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Contents lists available at ScienceDirect
Digestive and Liver Disease
journal homepage: www.elsevier.com/locate/dld
Digestive Endoscopy
Endoscopic submucosal dissection: Italian national survey on current
practices, training and outcomes
Roberta Maselli a,∗ , Federico Iacopini b , Francesco Azzolini c , Lucio Petruzziello d ,
Mauro Manno e , Luca De Luca f , Paolo Cecinato g , Giancarla Fiori h , Teresa Staiano i ,
Erik Rosa Rizzotto j , Stefano Angeletti k , Angelo Caruso l , Franco Coppola m ,
Gianluca Andrisani n , Edi Viale c , Guido Missale o , Alba Panarese p , Alessandro Mazzocchi q ,
Paola Cesaro r , Mariachiara Campanale d , Pietro Occhipinti s , Ottaviano Tarantino t ,
Cristiano Crosta h , Piero Brosolo u , Sandro Sferrazza v , Emanuele Rondonotti w ,
Arnaldo Amato w , Lorenzo Fuccio x , Guido Costamagna y,z,A , Alessandro Repici a,B
a
Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Humanitas University, Milan, Italy
Gastroenterology Endoscopy Unit, S. Giuseppe Hospital, Rome, Italy
c
Division of Gastroenterology & G.I. Endoscopy, Vita Salute San Raffaele University, Milan, Italy
d
Digestive Endoscopy Unit, Division of Gastroenterology Fondazione A. Gemelli–Università Cattolica del Sacro Cuore Hospital, IRCCS, Rome, Italy
e
Digestive Endoscopy Unit, USL Modena, Carpi Hospital, Italy
f
Division of Gastroenterology & G.I. Endoscopy, Ospedali Riuniti Marche Nord Hospital, Pesaro, Italy
g
Unit of Gastroenterology and Digestive Endoscopy, USL-IRCCS Reggio Emilia Hospital, Reggio Emilia,Italy
h
IEO, Digestive Endoscopy Unit, Istituto Europeo di Oncologia IRCCS Hospital, Milano, Italy
i
Digestive Endoscopy Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, TO, Italy
j
Division of Gastroenterology & G.I. Endoscopy, S. Antonio Hospital, Padova, Italy
k
Digestive Endoscopy Unit, Sant’Andrea Hospital, a Sapienza university, Roma, Italy
l
Division of Gastroenterology & G.I. Endoscopy, Baggiovara Hospital, AOU di Modena, Italy
m
Digestive Endoscopy Unit, Division of Gastroenterology, ASLTO4, Turin, Italy
n
Digestive Endoscopy Unit, Campus Biomedico Hospital, Rome, Italy
o
Digestive Endoscopy Unit, ASST Spedali Civili, Brescia University, Italy
p
Department of Gastroenterology and Digestive Endoscopy, National Research Institute specialized in Gastroenterology " S. De Bellis" , Castellana Grotte,
BA, Italy
q
Gastroenterology Endoscopy Unit, San Giovanni Battista Hospital, San Giovanni battista, Italy
r
Endoscopy Unit, Fondazione Poliambulanza, Brescia, Italy
s
Division of Gastroenterology, " Maggiore della Carità " Hospital and University, Novara, Italy
t
Division of Gastroenterology & G.I. Endoscopy, San Giuseppe Hospital, ASL Toscana centro, Empoli, Italy
u
Division of Gastroenterology, Hospital of Pordenone, Pordenone, Italy
v
Gastroenterology and Endoscopy Unit, Santa Chiara Hospital, APSS, Trento, Italy
w
Gastroenterology and Digestive Endoscopy Unit, Valduce Hospital, Como, Italy
x
Department of Medical and Surgical Sciences, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
y
Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
z
Cattolica del Sacro CuoreUniversity, Centre for Endoscopic Research Therapeutics and Training CERTT, Roma, Italy
A
Université de Strasbourg Institut d’Etudes Avancées USIAS, Strasbourg, France
B
Humanitas University, Department of Biomedical Science, Milan, Italy
b
a r t i c l e
i n f o
Article history:
Received 29 December 2018
Accepted 11 September 2019
Available online xxx
Keywords:
Early GI tumor
a b s t r a c t
Background and Aims: Most of the evidence supporting endoscopic submucosal dissection (ESD) comes
from Asia. European data are primarily reported by specialized referral centers and thus may not be
representative of common European ESD practice. The aim of this study is to understand the current
state of ESD practice across Italian endoscopy centers.
Methods: All Italian endoscopists who were known to perform ESD were invited to complete a structured
questionnaire including: operator features and competencies, ESD training details and clinical outcomes
over a 2-year period.
∗ Corresponding author at: Digestive Endoscopy Unit, Humanitas Research Hospital, Via Manzoni 56, Rozzano Milano, 20089, Italy.
E-mail address: roberta.maselli@humanitas.it (R. Maselli).
https://doi.org/10.1016/j.dld.2019.09.009
1590-8658/© 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
and outcomes. Dig Liver Dis (2019), https://doi.org/10.1016/j.dld.2019.09.009
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Endoscopy
ESD
Survey
Results: Twenty-nine operators from 23 centers (69% response rate) completed the questionnaire: 18 (62%)
were <50 years old; 7 (24%) were female; 16 (70%) were located in Northern Italy. Overall ESD volume was
<40 cases in 9 (31%) operators, 40–80 in 8 (27.5%), 80–150 in 4 (13.8%) and >150 in 8 (27.5%). Colorectal
ESD was predominant for operators with an experience >80 cases. En-bloc resection rates ranged from
77.2 to 97.2% depending on the anatomic location with an R0 resection rate range of 75.3–93.6%. ESD
perforation rates in the colon and rectum were significantly lower when experience was >150 compared
to 80–150 cases (p < 0.0001 and p = 0.006 for colon and rectum, respectively).
Conclusion: ESD in Italy is performed by a significant number of operators. Overall, Italian endoscopists
performing ESD have achieved a good competence level. However, there is much variability in training
protocols, initial supervision of procedures, practice settings, case mix and procedural volume/year that
are likely responsible for some of the suboptimal resectional outcomes and increased perforation risk,
mainly in the colon. Standardized training programs, practice parameters and auditing of outcomes are
required.
© 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Background
Endoscopic submucosal dissection(ESD) was developed to
bypass the limits of endoscopic mucosal resection (EMR), facilitating en-bloc resection of GI (gastrointestinal) lesions >20 mm.
En-bloc resection potentially leads to an oncologically adequate
resection with a low risk of local recurrence. ESD was first described
by Japanese endoscopists in 2008; only now is it progressively gaining more attention in Western countries.
Depite its widespread adoption across Asian countries, in
Europe ESD is still considered a difficult and risky procedure. Until
now, only a few European centers have been able to achieve outcomes at the level reported by Japanese experts.
The main difficulty in performing ESD is its long learning
curve: this complex and delicate procedure involves many aspects,
namely (1) lesion recognition and characterization; (2) accurate
decision making to apply to correct treatment to the lesion at hand
(mucosal resection vs. ESD vs. surgical resection); (3) understanding of patient positioning and use of gravity to provide traction;
(4) many technical aspects including a deep understanding of the
proper use of the electrosurgical unit, various instruments and
devices; and (5) a high level of endoscopic skill and refined tip control so as to be able to safely complete the procedure and manage
complications [1]. To our knowledge, a structured learning setting is still not available in Italy, as in many European countries,
thus most of the current Italian ESD performers have been trained
abroad, mainly in Japan, across different settings and periods of
time.
Due to these varying degrees of training and also to
the different practice settings across the country (academic/community/tertiary), it is desirable to survey the Italian ESD
experience in order to audit ESD performance as a prerequisite to
the optimization of future training, practice parameters and patient
outcomes. The aim of this study, therefore, was to gain a greater
understanding of ESD adoption, training of physicians, volume of
procedures and practice parameters (including intra-procedural,
post-procedural, and follow-up outcomes) across Italian centers
who routinely perform advanced tissue resection.
2. Materials and methods
Between March and April 2018, Italian endoscopists who were
known to perform GI (gastrointestinal) advanced tissue resection
(identified through peer networks, conference participation and
published works) were invited by email to complete a structured
questionnaire comprising operator features and endoscopic competencies, details of ESD training and retrospective extraction of
ESD outcomes for esophageal, gastric and colorectal neoplasms
over a 2-year period from January 2016 to December 2017.
For the purpose of collecting detailed clinical information about
ESD practice, participants were asked to retrospectively self-report
outcomes for all consecutive GI tract lesions resected by ESD technique (inclusion criterion) excluding those resections intentionally
performed from the beginning via hybrid techniques (exclusion criteria): specifically endoscopic mucosal resection (EMR) after small
mucosal incisions, EMR after a circumferential mucosal incision, or
EMR after partial submucosal dissection.
Resectional outcomes were defined as follows:
- Complete resection = absence of any endoscopically visualized
residual neoplasia at the end of the procedure.
- ESD = complete resection performed with an electrosurgical knife
without the use of a snare or other such accessory instrument
(“pure” ESD).
- Hybrid-ESD = complete resection initially planned to be performed entirely by ESD but converted to EMR for any reason.
- R0 = histopathological complete resection with negative vertical
and lateral margins (applied only to en-bloc resections).
- Curative resections = depending on the organ, according to the
ESGE criteria [2].
To evaluate the safety of the ESD procedures, we also
assessed the self-reported rate of serious adverse events during and after the procedure, namely intra-procedural bleeding
(defined as bleeding sufficient to require ESD interruption), postprocedural bleeding (defined as any post-ESD hematochezia or a
decrease in hemoglobin concentration of more than 2 g/dl requiring transfusion, endoscopic hemostasis, hospital re-admission or
surgical/radiological interventons), intra- and post-procedural perforations and the details of subsequent management.
3. Statistics
Data were collected, analysed and extracted with graphs and
analysis performed using SPSS (IBM SPSS Inc, Chicago, Illinois).
Percentages were calculated based on the total number of survey participants and the number of responses to each individual
question. Data were collected and analysed by means of descriptive statistics (mean and standard deviation). The Student’s t test
was used to compare the distribution of continuous variables by
outcome. All differences were considered significant at two-sided
P-value <0.05.
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
and outcomes. Dig Liver Dis (2019), https://doi.org/10.1016/j.dld.2019.09.009
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4. Results
Forty-two operators from 34 Italian centers were invited by
e-mail to participate in the survey and 29 individuals (69%)
from 23 centers completed the questionnaire. Data were analyzed
according to four categories: (1) operator demographics and competencies; (2) ESD training and initial experience; (3) ESD practice
settings; (4) ESD outcomes. Information was provided from 15
(65.3%) centers in Nothern Italy, 7 (30.5%) from the Center and 1
(4.2%) from the South. No centers were represented from the islands
of Sicily or Sardinia (Fig. 1).
Four centers (17.3%) had two ESD operators, only 1 (4.4%) had
three; all the other centers had a single operator (78.3%) performing ESD. Of the participating centers, 7 (30.5%) were an academic
hospital and 16 (69.5%) were community hospitals; in 3 (13%)
the endoscopic unit was part of a Surgical Department and in 20
(87%) part of a Gastroenterological Department. Most of the centers
(19/23, 82.6%) had an Emergency Department.
5. Demographics and competencies
Data on the 29 phsyicians were analyzed; most (75.9%) were
male (M/F = 22/7). Eleven (37.9%) were >50 years old, 10 (34.5%)
41–50 years old and 8 (27.6%) 30–40 years old; none were younger
than 30 years old. The date of medical degree completion ranged
from 1975 to 2010.
Most of the operators (75.9% 22/29) were specialized in
gastroenterology, 4 (13.8%) in surgery and 3 (10.3%) in both gastroenterology and surgery.
Regarding endoscopic competencies, all declared to routinely
perform EMR, 25/29 (86.2%) were also competent in ERCP, 11/29
(37.9%) in EUS, 14/29 (48.3%) in endoscopic suturing and 6
(20.7%) in per-oral endoscopic myotomy (POEM). Finally, almost
all operators (28/29, 96.6%) routinely performed endoscopy for GI
emergencies.
6. ESD training and initial experience
Ranging from 2002 to 2017, 25/29 (86.2%) of the endoscopists
interviewed had specific traning for ESD: 9 of them (31%) for a single period of time and 16 (55.2%) for more than 1 period. The total
training period was <3 weeks for 12 participants (41.4%), 1 to 3
months for 8 (27.6%) and more than 3 months for 5 (17.2%). Thirteen endoscopists (44.8%) were trained in Japan, 6 (20.7%) in Europe
outside of Italy, and 6 (20.7%) in Italy.
All but 2 (6.9%) respondents started their initial ESD experience
on ex-vivo models: 8 (27.5%) performed ESD on ≤5 models, 11
(11/29, 37.9%) on 6–10 models, 4 (4/29, 13.8%) on 11–25 models, 4
(4/29, 13.8%) on >26 models. The mean number of ex-vivo models
used in this training phase was 11.57 ± 11.6.
After the initial ex-vivo experience, all but 7 (24.1%) performed
in-vivo animal ESD procedures: 14 of them (48.3%) in ≤5 models,
5 (17.2%) in 6–10 models and 3 (10.3%) in >10 models. The mean
number of in-vivo models used in this training phase was 5.04 ± 5.8.
Analyzing the first 40 cases performed in humans, ESD was
mainly performed in the stomach and in the rectum, whereas few
operators treated esophageal/GEJ (gastro-esophageal junction) and
colonic lesions (Fig. 2).
For most of the participants (19/29, 65.5%), the first few patients
were treated without any expert supervision; a tutor was present
in 1–5 procedures in 7/29 (24.1%) and in more than 5 procedures
in 3/29 (10.3%).
All participants were asked to estimate their overall GI ESD
experience according to different anatomic locations and to seven
different range frequencies (0, <10, 11–20, 21–40, 41–80, 81–150,
3
>150). Considering a total volume <40 procedures performed as
a low ESD experience indicator [3], data demostrated that almost
1/3 of the participants were in their initial experience phase (9/29,
31%). These data are shown in Fig. 3.
7. ESD settings
Most of the participants (23/29, 79.3%) reported inpatient hospitalization of all patients after the ESD procedure; only 6 (20.7%)
also used a day-surgery setting at times. Almost half of the participants used deep unconscious sedation administered by a dedicated
anesthesiologist for both upper and lower GI ESD (44.8% for upper
GI and 48.2% for lower GI).
Only 4/29 respondents (13.8%) routinely performed an ECG,
blood tests and/or a chest X-ray before all ESDs; 22/29 (75.9%) only
performed them due to institutional anesthesiology policy requirements; 3/29 (10.3%) did not perform any routine pre-operative
tests.
Regarding endoscopic technique for ESD, all reported using an
HD-endoscope with virtual/digital chromoendoscopy, the exact
modality being dependent on the endoscope brand available in
their center.
As to the further characterization of GI lesions, different staining
solutions were reported; dye solutions for conventional chromoendoscopy were routinely sprayed before resections by 13/29 (44.8%)
participants, while only occasional use of conventional chromoendoscopy was reported by 16/29 (55.2%).
Before resection, a radiological (CT or MRI depending by the
organ) and/or EUS staging modality was routinely performed by
13/29 (44.8%) for upper-GI lesions and by 10/29 (34.5%) for lower
GI lesions; 2/29 (6.9%) were using these modalities only in selected
cases.
The usage of ESD operating devices/accessories was variable: a
CO2 insufflator was used and available for most of the operators
(26/29, 89.7%); almost all (28/29, 96.6%) used a an endoscope with
forward water-jet capability. Most of the participants (58.6%) preferred a straight distal attachment cap and 27/29 (93%) used either
a Dualknife (Olympus, Japan) or a HybridKnife (ERBE, Germany)
for the mucosal incision and subsequent submucosal dissection.
In particular, 9/27 (33.3%) preferred a Dualknife, 6/27 (22.3%) preferred the HybridJnife and 11/27 (40.7%) used both knifes at times.
A water-jet knife (ERBE Hybridknife, Olympus J-knives or Fujifilm
flush-knife) was available in the endoscopic unit for 23/29 (79.3%)
participants, and it was preferentially used by 17/29 (58.6%). The
use of different knives during a single ESD procedure was reported
to be very common (in >30% of the procedures) by 5 participants
(17.2%), common (in 10–30% of the procedures) by 3 (10.3%) and
uncommon (in <10% of the procedures) by 21 (72.4%).
Most of the endoscopists interviewed (19/29, 65.5%) preferred
saline +/- an additional solution (glycerol, hyaluronic acid, hydroxypropylmethylcellulose, plasma expander) to be injected in the
submucosa; 6/29 (20.7%) and 4/29 (13.8%) preferred pure glycerol
solution and plasma expanders, respectively. Finally, 26/29 (89.7%)
added dilute epinephrine to the injectate.
8. ESD outcomes
Outcomes data were collected for a two year period (Jan.
201–Dec. 2017) and included en-bloc resection rate, R0 resection
rate, curative resection rate and complications. Esophageal/GEJ,
gastric, colonic and rectal ESDs were separately analyzed.
Overall, the data showed a high en-bloc rate, with a peak rate
for esophageal ESD (95%), and a lower rate for colonic ESD (77%).
A similar trend was observed for the R0 resection rate (88% for
esophageal, 75% for colonic ESD). The curative resection rate was
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
and outcomes. Dig Liver Dis (2019), https://doi.org/10.1016/j.dld.2019.09.009
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Fig. 1. Geographical distribution of the 23 centers that completed the ESD survey.
Table 1
ESD outcomes related to 2016 and 2017, separately reported for esophageal/GEJ, gastric, colonic and rectal ESDs.
Esophagus/GEJ
N
Age, mean (±SD)
Female sex, n (%)
Total en-bloc, n (%)
ESD en-bloc
Hybrid ESD en-bloc
Piecemeal complete resection
Incomplete resection
Total R0, n (%)
ESD R0
Hybrid ESD R0
Total Curative resection, n (%)
ESD curative resection, n (%)a
Piecemeal curative resection, n (%)a
Stomach
Colon
Rectum
2016
2017
2016
2017
2016
2017
2016
2017
60
63.8 ± 11.6
25 (41.6)
57 (95)
53
4
3
–
53 (88.3)
49
4
48 (80)
48 (84.2)
–
49
62.7 ± 8.8
9 (18.4)
47 (95.9)
44
3
1
1
43 (87.7)
40
3
38 (77.5)
37 (78.7)
1 (100)
251
79.8 ± 30.9
59 (23.5)
240 (95.6)
219
22
8
2
235 (93.6)
216
19
211 (84)
209 (86.7)
2 (25)
251
55.8 ± 29.3
88 (35)
244 (97.2)
205
40
5
1
228 (90.8)
197
31
206 (82)
201 (82.0)
5 (100)
316
80 ± 33.4
97 (30.7)
244 (77.2)
181
63
67
5
239 (75.6)
174
65
236 (74.6)
179 (73.3)
57 (85.0)
293
42.3 ± 34
91 (31)
241 (82.2)
188
53
46
6
226 (77.1)
175
51
214 (73)
182 (75.5)
32 (69.6)
383
68.9 ± 5
123 (32.1)
331 (86.4)
262
69
47
5
314 (81.9)
252
62
276 (72)
236 (71.3)
40 (85.1)
353
68.7 ± 4.2
103 (29.2)
292 (82.7)
232
60
59
2
266 (75.3)
211
55
241 (68.2)
201 (68.8)
40 (67.8)
a
The percentage refers to the relative curative resection rates for ESD and for piecemeal resection (number of curative resections obtained by ESD and piecemeal resection,
compared to the total number of ESD and piecemeal resections, respectively).
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
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Fig. 2. Reported anatomic location and number of lesions treated at the beginning of human ESD experience (first 40 patients).
highest for gastric and esophageal lesions (84% and 80%, respectively) and lowest for rectal lesions (68%). At all anatomic locations,
the curative resection rate was similar for en-bloc resections
compared to piecemeal complete resections, although a smaller
number of piecemeal resections have been performed compared
to ESD. These data are summarized in Table 1.
Analyzing the safety outcomes (Table 2), colonic ESD was
associated with a higher risk of complications (intra-procedural
perforation rate of 8.5% in 2016 and 7.1% in 2017). Overall, postprocedural perforations were rare, with the frequency ranging from
0.3-0.8% across the anatomic locations. In total, eight out of 130
(6.1%) perforations (intra- or post-procedural) required surgery.
Intra-procedural bleeding caused the interruption of the ESD
procedure in 0.3–1.0% of cases. On the contrary, significant postprocedural bleeding occurred more commonly, especially in the
stomach (10.7% in 2016 and 7.9% in 2017). Regardless of the site of
ESD, in most of the cases (55.6–100%), endoscopic intervention led
to successful control of the bleeding episode; few cases required
surgery and/or radiological interventions (5.0–8.7%).
Death within 30-days of the ESD procedure was reported after 1
gastric ESD (0.4%) and 1 rectal ESD (0.3%). The patient who underwent the gastric ESD was a 78 year-old man with a history of remote
myocardial infarctions. His chronic anti-platelet agent had been
held for 5 days prior to the procedure. Forty-eight hours after an
uneventful ESD procedure he suffered a cardiac arrest (the day he
was to resume his antiplatelet agent) and died 3 days later. The
second fatal event was in a 76 year-old woman who underwent a
rectal ESD complicated by a small intraprocedural perforation that
was successfully clipped. She died 4 days after the procedure most
likely due to a pulmonary embolism.
Considering the expertise of the operators, en-bloc ESD rates in
the esophagus were higher when experience was ≥40 cases com-
pared to <40 cases (p = 0.002). ESD perforation rates in the colon
and rectum were significantly lower when experience was >150
cases as opposed to 80–150 cases (p = 0.0001 and 0.006, for colon
and rectum, respectively) although no different when compared to
operators with experience range of 40–80 cases (p = 0.7 and 1.0, for
colon and rectum, respectively).
In particular in colon and rectum ESDs, perforation rate was
higher in much experienced operator (80–150 ESDs) compared to
those with less experience (40–80 ESDs) (30 vs 6% p = 0.0001 for
colon and 18 vs 4% p = 0.002 for rectum). The outcomes according
to operator experience are summarized in Table 3.
9. Discussion
ESD is a precise and complex oncological procedure that
requires a dedicated training program to acquire an adequate
skillset even for physicians with proven expertise in other areas
of therapeutic endoscopy. Moreover, the procedure is time consuming and both cognitively and technically demanding. In 2008,
a panel of Asian and non-Asian experts proposed a “step-up
approach” to establish an ESD program; their recommendations
comprised a minimum case load per year (10–20 ESDs per year)
and the creation of a prospective registry [1].
Due to the lack of data regarding ESD practices and outcomes in
our country, we felt it was appropriate to construct an updated picture of real-world ESD practice in Italy. The idea of the survey and
its structure was generated during an ESD meeting in Milan, when
after a fruitful discussion it was realized that ESD was more commonly performed than expected. This raised the need to ascertain
more details on the type of training completed, practice settings
and quality metrics for ESD procedures being perfomed in Italy.
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
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Fig. 3. Estimated overall ESD volume/operator according to different anatomic locations.
Table 2
Safety outcomes related to the years 2016 and 2017, reported separately for esophageal/GEJ, gastric, colonic and rectal ESDs.
N
Total Intrap. Perf., n. (%)
Intrapr. perf, conservative treatment
Intrapr. perf, surgery
Total Postp. Perf., n. (%)
Postpr. perf, conservative treatment
Postpr. perf, surgery
Intrapr. bleeding, ESD interruption, n. (%)
Total postpr. Bleeding, n. (%)
Postpr. bleeding, endoscopic emostasis,
Postpr. bleeding, surgery/rad
Postpr. bleeding, transfusion
30-day mortality, n. (%)
Esophagus/GEJ
Stomach
2016
2017
2016
2017
2016
2017
2016
2017
60
1 (1.6)
1 (100)
–
–
–
–
–
1 (1.7)
1 (100)
–
–
–
49
1 (2)
1 (100)
–
–
–
–
–
–
–
–
–
–
251
14 (5.6)
12 (85.7)
2 (14.3)
–
–
–
–
27 (10.7)
15 (55.6)
2 (7.4)
10 (37)
1 (0.4)
251
17 (6.8)
16 (94.1)
1 (5.9)
1 (0.4)
–
1
1 (0.4)
20 (7.9)
12 (60)
1 (5)
7 (35)
316
27 (8.5)
26 (96.3)
1 (3.7)
2 (0.6)
1
1
1 (0.3)
9 (2.8)
5 (55.6)
–
4 (44.4)
–
293
21 (7.1)
21 (100)
–
1 (0.3)
–
1
1 (0.3)
12 (4)
7 (58.3)
1 (8.4)
4 (33.3)
–
383
28 (7.3)
27 (96.4)
1 (3.6)
3 (0.8)
3
–
4 (1)
23 (6)
13 (56.5)
2 (8.7)
8 (34.8)
1 (0.3)
353
12 (3.4)
12 (100)
–
2 (0.5)
2
–
1 (0.3)
24 (6.8)
17 (70.8)
–
7 (29.2)
–
As the experts have declared, “Quality control for ESD should
provide some guarantee that the right endoscopists are doing the
appropriate procedures for their level of expertise” [1]. Due to the
high level of skill required (in doing the procedure itself and managing its complications), ESD should only be attempted by expert
endoscopists. In line with this statement, all operators who participated in this survey declared to routinely perform EMR; almost all
(96.6%) routinely performed endoscopic emergencies; 86.2% were
also competent in ERCP.
During the initial ESD experience, as Japanese experts have
suggested, one should be aware that lesions located in the distal stomach and rectum may be easier and safer to treat; once
expertise is gained in these locations, one could move to more difficult locations (namely the proximal stomach and then finally the
Colon
Rectum
colon and esophagus) [4]. Several studies report the achievement
of en-bloc resection in >80% and a complication rate of <10% as the
competence level to be achieved in the early learning phase [3–5].
Moreover, the suggested cut-off for this competence level assessment is after 30 tutored gastric procedures [6,7] and 40 tutored
colorectal procedures [8,9].
From this point of view, we must recognize a lack of mastermentors and structured training programs in Western countries.
For most of the participants in our survey (65.5%), the first patients
were treated without any supervision. Only for 3/29 (10.3%) endoscopists was a tutor was present in ≥5 procedures during the initial
human experience.
Despite this deficiency, for most of the respondents in our survey, the first 40 lesions treated in humans were appropriately
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Table 3
ESD outcomes, in terms of en-bloc resection and perforation rate, reported according to experience level. P1 statistical difference between <40 ESDs and 40–80 ESDs; P2
statistical difference between 40–80 ESDs and 80–150 ESDs; P3 statistical difference between 80–150 ESDs and >150 ESDs.
Operator experience levels
<40 ESDs
40–80 ESDs
80–150 ESDs
>150 ESDs
N (%)
P
N (%)
P3
0.002
0.68
0.02
1.0
10 (100)
77(97)
36 (90)
49 (87)
0.05
1.0
0.04
0.83
49 (94)
172 (94)
349 (78)
360 (87)
0.02
0.49
0.03
1.0
1.0
0.001
0.003
0.5
1 (10)
8 (10)
12 (30)
10 (18)
0.001
0.6
0.0001
0.002
1 (2)
11 (6)
29 (6)
22 (5)
0.03
0.4
0.0001
0.006
N (%)
N (%)
P
En bloc
Esophagus
Stomach
Colon
Rectum
4 (80)
79 (96)
22 (91)
83 (84)
40 (95)
156 (98)
76 (79)
131 (85)
Perforation
Esophagus
Stomach
Colon
Rectum
0
2 (2.4)
5 (21)
7 (7)
0
11(7)
6 (6)
6 (4)
1
performed only in the stomach (62%) and/or the rectum (58%), in
line with the training steps proposed by our Japanese colleagues.
In constrast, the overall Italian ESD series comprises more
colonic and rectal cases than upper-GI cases; even the Italian
“super-experts” (>150 cases) had a limited experience in the stomach, compared to their experience in removing colorectal lesions.
This is almost certainly due to the lower Italian incidence of dysplasia/superficial gastric cancer. Japan has 10-fold higher incidence
of gastric cancer than in most Western countries [10], leading to
programmatic gastric cancer screening and an increased opportunity to find neoplasia at an early stage. Another key aspect is
the lower capacity of Western endoscopists, compared to Eastern
endoscopists, in early upper-GI cancer detection and characterization, thus in accurate endoscopic tumor staging and finally in
making the correct therapeutic decision. Essentially we are chasing our own tail: the low number of superficial upper-GI cancers
found lessens our ability to detect and potentially treat them.
Along these lines, the cognitive aspect of lesion assessment and
decision-making as to whether ESD is the best approach for a particular lesion (as opposed to EMR or surgery) cannot be underscored
enough. Errors in judgment can lead to both over-treatment of
lesions (for example, choosing ESD for a lesion with likely only LGD
that could be more easily and more safely treated by EMR techniques) or under-treatment (for example, choosing to attempt ESD
for a lesion with clear signs of deeply invasive cancer, exposing
the patient to potential complications and an incomplete resection). Although one may be able to acquire the technical skills to
safely perform ESD in a relatively short period of time, this cognitive
aspect takes much longer to fully develop and a proper ESD training
program should be designed to be comprehensive in this key area
[2–11]. In our survey, it is difficult to judge this aspect as we were
unable to collect specific data as to the size/morphology and final
histology of all lesions. Further studies are needed to investigate
this aspect and ideally a centralized national registry would make
these details readily available.
The second ESD competence level cut-off, as previously
reported, is the achievement of an en-bloc resection rate >80% and
a complication rate <10%. In our group, this goal was achieved at all
levels of endoscopist expertise, regardless of ESD location. Considering the expertise level of the operators, particularly regarding the
perforation rate, there is a paradox in that the operators who have
performed 80–150 ESDs had a higher perforation rate compared to
those an experience of <80 ESDs; on the other hand, super-experts
(>150 ESDs) reported a lower perforation rate than experts (80–150
ESDs). This could be explained by the fact that more experienced
operators attempt more difficult ESDs with a higher inherent risk
of perforation, yet only the super experts can maintain a low complication rate.
2
World-leading centers in East Asia have reported high en-bloc
resection rates ranging from 87% to 97% but lower rates of R0 resection (75% to 91%) [12,13]. Furthermore, a 2018 meta-analysis of all
English language ESD studies (regardless of location) showed significantly higher curative (82% vs 71%), en-bloc (95% vs 85%) and
R0 rates (89% vs 85%) for Eastern versus Western countries [14].
In comparison, our data show an overall high en-bloc rate, highest
for esophageal ESD (95%) and lowest for colonic ESD (77%). This
trend was confirmed by the R0 rate (88% for esophageal, 75% for
colonic ESD). Curative resection rate was highest for gastric and
esophageal lesions (84% and 80% respectively) and lowest for rectal
lesions (68%).
A recent meta-analyis by Fuccio et al. [15] on the outcomes of
colorectal ESD, comprising Asian and non-Asian studies, reported
an 82.9% R0 resection rate for the standard ESD technique, but a
significantly lower rate in non-Asian countries (71.3% vs. 85.6%).
Compared to these results, taking together colonic and rectal ESDs,
our outcomes show an en-bloc resection rate of 82.4% and R0 rate
of 77.7%.
Regarding the second competency parameter, the complication
rate, the overall intra-procedural perforation rate was 6.2% in our
survery, in concordance with a previous national Japanese survey
reporting an incidence of 5.9% [16], both <10% as aspired. Despite
these good results, in our study 8/130 (6.1%) perforations required
surgery. One aspect to consider is that different training protocols
for the early phase of experience and lack of training in the colonic
location may be responsible for this suboptimal outcome. In the
cited meta-analysis above, surgery was required in 1.1% of ESDrelated adverse events, with a significant difference between nonAsian and Asian countries (3.1% vs 0.8%).
Overall, the achievement of the proposed cut-offs for ESD practice outcomes (although the en-bloc rate of colonic ESDs was
slightly lower than 80%) confirms, that from this survey, Italian
endoscopists have achieved a good competence level. This is particularly important considering the lack of mentors or a structured
training program as well as a lower opportunity to consolidate
training in the gastric location.
The European ESD experience has been mostly published from
single centers [17–21]. To our knowledge, only other two national
ESD surveys have been previously conducted: one from Asia on
colorectal ESD [22] and one from France [23] on all GI ESDs from
2008–2013. Our results are similar to those achieved in the French
survey in terms of en-bloc resection rate, R0 resection rate and
complications.
The strength of our study is the large number of endoscopists
involved (69% of all invitees), thus the results of our survey should
be considered reliable. This is an honest and accurate representation of current Italian ESD practice: all known ESD performers
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
and outcomes. Dig Liver Dis (2019), https://doi.org/10.1016/j.dld.2019.09.009
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were invited, regardless of experience, ranging from those who
were at the initial experience to those considered very expert. On
the other hand, the main limitations of our study are the retrospective design and reliance on self-reported experience and outcomes.
It is all possible that not all endoscopist performing ESD in Italy
were invited to participate. We also do not have data on the size,
morphology or final histology of the lesions removed to comment
on the appropriateness of ESD as the chosen treatment; this highlights the lack of a structured ESD program at most centers and
the absence of an ESD registry. This clearly needs to be changed for
the future.
In conclusion, we can affirm that ESD in Italy is performed by a
high number of operators who are not homogenously distributed
across the different regions of the country. Overall, based on this
survey, it would seem that ESD is being performed safely and above
the aspirational goals set by expert consensus opinion. However,
this real-world snapshot of Italian ESD performance reveals much
variability in training, endoscopy unit set-up and the initiation
of individual ESD practices. In particular, we must highlight the
wide variation in the quantity and quality of training and that for
most operators the first patients were treated without adequate
expert supervision. Ideally, a standardized and certifiable ESD training program for Western endoscopists should be established that
includes an absolute requirement for expert supervision of initial
human cases at the trainee’s home institution. In fact, this is one of
the advertised goals of the ESGE education committee for the near
future. As to the practice setting, CO2 insufflation was not universally available and the method of sedation was non-standardized.
Although this may be due to practice constraints at individual
worksites, and thus seemingly unavoidable, it is better to delay performing ESD until these important patient safety parameters are in
place. Finally, the absence of data on lesion characteristics and histology speaks to the lack of institutional registries to monitor ESD
appropriateness and outcomes. Ideally, a comprehensive national
ESD registry would be launched.
This study establishes the need for a structured training program, standardized service delivery and a national ESD registry, in
order to optimize ESD practice in Italy.
Conflicts of interest
None declared.
References
[1] Deprez PH, Bergman JJ, Meisner S, Ponchon T, Repici A, Dinis-Ribeiro M, et al.
Current practice with endoscopic submucosal dissection in Europe: position
statement from a panel of experts. Endoscopy 2010;42:853–8.
[2] Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A,
et al. Endoscopic submucosal dissection: european society of gastrointestinal
endoscopy (ESGE) guideline. Endoscopy 2015;47:829–54.
[3] Oyama T, Yahagi N, Ponchon T, Kiesslicch T, Berr F. How to establish endoscopic submucosal dissection in western countries. World J Gastroenterol
2015;21(40):11209–20.
[4] Ono H, Kondo H, Gotoda T, Shirao K, Yamaguchi H, Saito D, et al. Endoscopic
mucosal resection for treatment of early gastric cancer. Gut 2001;48:225–9.
[5] Gotoda T, Friedland S, Hamanaka H, Soetikno R. A learning curve for advanced
endoscopic resection. Gastrointest Endosc 2005;62:866–7.
[6] Kukushima N, Fujishiro M, Kodashima F, Muraki Y, Tateishi A, Omata M. A learning curve for endoscopic submucosal dissection of gastric epithelial neoplasms.
Endoscopy 2006;38:991–5.
[7] Yamamoto S, Uedo N, Ishihara R, Kajimoto N, Ogiyama H, Fukushima Y,
et al. Endoscopic submucosal dissection for early gastric cancer performed by
supervised residents: assessment of feasibility and learning curve. Endoscopy
2009;41:923–8, 514.
[8] Hotta K, Oyama T, Shirohara T, Miyata Y, Takahashi A, Kitamura Y, et al. Learning curve for endoscopic submucosal dissection of large colorectal tumors. Dig
Endosc 2010;22:302–6.
[9] Sakamoto T, Saito Y, Fukunaga S, Nakajima T, Matsuda T. Learning curve
associated with colorectal endoscopic submucosal dissection for endoscopists experienced in gastric endoscopic dissection. Dis Colon Rectum
2011;54:1307–12.
[10] Draganov PV, Coman RM, Gotoda T. Training for complex endoscopic procedures: how to incorporate endoscopic submucosal dissection skills in the West?
Expert Rev Gastroenterol Hepatol 2014;8:119–21.
[11] Friedel D, Stavropoulos SN. Introduction of endoscopic submucosal dissection
in the West. World J Gastrointest Endosc 2018;10:225–38.
[12] Bourke MJ, Neuhaus H. Colorectal endoscopic submucosal dissection: when
and by whom? Endoscopy 2014;46:677–9.
[13] Heitman SJ, Bourke MJ. Endoscopic submucosal dissection and EMR for large
colorectal polyps: “the perfect is the enemy of good”. Gastrointest Endosc
2017;86:87–9.
[14] Daoud DC, Suter N, Durand M, Bouin M, Faulques B, von Renteln D. Comparing
outcomes for endoscopic submucosal dissection between Eastern and Western countries: a systematic review and meta-analysis. World J Gastroenterol
2018;24:2518–36.
[15] Fuccio L, Hassan C, Ponchon T, Mandolesi D, Farioli A, Cucchetti A, et al. Clinical
outcomes after endoscopic submucosal dissection for colorectal neoplasia: a
systematic review and meta-analysis. Gastrointest Endosc 2017;86:74–86.
[16] Tsuda S. Complications related to endoscopic submucosal dissection (ESD) of
colon and rectum and risk management procedures. Early colorectal. Cancer
2006;10:539–50.
[17] Neuhaus H. Endoscopic submucosal dissection in the upper gastrointestinal
tract: present and future view of Europe. Dig Endosc 2009;21(Suppl. 1):S4–6.
[18] Probst A, Golger D, Arnholdt H, Messmann H. Endoscopic submucosal dissection of early cancers, flat adenomas, and submucosal tumors in the
gastrointestinal tract. Clin Gastroenterol Hepatol 2009;7:149–55.
[19] Bialek A, Pertkiewicz J, KarpinÅL ska K, Marlicz W, Bielicki D, Starzynska T.
Treatment of large colorectal neoplasms by endoscopic submucosal dissection:
a European single-center study. Eur J Gastroenterol Hepatol 2014;26:607–15.
[20] Probst A, Golger D, Anthuber M, Markl B, Messmann H. Endoscopic submucosal dissection in large sessile lesions of the rectosigmoid: learning curve in a
European center. Endoscopy 2012;44:660–7.
[21] Schumacher B, Charton JP, Nordmann T, Vieth M, Enderle M, Neuhaus H.
Endoscopic submucosal dissection of early gastric neoplasia with a water
jet-assisted knife: a Western, single-center experience. Gastrointest Endosc
2012;75:1166–74.
[22] Boda K, Oka S, Tanaka S, Nagata S, Kunihiro M, Kuwai T, et al. Clinical outcomes
of endoscopic submucosal dissection for coloerctal tumors: a large multicenter retrospective study from the Hiroshima GI Endoscopy Research Group.
Gastrointest Endosc 2018;87:714–22.
[23] Barret M, Lepiliiez V, Coumaros D, Chaussade S, Leblanc S, Ponchon T, et al.
The expansion of endoscopic submucosal dissection in France: a prospective
nationwide survey. UEGJ 2017;5:45–53.
Please cite this article in press as: Maselli R, et al. Endoscopic submucosal dissection: Italian national survey on current practices, training
and outcomes. Dig Liver Dis (2019), https://doi.org/10.1016/j.dld.2019.09.009