Introduction
Endoscopic removal of neoplasia in the colon and rectum has been proven to reduce
incidence and mortality of colorectal cancer (CRC) [1]. It is generally held that pedunculated colorectal lesions can be resected with
snare polypectomy irrespective of polyp size [2]. Non-pedunculated polyps in the colon and rectum are more challenging to remove
and endoscopic mucosal resection (EMR) has become standard method for resecting flat
and sessile lesions either en bloc (lesion size < 2 cm) or piece meal (lesions size
> 2 cm) [3]
[4]
[5]. It is well known that risk of submucosal invasive cancer increases in parallel
to polyp size. In fact, incidence of malignant infiltration in colorectal lesions
larger than 2 cm is higher than 10 % [6]
[7]
[8]
[9]. Piecemeal resection is not only associated with a risk of incomplete resection
and tumor recurrence but also a non-conclusive pathological evaluation in terms of
tumor resection margins, which in cases of submucosal invasive cancer can result in
unnecessary surgery [10]. Knowing that pre-resection diagnosis of submucosal invasion is notoriously difficult,
en bloc resection is recommended for removal of large colorectal lesions [11]
[12]
[13].
Endoscopic submucosal dissection (ESD) was developed in Japan to avoid piecemeal resection
and allows en bloc resection of large gastric and colorectal neoplasias. As of today,
ESD has been implemented as standard treatment of large gastrointestinal lesions in
many Asian countries and the efficacy has been well documented in numerous reports
[6]
[11]
[14]
[15]. However, dissemination of ESD in western countries has been slow and only a handful
centers in Europe have established comprehensive and proficient ESD programs. Major
challenges for implementing ESD in western countries comprise a long learning curve,
high risk of complications, lack of structured training programs, few suitable starting
cases in the stomach, and lack of experts [16]
[17]
[18]
[19]
[20]
[21]. Although there has been an increase in the number of published reports on colorectal
ESD from western countries the majority of these are relatively small containing less
than 100 cases with few exceptions [8]
[9]
[22]
[23].
Herein, we present the largest material on colorectal ESD in the west, to our knowledge,
including outcome, complications and learning curve.
Patients and methods
Patients and tumors
From January 2013 to November 2017, 872 patients with large (> 2 cm), non-pedunculated
or recurrent colorectal lesions referred for ESD underwent endoscopic resection at
our tertiary colonoscopy center at Skåne University Hospital in Malmö, Sweden. Lesions
were thoroughly investigated by use of topical administration of 0.4 % indigo carmine
and narrowband imaging (NBI), in addition to white light to detect signs of invasive
cancer and to assess the most optimal endoscopic resection technique. In general,
EMR was selected for lesions smaller than 3 cm with low suspicion of submucosal invasion.
ESD was chosen for lesions larger than 3 cm or lesions with suspicion of submucosal
invasion. Five hundred and thirty-five lesions were resected with either EMR or underwater
EMR and 337 lesions were resected with ESD. We excluded all 36 malignant lesions from
this study solely since they have been reported previously [24]. In the current study, we retrospectively included and reviewed 301 colorectal ESD
cases without submucosal invasion. Paris classification was used to define macroscopic
appearance of the tumors [25]. Localization of lesions was divided as follows: rectum, distal colon (sigmoid and
descending colon) and proximal colon (cecum, ascending and transverse colon).
Colorectal ESD
All patients underwent colonic cleansing with polyethylene glycol and were given scopolamine
butyl bromide or glucagon to reduce bowel movements as well as sedatives and analgesic.
Conventional video endoscope (GIF-H180 J and CF-H180AI, Olympus, Hamburg, Germany)
with a disposable distal hood (D-201-11804 or D-201-15004, Olympus) attached to the
tip of the endoscope was employed. Carbon dioxide was utilized for insufflation. For
electrical cutting and coagulation VIO 300 D (ERBE Elektromedizin, Tübingen, Germany)
was used as a power source (Cut: Endocut 1 effect 2; Forced coagulation: Effect 2,
40W; Soft coagulation: Effect 5, 60 W). ESD was carried out in a standardized manner
using a Flush-knife (Fujifilm Europe GmbH, Düsseldorf, Germany) connected to a water
jet pump, as described in detail previously ([Fig. 1]) [26]. Hyaluronate sodium solution (0.4 %, Sigmavisc, Hyaltech Ltd, Livingston, UK) was
used to lift the mucosal layer. Hemostatic forceps (Coagrasper, FD-411UR, Olympus)
was used to prevent and treat bleeding. Resected specimens were retrieved using grasping
forceps (FG-47L-1; Olympus) or a retrieval device (Roth Net, US Endoscopy, Mentor
Ohio, United States). Specimens were measured after being pinned onto a hard plate
and then submerged in 10 % formalin. Lesion area was calculated using the formula
A = abπ, where a is half the diameter of the major diameter and b is half the diameter
of the minor diameter, which is applicable for both circular and ellipse shaped objects.
Procedure time was defined as the time from incision with the Flush-knife until complete
removal of the lesion. Proficiency (resection speed), defined as square centimeter
resected per hour (cm2/h), was calculated. Main outcomes were en bloc and R0 resection rates as well as
proficiency and recurrence. The following variables were tested with univariate and
multivariate analysis for possible impact on main outcomes: lesion localization, area,
Paris type and histologic grade.
Fig. 1 ESD procedure. a A large (90x60 mm), flat (Paris classification IIa), sigmoid lesion as seen with normal
endoscopic view with indigo carmine staining prior to resection. b The post-ESD wound covering 80 % of the circumference. c The specimen, resected en bloc, pinned on to a hard plate.
ESD training and learning curve
All procedures were performed by a single experienced colonoscopist (HT) who prior
to the study period learned ESD by attending ESD tutorial courses, undertaking animal
ex vivo training in Europe and Japan and performing ESD under supervision of Japanese
experts. All ESD procedures were grouped consecutively in five chronological time
periods with similar numbers of procedures in each period as follows: period 1 (P1)
60 cases, period 2 (P2) 60 cases, period 3 (P3) 60 cases, period 4 (P4) 60 cases,
period 5 (P5) 61 cases. This division was decided prior to data processing and statistical
computations to minimize bias.
Histological evaluation
Resected specimens were sectioned serially at 3-mm intervals and embedded for histological
examination. The Vienna classification of gastrointestinal neoplasia was used to classify
the colorectal neoplasms [27]. Resections were defined as follows; R0 tumor-free vertical and lateral margins,
R1 evidence of tumor cells on the vertical or lateral margins, RX margins could not
be reliably assessed.
Complications and post-ESD management
All patients’ medical records were scrutinized to detect any complications up to 30
days after ESD. The Clavien-Dindo classification of surgical complications was adopted
[28]. Complications were classified as immediate (detected during the procedure) or delayed
(detected after ESD). Perforation was defined as defects with visible omentum or other
tissue outside the muscle layer detected during the procedure or as free air in the
abdomen on image studies or apparent during emergency surgery. Bleeding was defined
as immediate hemorrhage causing abortion of the procedure or clinical evidence within
14 days of the procedure. Follow-up was determined by the referring physician, supported
by European Society of Gastrointestinal Endoscopy (ESGE) guidelines taking patient
wish, age and comorbidity into account [29].
Post-procedural care and need for hospitalization
Need for hospitalization was determined prior to ESD considering lesion location and
size as well as patient age and comorbidity. During the early periods, patients were
in general hospitalized if lesions were larger than 5 cm and/or based on proximal
location and/or high age and comorbidities. During the later periods, individuals
with rectal lesions and distal colonic lesions were managed as outpatients regardless
of lesion size. Patients scheduled as outpatients were hospitalized if needed as evaluated
on a case to case basis.
Statistics and ethics
Data are given as median and range. All data analysis was conducted with SPSS version
22.0 (SPSS Inc., Chicago, Illinois, United States). Categorical variables were compared
with the Chi-squared test. Linear by linear association was used to evaluate changes
in categorical parameters over time. Continuous variables were compared using the
one-way Annova test with the Bonferroni-Holm correction. Univariate and multivariate
regression analysis were used to determine predictors of main outcomes. P values < 0.05
were considered significant. All patients received detailed information prior to the
procedure explaining risks of complications and possibility of additional surgery.
Informed consent was obtained. Approval by the Regional Ethical Review Board, Lund
University (2017/1) was granted prior to the study and ethical principles of the Declaration
of Helsinki were followed. All data were coded and patient anonymity was guaranteed.
Results
Patient and tumor characteristics
Between January 2013 and November 2017 (59 months), 301 colorectal ESD cases with
invasion limited to the mucosa were included and reviewed. 284 cases were large (> 2 cm)
non-pedunculated lesions and 17 cases were recurrences. Median age was 72 years (range
35 – 96) and consisted of 159 males (53 %) and 142 females (47 %). One hundred seventy-three
lesions (57 %) were located in the rectum and 128 (43 %) were located in the colon
([Table 1]). Median size was 4 cm (range 1 – 12.5) and area 11 cm2 (range 0.8 – 78.5). Lesion type according to Paris classification and histology are
depicted in [Table 1].
Table 1
Patient and lesion characteristics.
|
P1
|
P2
|
P3
|
P4
|
P5
|
Total
|
|
Number of cases
Residual lesions
|
60
8
|
60
4
|
60
1
|
60
1
|
61
3
|
301
17
|
|
Age
|
73
(46 – 96)
|
77
(40 – 89)
|
72
(40 – 90)
|
69
(35 – 90)
|
68
(37 – 89)
|
72
(35 – 96)
|
|
Gender
Female
Male
|
25
35
|
27
33
|
34
26
|
25
35
|
31
30
|
142
159
|
|
Localization
Rectum
Distal colon
Proximal colon
|
30
14
16
|
32
16
12
|
33
14
13
|
39
12
9
|
39
16
6
|
173 (57 %)
72 (24 %)
56 (19 %)
|
|
Paris type
Is
Iia
IIa/Is
|
27
30
3
|
22
36
2
|
35
23
2
|
31
24
5
|
33
24
4
|
148
137
16
|
|
Histology
Serrated
Adenoma LGD[1]
Adenoma HGD[2]
|
1
40
19
|
1
38
21
|
–
43
17
|
1
43
16
|
2
38
21
|
5
202
94
|
|
Lesion size
Diameter (cm)
|
3
(1.5 – 8)
|
4
(1 – 8)
|
4
(1.5 – 10)
|
5
(2 – 11)
|
5
(2 – 12.5)
|
4
(1 – 12.5)
|
|
Area (cm2)
|
6.3
(1.1 – 44)
|
9.4
(0.8 – 38)
|
10.6
(1.1 – 56)
|
13.9
(2.5 – 69)
|
14.1
(3.1 – 78)
|
11
(0.8 – 78)
|
1 LGD, low-grade dysplasia
2 HGD, high-grade dysplasia
ESD performance
En bloc resection was achieved in 241 out of 301 cases, amounting to an en bloc resection
rate of 80 % for the entire period ([Table 2]). Piecemeal resection was performed in 58 cases (19 %) and ESD was incomplete and
aborted in two cases (1 %) ([Table 2]). R0 resection was accomplished in 207 cases (69 %) and RX and R1 were attained
in 83 (27 %) and 11 (4 %) cases, respectively. Median procedural time was 98 min (range
10 – 588) and median proficiency was 7.2 cm2/h (range 0.6 – 56.4) ([Table 2]). En bloc and R0 resection rates according to lesion localization was as follows:
rectum 87 % and 74 %, distal colon 83 % and 64 %, proximal colon 54 % and 59 %, respectively
([Table 3]).
Table 2
ESD outcome.
|
P1
|
P2
|
P3
|
P4
|
P5
|
Total
|
|
Number of cases
|
60
|
60
|
60
|
60
|
61
|
301
|
|
Resection
En bloc
Piecemeal
Incomplete
|
36 (60 %)
22 (37 %)
2 (3 %)
|
45 (75 %)
15 (25 %)
–
|
49 (82 %)
11 (18 %)
–
|
51 (85 %)
9 (15 %)
–
|
60 (98 %)
1 (3 %)
–
|
241 (80 %)
58 (19 %)
2 (1 %)
|
|
R0
R1
RX
|
36 (60 %)
3 (5 %)
21 (35 %)
|
37 (62 %)
–
23 (38 %)
|
46 (76 %)
1 (2 %)
13 (22 %)
|
39 (65 %)
4 (7 %)
17 (28 %)
|
49 (80 %)
3 (5 %)
9 (15 %)
|
207 (69 %)
11 (4 %)
83 (27 %)
|
|
Procedural time (min)
|
133
(19 – 588)
|
122
(28 – 260)
|
75
(10 – 300)
|
78
(16 – 362)
|
91
(32 – 312)
|
98
(10 – 588)
|
|
Proficiency
(cm2/h)
|
3.6
(2.4 – 10)
|
5.4
(0.6 – 26)
|
9.6
(0.6 – 31)
|
10.2
(2.4 – 35)
|
10.8
(2.4 – 56)
|
7.2
(0.6 – 56)
|
|
Hospitalised
Median stay
|
39 (66 %)
1 (1 – 18)
|
26 (43 %)
1 (1 – 5)
|
20 (33 %)
1 (1 – 4)
|
14 (23 %)
1 (1 – 103)
|
14 (23 %)
1 (1 – 6)
|
113 (38 %)
1 (1 – 103)
|
Table 3
ESD outcome according to location.
|
En bloc
|
R0
|
Proficiency(cm2/h)
|
Perforation
|
ComplicationBleeding
|
Total
|
Recurrence
|
|
Rectum
N = 173
|
150
(87%)
|
128
(74 %)
|
9
0.6 – 56
|
3
(2 %)
|
3
(2 %)
|
6
(4 %)
|
4
(2 %)
|
|
Distal Colon
N = 72
|
61
(83 %)
|
46
(64 %)
|
7.2
0.6 – 30
|
4
(6 %)
|
1
(1 %)
|
5
(7 %)
|
2
(3 %)
|
|
Proximal Colon
N = 56
|
29
(54 %)
|
33
(59 %)
|
4.8
1.2 – 20
|
10
(18 %)
|
3
(5 %)
|
13
(23 %)
|
1
(2 %)
|
Learning curve
There was no significant difference in lesion location, macroscopic type and histopathology
of the lesions between the five periods. Median lesion area was significantly larger
in the fifth period (14.1 cm2) compared to the first period (6.3 cm2) (P < 0.001) ([Table 1]). In addition, ESD proficiency improved from P1 to P3 – 5 (P < 0.001) and from P2 to P3 – 5 (P < 0.001) but there was no significant improvement in proficiency after P3 ([Table 2]). Thus, after 120 ESD procedures (P1 + P2) no significant improvement in proficiency
was observed. The en bloc resection rate improved throughout the periods, starting
at 60 % during P1 and gradually increased to 98 % during P5 (P < 0.001) ([Table 2]). R0 resection rate also improved over periods with a temporary decrease between
P3 (76 %) and P4 (65 %), however improvement over time tested significant with linear
by linear association (P = 0.017) ([Table 2]). There was not any significant trend or difference regarding complication rate
between the study periods ([Table 4]). Notably, during P5 there was no significant difference in terms of en bloc and
R0 resection rates according to localization (rectum; en bloc 39/39 (100 %), R0 32/39
(82 %), distal colon; en bloc 15/16 (94 %) R0 12/16 (75 %), proximal colon; en bloc
5/6 (83 %), R0 5/6 (83 %).
Table 4
Complications and follow-up.
|
P1
|
P2
|
P3
|
P4
|
P5
|
Total
|
|
Number of cases
|
60
|
60
|
60
|
60
|
61
|
301
|
|
Immediate perforation
Surgery
|
2
1
|
5
–
|
2
–
|
–
–
|
3
–
|
12
1
|
|
Delayed perforation
Surgery
|
2
1
|
1
1
|
–
–
|
2
2
|
–
–
|
5
4
|
|
Immediate bleeding
Transfusion
Surgery
|
1
–
–
|
–
–
–
|
–
–
–
|
–
–
–
|
–
–
–
|
1
–
–
|
|
Delayed bleeding
Transfusion
Surgery
|
–
–
–
|
–
–
–
|
–
–
–
|
5
3
1
|
1
–
–
|
6
3
1
|
|
Follow-up
Months
Residual
Planned follow-up
|
40
22 (3 – 53)
3
–
|
50
18 (4 – 36)
2
–
|
49
8 (3 – 27)
1
1
|
43
9 (5 – 14)
1
7
|
22
6 (3 – 10)
–
39
|
204 (68 %)
12 (3 – 53)
7 (3 %)
47
|
It was found that lesion location affected en bloc and R0 resection rate and tested
significant with both univariate and multivariate analysis with higher rates in rectum
(P < 0.001) and lower rates in proximal colon (P < 0.001) ([Table 5]). Lesion location also had significant impact on both proficiency and complications
with higher proficiency and less complications in the rectum and lower proficiency
and more complications in the proximal colon with both univariate and multivariate
analysis ([Table 5]). Moreover, lesion area had negative impact on R0 resection rate testing significant
with multivariate analysis ([Table 5]). Lesion area had also a negative impact on proficiency, which was significant with
both univariate and multivariate analysis ([Table 5]). When tested with multivariate analysis, Paris type Is had positive impact (P = 0.004) and Paris type IIa had negative impact on proficiency (P = 0.017).
Table 5
Factors influencing outcome.
|
Variable
|
Univariate
|
Multivariate
|
|
Odds Ratio (95 % CI)
|
P-value
|
Odds Ratio (95 % CI)
|
P value
|
|
Impact on en bloc resection
|
|
Localization
Rectum
Distal colon
Proximal colon
|
2.70 (1.50 – 4.84)
1.48 (0.72 – 3.03)
0.19 (0.10 – 0.35)
|
0.001
0.286
< 0.001
|
2.64 (1.45 – 4.80)
1.55 (0.75 – 3.24)
0.17 (0.01 – 0.34)
|
0.001
0.24
0.001
|
|
Impact on R0 resection
|
|
Localization
Rectum
Distal colon
Proximal colon
|
1.91 (1.16 – 3.16)
0.82 (0.46 – 1.45)
0.47 (0.26 – 0.86)
|
0.010
0.489
0.013
|
2.14 (1.27 – 3.62)
0.75 (0.41 – 1.35)
0.44 (0.23 – 0.82)
|
0.004
0.332
0.011
|
|
Size (Area)
|
0.98 (0.97 – 1.00)
|
0.066
|
0.98 (0.96 – 1.00)
|
0.04
|
|
Impact on complications
|
|
Localization
Rectum
Distal colon
Proximal colon
|
0.21 (0.06 – 0.77)
2.11 (0.67 – 6.67)
2.88 (0.90 – 9.16)
|
0.010
0.195
0.063
|
0.20 (0.05 – 0.78)
2.30 (0.69 – 7.67)
3.18 (0.86 – 11.78)
|
0.020
0.175
0.083
|
|
Impact on proficiency
|
|
BETA[1]
|
P-value
|
BETA[1]
|
P value
|
|
Localization
Rectum
Distal colon
Proximal colon
|
0.223
–0.053
–0.224
|
< 0.001
0.364
< 0.001
|
0.113
–0.020
–0.124
|
0.025
0.695
0.015
|
|
Macroscopic type
Is
Iia
IIa/Is
|
0.060
–0.078
0.038
|
0.302
0.183
0.516
|
0.145
–0.121
–0.046
|
0.004
0.017
0.368
|
|
Size (Area)
|
0.526
|
< 0.001
|
0.532
|
< 0.001
|
1 BETA; standardized regression coefficient, applied for continues variables
Complications
Complications occurred in 24 patients (8 %) divided into 12 immediate perforations,
five delayed perforations, one immediate bleeding and six delayed bleeds ([Table 4]). Ten of the 11 patients who suffered from delayed complications were inpatients.
Thus, eight of the complications were detected during the hospital stay and three
patients with hematochezia returned to the emergency unit 2, 4 and 11 days after ESD.
We experienced two cases of incomplete resection. One was due to a perforation in
the left flexure, resulting in emergency surgery and the other was due to a bleed
during resection of a rectal lesion, which was managed by use of clips. In total,
six patients had emergency surgery (2 %, [Table 4]) due to a complication (Clavien-Dindo grade IIIb), one patient with a delayed cecal
perforation needed intensive care post-surgery (Clavien-Dindo grade IV). Complications
requiring surgical intervention were all located in the proximal colon (2 in cecum,
3 in ascending colon, 1 in transverse colon). The remaining 18 complications could
be managed conservatively with observation, fasting, antibiotics or blood transfusions
in selected cases (Clavien-Dindo II) ([Table 4]). Complications were more frequent in the proximal colon (13/56, 23 %) in comparison
to distal colon (5/72, 7 %) and rectum (6/173, 4 %) (P < 0.001) ([Table 3]).
Follow-up
Two hundred and four patients (68 %) were followed up endoscopically ([Table 4]). Median follow-up time was 13 months (range 3 – 53) revealing seven recurrences
(3 %) of which four had been resected by piecemeal technique (2 R1 and 2 RX). Two
recurrences had been resected en bloc (2 R0) and one occurred after an incomplete
resection in the rectum secondary to bleeding. Three of the recurrences were small
and removed by use of biopsy forceps or snare. One recurrence was successfully removed
by ESD. Transanal endoscopic microsurgery was used to remove two recurrences in the
rectum. One patient with recurrence in the sigmoid colon underwent surgery due to
difficult location. One stricture in the rectum was observed and treated successfully
with endoscopic dilatation. Forty-seven patients are waiting for endoscopic follow-up
([Table 4]). Three patients underwent resection during emergency surgery and the remaining
47 patients will not be followed up due to patient refusal, high age or aggravating
comorbidity.
Hospitalization
One hundred eighty-eight patients (62 %) were managed as outpatients and 113 patients
(38 %) were hospitalized ([Table 2]). Four of the hospitalized patients were scheduled as outpatients but admitted to
the hospital for observation after ESD. The rate of hospitalization was higher during
the first period (66 %) in comparison to the fifth period (23 %) (P < 0.001, [Table 2]). One patient with a cecal perforation had additional complications post-surgery
necessitating intensive care and represents the upper range of the hospital stay.
Discussion
ESD is standard treatment of early gastrointestinal neoplasia in Asian countries and
recommended by the 2015 ESGE guidelines as a first option to provide en bloc resection
with accurate pathologic staging of complex colorectal lesions with high suspicion
of limited submucosal invasion [10]. In spite of this, dissemination of ESD in western countries has been slow. One
obstacle in the west is the low number of suitable ESD cases in the upper gastrointestinal
tract, which constitutes the base for training ESD in Asia [30]
[31]. Although recent studies suggest that prior gastric ESD is not necessary for learning
colorectal ESD [23]
[32], problems with limited access of endoscopists proficient in ESD hamper widespread
implementation of ESD in western countries. Herein, we present the outcome, complications
and learning curve on the largest material of colorectal ESD in a specialized western
center.
The main purpose of ESD is to remove complex and large neoplasms en bloc to reduce
recurrences, provide adequate oncological staging and avoid unnecessary surgery [6]. One recent literature study showed that 1 out of 17 patients undergoing colorectal
ESD avoid unnecessary surgery due to superficial invasive cancer [33]. When scrutinizing 29 ESD cases harboring submucosal invasive CRC, published by
us previously, we found that 11 out of 12 potentially curable lesions were curative
resections. Under ESGE definition [10], the remaining 17 cases were primarily non-curative due to deep submucosal invasion
and in these cases ESD served as a staging procedure [10]
[24]. Moreover, in the current study, we found that in 301 patients undergoing colorectal
ESD, en bloc and R0 resection rates were 80 % and 69 %, respectively. Interestingly,
these results are similar to the outcome of resecting malignant colorectal lesions
by use of ESD (en bloc 83 %, R0 69 %) [24]. Furthermore, this outcome in efficacy is also in line with previous larger series
of colorectal ESD in western countries with an en bloc and R0 resection rate ranging
between 79 % and 88 % and 63 % and79 %, respectively [8]
[9]
[22]
[23].It is interesting to note that in the last period of this study, we observed an
en bloc rate of 98 % and R0 resection rate of 80 %, which is compatible with the best
centers in Japan [6]
[11]
[32]. In this context, it is important to note that en bloc and R0 resection rates were
significantly higher in the distal colon and rectum compared to the proximal colon,
which is in line with previous reports on colorectal ESD [9]
[23]
[34]
[35], suggesting that ESD in the right colon is far more difficult and associated with
longer learning curves compared to ESD in the distal colon and rectum. However, data
in the present study and more recently published studies from Europe indicate that
ESD in the right colon can safely be implemented although lesions larger than 5 cm
in the right colon is still a challenge for endoscopists proficient in ESD [23]. Moreover, we found that lesion size and Paris type IIa negatively influenced en
bloc and R0 resection rate in this study. Thus, localization, size and type of lesions
are important factors to consider in programs implementing colorectal ESD.
The question of what is required for an endoscopist to reach proficiency in performing
colorectal
ESD remains controversial. One arbitrary definition of efficient ESD is an R0 resection
rate of 80 % [30]
[36]. In this study, we found a R0 resection rate of 76 % in period 3 after 120 cases
of colorectal ESD. However, this measurement is prone to bias and insecure because
it depends on the percentage of colonic versus rectal ESD cases, the size and type
of lesions, which influences the efficacy of ESD as shown herein. The increase in
size observed in this study (lesion area increased by 224 % between the first and
last period) will underestimate the skill development during the learning curve of
ESD. Perhaps proficiency, defined as dissection speed, better reflects progress in
ESD. Oyama et al. suggested that a dissection speed of 9 cm2/h indicates adequate proficiency in colorectal ESD [36]. In the current study, dissection speed increased steeply to 9.6 cm2/h after 120 ESD cases and remained above that level to the end of the study, suggesting
that adequate proficiency can be reached after 120 cases of colorectal ESD. Notably,
this development is also reflected by a gradual increase in en bloc and R0 resection
rate throughout the five periods, which tested significant using linear by linear
association. It is also interesting to note that differences in en bloc and R0 resection
rates that were observed between rectal, distal colonic and proximal colonic lesions
for the entire period were diminished and non-significant during the last period after
240 ESD procedures, indicating that ESD in the proximal colon should first be attempted
when sufficient training and experience with rectal and then distal colonic lesions
have been acquired.
Complications such as perforation and bleeding are feared in ESD and one early quality
goal in
implementation of ESD is to limit the complication rate to less than 10 % [36]. In the current study, we observed 17 perforations and seven cases of bleeding,
corresponding to a total complication rate of 8 % and comparable to previous studies
from established centers in Japan [6]
[30]
[37]. It is interesting to note that we found a higher complication rate (13 %) when
investigating malignant colorectal lesions resected by using ESD, indicating an increased
degree of difficulty when resecting lesions with submucosal invasion [24]. Moreover, there was no sign of reduction in complications in the current study
between the different periods which is most likely related to the concomitant increase
in lesion size knowing that size of the lesion is an important determinant for risk
of ESD complications [6]
[35]. The great majority of the complications (75 %) were managed conservatively but
six patients required emergency surgery. It is notable that all cases requiring surgery
were located in the proximal colon, underlining the difficulty of performing ESD in
the right colon. Indeed, the overall complication rate was significantly higher in
the proximal colon compared to the distal colon and rectum in our study, which is
in line with previous studies [32]
[34]
[38]
[39].
The necessity of hospitalization of colorectal ESD patients is not scientifically
proven and
unnecessary hospitalization causes increased health care costs. Herein, we observed
that the rate of hospitalization decreased from 66 % in the first period down to 23 %
in the last period without any increase in complication rate or need for surgery,
suggesting that a great majority of ESD procedures can be safely performed as day
surgery without hospitalization, given careful patient selection and information.
This notion is in line with a recent study showing that 156 out of 171 (91 %) colorectal
ESD cases could safely and effectively be conducted on an out-patient basis [40]. These findings have significant economic impact by reducing costs associated with
colorectal ESD. However, taking the increased risk of complications when resecting
proximal lesions in the colon using ESD into account, it might be suggested that these
patients should be admitted as inpatients. One reason for implementing ESD is to reduce
the number of recurrences by avoiding piecemeal resection of large lesions [10]
[41]
[42]. Interestingly, we found seven recurrences in the 204 patients (3 %) that were followed
up endoscopically with a median follow-up time of 13 months. Notably, this recurrence
rate after ESD is in line with a large recent report from Japan showing 15 recurrences
after 390 ESD resections (4 %) [7]. Interestingly, two recurrences occurred after en bloc R0 resections, which might
be explained by cells released during the procedure that settle in the ESD wound or
by incorrect microscopic evaluation. Moreover, one patient required endoscopic dilation
of a stricture in the rectum after removal of a lesion covering more than 90 % of
circumference. Although risk of developing post-ESD stenosis in upper gastrointestinal
lesions is significant [43]
[44]
[45], risk of stricture is negligible in ESD procedures involving less than 90 % of the
circumference in the rectum [46]
[47]
[48].
There are certain limitations to our current study. All ESD procedures were exclusively
performed by one operator at one specialized single center and it is not known whether
such experiences can be directly extrapolated to other institutions. On the other
hand, inclusion of a single operator might be an advantage when studying learning
curves by circumventing performance variations between different endoscopists. Another
limitation is that 16 % of all patients undergoing ESD were not followed up endoscopically
for different reasons and the relatively short follow-up time of 13 months impairs
conclusions on long-term outcome. In addition, the retrospective nature of the study
and lack of randomization against alternative methods, such as piecemeal EMR, limits
conclusions about the exact role of ESD in overall management of large and complex
colorectal lesions although this was not a primary goal of the current study.
Conclusion
In conclusion, our data constitute the largest report on colorectal ESD in a western
setting and show that the learning curve is steep and ESD can be implemented in western
countries at tertiary expert centers, with results comparable to centers in Japan.
However, this study also underlines the importance of adequate patient selection to
ensure safe implementation of colorectal ESD since larger and proximal lesions were
associated with higher risk of complications.
Carl-Fredrik Rönnow, Noriya Uedo, Ervin Toth et al. Endoscopic submucosal dissection
of 301 large colorectal neoplasias: outcome and learning curve from a specialized
center in Europe Endoscopy International Open 2018; 06: E1340 – E1348. DOI: 10.1055/a-0733-3668
In the above mentioned article table 3 was corrected.
