after EMR.