This is the second part of a two-part guideline from the European Society of Gastrointestinal
Endoscopy (ESGE) that covers the endoscopic management of superficial nonampullary
tumors of the duodenum. The companion guideline gives guidance on ampullary tumors.
Abbreviations
APC:
argon plasma coagulation
CA-EGD:
cap-assisted esophagogastroduodenoscopy
CT:
computed tomography
EMR:
endoscopic mucosal resection
ERCP:
endoscopic retrograde cholangiopancreatography
ESD:
endoscopic submucosal dissection
ESGE:
European Society of Gastrointestinal Endoscopy
EUS :
endoscopic ultrasound
EUS-BD:
endoscopic ultrasound-guided biliary drainage
EUS-FNA/B :
endoscopic ultrasound fine-needle aspiration/biopsy
FAP:
familial adenomatous polyposis
FTRD:
full-thickness resection device
GI:
gastrointestinal
GRADE:
Grading of Recommendations Assessment, Development and Evaluation
IDUS :
intraductal ultrasound
IHC :
immunohistochemistry
MRCP:
magnetic resonance cholangiopancreatography
NBI:
narrow band imaging
OR:
odds ratio
OTS:
over-the-scope
RCT:
randomized controlled trial
RFA:
radiofrequency ablation
SEMS:
self-expandable metal stent
SNADT :
superficial nonampullary duodenal tumor
U-EMR:
underwater endoscopic mucosal resection
1 Introduction
Superficial nonampullary duodenal tumors (SNADTs) are less frequently observed compared
with adenomas in the other areas of the gastrointestinal (GI) tract but recent studies
have shown a gradual increase in incidence of these lesions [1]. This increase could be explained by some environmental factors but also by better
accuracy of gastroscopy and new endoscopic detection technologies. Endoscopy has taken
the main role in management of these lesions, particularly in a curative setting.
Nevertheless, diagnostic and therapeutic strategies need to be clearly defined.
Lesions associated with predisposing genetic syndromes, including familial adenomatous
polyposis (FAP), or of submucosal or neuroendocrine origin, will not be discussed
here as they are considered in another Guideline from the European Society of Gastrointestinal
Endoscopy (ESGE) [2]. While the indications for endoscopic treatment and follow-up may be different between
the sporadic and polyposis-related forms, the statements regarding diagnosis, evaluation,
technical modalities of SNADT treatment, and management of complications are similar.
2 Methods
ESGE commissioned this Guideline (Guideline Committee Chair, J.v.H) and appointed
a guideline leader (G.V.) who invited the listed authors to participate in the project
development. The key questions were prepared by the guideline leader on two topics
(endoscopic management of ampullary tumors and of preneoplastic duodenal lesions)
and then approved by the other project members. The coordinating team established
task force subgroups, each with its own leader, that were assigned key questions (see
Appendix 1s, online-only Supplementary Material).
Each task force performed a systematic literature search to prepare evidence-based
and well-balanced statements on their assigned key questions. The literature search
was performed for English-language articles in MEDLINE, Embase, and the Cochrane database,
focusing on meta-analyses and fully published prospective studies, particularly randomized
controlled trials (RCTs), performed in humans. Retrospective analyses and pilot studies
were also included if they addressed topics not covered in the prospective studies.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system
was adopted to define the strength of recommendation and quality of evidence. Each
task force proposed statements on their assigned key questions which were discussed
during a web meeting in July 2020. Literature searches were re-run in September 2020.
This time-point should be the starting point in the search for new evidence for future
updates to this Guideline.
In September 2020, a draft prepared by G.V. was sent to all group members for review.
The draft was also reviewed by two external reviewers and then sent for further comments
to the ESGE national societies and individual members. After agreement on a final
version, the manuscript was submitted to the journal Endoscopy for publication. All authors agreed on the final revised version.
This Guideline was issued in 2021 and will be considered for review in 2025, or sooner
if new and relevant evidence becomes available. Any updates to the Guideline in the
interim period will be noted on the ESGE website: http://www.esge.com/ esge-guidelines.html.
3 Diagnosis of superficial nonampullary duodenal tumors
3 Diagnosis of superficial nonampullary duodenal tumors
3.1 Epidemiology, histology, presentation, and predictive factors
ESGE recommends that all duodenal adenomas should be considered for endoscopic resection
as progression to invasive carcinoma is highly likely.
Strong recommendation, low quality evidence.
ESGE recommends performance of a colonoscopy, if that has not yet been done, in cases
of duodenal adenoma.
Strong recommendation, low quality evidence.
The prevalence of SNADTs is relatively low, reported as between 1.0 % to 1.5 % in
retrospective series [3]
[4] and 4.6 % in a prospective one [5]. Among these and another retrospective series, the overall prevalence of adenoma
ranged only from 0.03 to 0.4 % [3]
[5]
[6].
In contrast to ampullary tumors, duodenal adenomas are less often sporadic, being
associated in 60 % of cases with FAP [7]. The other predisposing genetic syndrome is MUTYH-associated polyposis in which the prevalence of duodenal adenomas is estimated to
be 17 %–25 % of patients [8]. Some independent predictive factors for sporadic duodenal adenomas have recently
been determined, including current smoking (odds ratio [OR] 3.35, 95 %CI 1.79–6.30),
Barrett’s esophagus (OR 4.23, 95 %CI 2.17–8.25), fundic gland polyp (OR 2.29, 95 %CI
1.29–4.06), and malignant disease (OR 2.84, 95 %CI 1.57–5.15) [9]. When the patient presents with predictive factors, a careful gastroscopic examination
of the whole duodenum must be carried out with fulfilment of the appropriate quality
criteria [10].
In addition, a meta-analysis of several case–control studies (24 studies, 37 152 participants)
has suggested an association between sporadic duodenal adenoma and colorectal adenoma
[11]. The largest case–control study on the subject, published after the above meta-analysis,
included 203 277 patients (537 with duodenal adenomas) who underwent upper and lower
gastrointestinal endoscopy. Patients with duodenal adenoma showed a significantly
higher prevalence of all types of colonic adenomas (OR 2.65, 95 %CI 2.16–3.25), advanced
colonic adenomas (OR 4.30, 95 %CI 3.24–5.70), and colorectal cancer (OR 3.13, 95 %CI
1.38–7.12), without location preference between left and right colon [12].
Most of the lesions are diagnosed incidentally during a gastroscopy, with initial
histopathological findings of low grade dysplasia [13]. After a follow-up of 6 months, 20.9 % (9/43) of low grade dysplasia adenomas showed
progression to high grade dysplasia, including 4.7 % in situ carcinomas [13]. High grade dysplasia diagnosis at first biopsy and a lesion diameter of ≥ 20 mm
are significantly predictive of progression to adenocarcinoma [13].
The progression from adenoma to adenocarcinoma is of two types [14]. In the first, intestinal-type lesions in proximal and distal duodenum follow the
adenoma–carcinoma sequence, similarly to carcinogenesis in the colon. Secondly, progression
of a de novo gastric type, including gastric foveolar-type or pyloric gland adenoma,
is independent of the usual Wnt/β-catenin pathway and is associated with gastric duodenal
metaplasia in the proximal segment (bulb). The gastric-type lesion is more frequently
diagnosed as carcinoma, with a tendency to poorer prognosis [15]. The intestinal-type progression is associated with classic adenomas, most of which
are located in the second part of the duodenum and are the most common form of presentation.
3.2 Endoscopic assessment, biopsy, and staging
ESGE recommends the use of the cap-assisted method when the location of the minor
and/or major papilla and their relationship to a duodenal adenoma is not clearly established
during forward-viewing endoscopy.
Strong recommendation, moderate quality evidence.
ESGE recommends the routine use of a side-viewing endoscope when a laterally spreading
adenoma with extension to the minor and/or major papilla is suspected.
Strong recommendation, low quality evidence.
ESGE suggests the use of magnifying chromoendoscopy for endoscopic diagnosis and staging
of duodenal lesions.
Weak recommendation, low quality evidence.
ESGE suggests that if endoscopic features are suggestive of superficial duodenal adenoma,
the use of biopsy for histological assessment should be limited prior to endoscopic
resection, since its additional diagnostic yield might be limited and resection might
be compromised.
Weak recommendation, low quality evidence.
The macroscopic presentation for sporadic duodenal adenoma is mainly milk-white or
reddish mucosa ([Fig. 1]) [16]
[17], and the morphology of the lesion is usually 0-IIa in the Paris classification [17]
[18]
[19]. The associations between the macroscopic type or the tumor size and malignancy
have been analyzed with conflicting results [1]
[13]
[20]
[21]. Nevertheless, Paris 0-IIc or III lesions with ulcerated forms and loss of superficial
pit pattern remain potentially significantly more likely to have an unfavorable outcome
and to be invasive and therefore more likely to lead to a definitive histological
finding.
Fig. 1 Sporadic duodenal adenoma: different macroscopic presentations. a Type 0-Is with milk-white mucosa; b Type 0-IIa with reddish mucosa; c Type 0-IIa with milk-white mucosa.
Evaluation of the extent of the SNADT may require some technical adaptations. The
use of a transparent cap on the tip of a forward-viewing endoscope (cap-assisted esophagogastroduodenoscopy
[CA-EGD]), for the duodenal folds and the area of the ampulla, enhances visualization
and targeting of lesions especially at the genu superius [22]. It also has been shown to effectively visualize the ampulla, with failure rates
of only 3 %–9 % [23]
[24]
[25]
[26]. Although CA-EGD appears significantly better than standard gastroscopy to explore
the papilla, comparative studies of CA-EGD versus side-viewing duodenoscopy had conflicting
results [25]
[26]
[27]. CA-EGD can therefore be used when the location of the papilla and its relationship
to the duodenal adenoma have not been definitively established. However, the use of
a side-viewing endoscope remains essential when extension of the lesion to the papilla
is suspected.
Indigo carmine chromoendoscopy has consistently been shown to increase detection rates
especially in high risk populations [28]
[29]
[30]
[31]. The use of narrow-band imaging (NBI) also improved the detection capability for
duodenal adenomas in a prospective study in patients with FAP [21]. The magnifying NBI criteria for microsurface structures and microvessel patterns
were reported to be useful to distinguish neoplastic from non-neoplastic lesions [32]
[33]. Considering the pit and vascular patterns in the largest retrospective study of
107 patients (114 lesions), and using a propensity score-matching analysis, NBI showed
sensitivity of 92 % (95 %CI 86–98), specificity 79 % (95 %CI 67–91), positive predictive
value 87 % (95 %CI 80–95), negative predictive value 87 % (95 %CI 77–97), and accuracy
87 % (95 %CI 81–94), with good interobserver agreement (κ coefficient 0.60–0.76) [33]. NBI was also useful for distinguishing between low and high grade dysplasia and
adenocarcinoma [34]
[35]
[36]). Crystal violet staining appears more accurate for differentiating adenoma with
low grade dysplasia from high grade dysplasia and adenocarcinoma when compared to
white light endoscopy [37]. Nevertheless, it failed to show any significant superiority in a comparative retrospective
study with NBI chromoendoscopy; the latter may be preferable because it is a simple,
less time-consuming procedure [38].
Recent studies have reported limited diagnostic performance for endoscopic duodenal
biopsy sampling [1]
[32]
[33]
[39]
[40]. A multicenter case series of 364 patients with histologically proven adenoma found
significantly higher diagnostic performance for preoperative endoscopic assessment
(with high resolution endoscopy) compared to biopsies, for sensitivity (77 % vs. 58 %,
P < 0.01) and accuracy (75 % vs. 68 %, P = 0.03) [1]. In a retrospective analysis of 95 resected duodenal adenomas, the sensitivity of
biopsies was only 37.5 % (95 %CI 18.8–59.4) for prediction of final histologic diagnosis
of carcinoma [40]. Furthermore, preoperative biopsies can induce submucosal fibrosis that makes endoscopic
resection more difficult and increases the risk of adverse events. Thus, Kinoshita
et al. [40] noted a conversion from endoscopic mucosal resection (EMR) to endoscopic submucosal
dissection (ESD) because of the nonlifting sign in 24.6 % of cases, to which prior
biopsies may have contributed.
4 Endoscopic treatment of small (< 6 mm) duodenal adenomas
4 Endoscopic treatment of small (< 6 mm) duodenal adenomas
ESGE suggests cold snare polypectomy for small ( < 6 mm in size) nonmalignant duodenal
adenomas.
Weak recommendation, low quality evidence.
Traditionally, duodenal adenomas were removed by hot snare polypectomy. However, hot snare polypectomy has associated risks of delayed bleeding, post-polypectomy
syndrome, and perforation that are higher compared with those of the stomach and colon,
because of the thin and vascular walls of the duodenum [41]
[42].
Cold snare polypectomy is the preferred technique for removal of small duodenal adenomas
< 6 mm in size. The evidence for this was initially extrapolation from studies on
small colonic polyps [41]
[43]. Recently, increasing evidence is supporting the use of cold snare polypectomy for
small polyps in the duodenum, even in polyposis syndromes such as FAP [44]
[45]
[46]. In a prospective study of 30 patients, 39 lesions (mean [SD] size 3.9 [1.2 ] mm,
range 2 –6 mm) were removed via cold forceps polypectomy (9 lesions in 8 patients)
or cold snare polypectomy (30 lesions in 22 patients) [47]. The en bloc resection rate was 77.8 % for cold forceps polypectomy and 96.7 % for
cold snare polypectomy. No delayed bleeding or perforation occurred, and the recurrence
rate was 0 % at 3 months [47].
5 Endoscopic treatment of large duodenal adenomas
5 Endoscopic treatment of large duodenal adenomas
5.1 Duodenal EMR in management of large adenomas
ESGE recommends EMR as the first-line endoscopic resection technique for nonmalignant
large nonampullary duodenal adenomas.
Strong recommendation, moderate quality evidence.
The largest prospective study on EMR of duodenal adenomas included 110 patients with
118 lesions (mean size 15 mm, range 4–70) and showed a complete resection rate of
94.1 % of lesions [48]. Adverse events were noted in 22.9 % (mainly delayed bleeding in 18.6 % of lesions)
and major adverse events occurred in 15.3 % of all lesions with a procedure-related
mortality of 1.7 % (n = 2 patients) [48]. Nearly all other studies of duodenal EMR are retrospective and, when compared to
EMR for similar-sized lesions elsewhere in the gastrointestinal tract, show higher
rates of complications such as intraprocedural bleeding, post-procedural bleeding,
and perforation [19]
[42]
[49]
[50]
[51]. In a systematic review and meta-analysis that included 440 patients with 485 duodenal
nonampullary adenomas from 14 retrospective studies published up to May 2015, the
mean polyp size ranged from 13 to 35 mm and complete endoscopic resection by polypectomy
or EMR was achieved in 93 % of lesions [52]. The overall bleeding rate including intra- and post-procedural bleeding was 16 %
and the pooled delayed bleeding rate was 5 %. The rate of perforation was 1 % and
the rate of surgical intervention because of noncurative EMR or adverse events was
2 %. There was no procedure-related mortality [52].
In more recent retrospective studies, high rates of complete endoscopic resection
(90.5 %–96.1 %) have been obtained with EMR, whereas the adverse event rates ranged
from 2 % to 24.4 % [17]
[19]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]. Increasing lesion size was associated with reduced rates of en bloc resection as
well as increased rate of adverse events [50]
[53]
[55]
[56]
[57]
[62]. However, the majority of duodenal EMR adverse events can be safely managed endoscopically
[54]
[55]
[60].
[Table 1] summarizes the outcomes from recent EMR studies and the findings of the abovementioned
systematic review [52].
Table 1
Outcomes of endoscopic mucosal resection (EMR) for superficial nonampullary duodenal
lesions in recent literature.
|
First author, year
|
Participants, n (Lesions, n), Study design
|
En bloc resection, n/N (%)
|
Complete resection[1], n/N (%)
|
Overall morbidity, n/N (%)
|
Residual adenoma[2], n/N (%)
|
Recurrence, n/N (%)
|
|
Probst, 2020 [48]
|
110 (118), Prospective
|
46/118 (39.0 %)
|
111/118 (94.1 %)
|
27/118 (22.9 %)
|
19/93 (20.4 %)
|
NA
|
|
Kuroki, 2020 [17]
|
163 (171), Retrospective[3]
|
152/157 (93 %)
|
141/157 (90 %)
|
9/157 (5.7 %)
|
NA
|
2/157 (1 %)
|
|
Na, 2020 [61]
|
92 (95), Retrospective[4]
|
49/59 (83.1 %)
|
48/59 (81.4 %)
|
7/59 (11.9 %)
|
NA
|
0/59 (0)
|
|
Zou, 2019 [58]
|
54 (54), Retrospective[5]
|
8/21 (38.1 %)
|
NA
|
2/21 (9.6 %)
|
NA
|
4/21 (19 %)
|
|
Tomizawa, 2018 [55]
|
142 (166), Retrospective
|
88/166 (53 %)
|
130/142 (92 %)
|
18/166 (11 %)
|
NA
|
32/142 (23 %)
|
|
Valerii, 2018 [54]
|
68 (75), Retrospective
|
42/75 (56 %)
|
75/75 (100 %)
|
16/75 (21.3 %)
|
9/68 (14.5 %)
|
6/68 (10.9 %)
|
|
Klein, 2017 [63]
|
102 (102), Retrospective
|
NA
|
95/102 (93.1 %)
|
19/102 (18.6 %)
|
14/79 (17.7 %)
|
6/55 (10 %)
|
|
Valli, 2017 [56]
|
78 (78), Retrospective
|
28/78 (35.9 %)
|
71/78 (91 %)
|
9/78 (11.6 %)
|
7/78 (9 %)
|
0/78 (0)
|
|
Jamil, 2017 [53]
|
42 (49), Retrospective
|
10/49 (20.4 %)
|
38/42 (90.5 %)
|
10/59 (16.9 %)
|
4/42 (9.5 %)
|
0/32 (0)
|
|
Navaneethan, 2016 [52]
|
440 (485), Systematic review
|
–
45 %
|
–
93 %
(95 %CI 89–97 %)
|
–
Delayed bleeding: 5 %
(95 %CI 2 %–7 %)
Perforation: 1 %(95 %CI 1 %–3 %)
|
NA
|
–
15 %
(95 %CI7 %–23 %)
|
NA, Not available; 95 %CI, 95 % confidence interval.
1 Complete resection was defined as a complete removal of the lesion after the first
endoscopic treatment session.
2 Residual adenoma was defined when tumoral tissue was confirmed by histology at the
first endoscopic follow-up.
3 157 lesions only treated by EMR.
4 59 lesions only treated by EMR.
5 21 patients only treated by EMR.
5.2 Emerging and alternative EMR techniques
Underwater EMR (U-EMR) may improve duodenal EMR outcomes [59]
[64]
[65]. The filling of the lumen with water in U-EMR would theoretically limit the risk
of ensnaring the muscularis propria layer. In a recent retrospective Japanese study,
104 patients underwent U-EMR for duodenal nonampullary adenomas of size ≤ 20 mm [59]. The complete resection rate without conversion to ESD was higher with U-EMR (87 %)
compared with conventional EMR (70 %) (P < 0.01). There was no difference in adverse event rates between the two techniques
[59].
Recently, the efficacy and safety of piecemeal cold snare EMR for large duodenal adenomas
were evaluated in small retrospective series [66]
[67]. In a study of 15 patients with lesions ranging from 10 to 60 mm in size, the technical
success rate was 100 % with no cases of perforation and with only one case of delayed
bleeding in a patient who was on warfarin [67].
5.3 Duodenal ESD in management of large adenomas
ESGE recommends that ESD for duodenal adenomas is an effective resection technique
only in expert hands.
Strong recommendation, low quality evidence.
ESGE recommends that duodenal ESD should be reserved for select indications at expert
ESD centers.
Strong recommendation, low quality evidence.
ESD for adenomas in the duodenum is more challenging than in other locations such
as the esophagus stomach, or rectum. In expert Asian centers, larger lesions (> 20 mm)
are often considered for ESD at the outset [68], whereas in Western centers this technique is usually reserved for cases of suspected
superficial submucosal invasion, or for nonmalignant lesions that are nonlifting due
to de novo submucosal fibrosis or secondary to previous biopsy or incomplete resection.
However, duodenal ESD is associated with a high incidence of adverse events, even
in experienced centers [69]
[70]
[71]
[72]. Perforation incidences of 13 %–50 % have been reported [39]
[73]
[74]
[75]
[76]
[77]
[78]
[79].
Since a previous ESGE Guideline that recommended against routine use of ESD in the
duodenum because of its high risk of perforation [80], further series have been published, mainly from expert Asian centers. En bloc resection
rates of higher than 90 % have been reported, even in lesions larger than 20 mm [74]
[75]. Nevertheless, more limited duodenal ESD data from Europe are available [20]
[81]
[82], and the largest series reported a disappointing en bloc resection rate of 29.7 %,
with a 14.7 % recurrence rate [20]. Furthermore, comparative data analysis between EMR and ESD showed better R0 rates
for large lesions with ESD but no differences in long-term outcomes and survival [20]
[61]
[74]
[76]
[82]. However, intraprocedural perforation (up to 30 %) and delayed perforation was significantly
associated with ESD [20]
[61]
[75]
[77]
[83]. Therefore, in most cases, the focus of duodenal endoscopic resection should primarily
be on safety, rather than on achieving en bloc or R0 resection. The superior safety
profile of EMR compared to ESD lends greater weight to EMR’s being the first-line
technique for duodenal adenomas in most cases, despite the higher recurrence rate
with EMR, that may require further endoscopic therapy.
[Table 2] shows comparative results for EMR and ESD of superficial nonampullary duodenal adenomas.
Table 2
Retrospective comparative results of endoscopic mucosal resection (EMR) and endoscopic
submucosal dissection (ESD) for treatment of superficial nonampullary duodenal adenomas.
(Statistically significant values are in bold.)
|
First author, year
|
|
EMR, n/N (%)
|
ESD, n/N (%)
|
P value
|
|
Na, 2020 [61]
|
Complete resection
|
48/59 (81.4 %)
|
8/11 (80 %)
|
> 0.99
|
|
Morbidity
|
7/59 (11.9 %)
|
5/11 (45.5 %)
|
0.03
|
|
Recurrence
|
0
|
0
|
1
|
|
Esaki, 2020 [83]
|
Complete resection
|
20/28 (71.4 %)
|
25/28 (83.3 %)
|
0.18
|
|
Morbidity
|
1/28 (3.6 %)
|
5/28 (17.9 %)
|
0.19
|
|
Recurrence
|
1/28 (3.6 %)
|
0/28 (0)
|
1
|
|
Yahagi, 2018 [75]
|
Complete resection
|
123/146 (82.2 %)
|
148/174 (85.1 %)
|
0.65
|
|
Morbidity
|
|
|
|
|
|
2/146 (1.4 %)
|
9/174 (5.2 %)
|
0.072
|
|
|
1/146 (0.68 %)
|
27/174 (15.5 %)
|
< 0.001
|
|
Recurrence
|
NA
|
NA
|
–
|
|
Pérez-Cuadrado-Robles, 2018 [20]
|
Complete resection
|
43/129 (35.5 %)
|
7/37 (19.4 %)
|
0.069
|
|
Morbidity
|
|
|
|
|
|
12/129 (9.3 %)
|
3/37 (8.1 %)
|
0.823
|
|
|
3/129 (2.3 %)
|
6/37 (16.2 %)
|
0.001
|
|
Recurrence
|
17/129 (16.7 %)
|
5/37 (14.7 %)
|
0.788
|
|
Hoteya, 2017 [77]
|
Complete resection
|
33/55 (60 %)
|
65/74 (87.8 %)
|
NA
|
|
Morbidity
|
5/55 (9 %)
|
22/74 (29.7 %)
|
NA
|
|
Recurrence
|
2/55 (3.6 %)
|
0/74 (0)
|
NA
|
NA, not available.
5.4 Alternative modalities to EMR or ESD for duodenal adenomas
ESGE suggests that, in expert hands, endoscopic full-thickness resection could be
an alternative to surgery or ESD for select cases of nonlifting duodenal adenomas
up to 25 mm in size without signs of deep submucosal invasion.
Weak recommendation, very low quality evidence.
Endoscopic full-thickness resection applying an over-the-scope (OTS) clip-based technique
(i. e., with a full-thickness resection device [FTRD]) has been used for the resection
of difficult and nonlifting duodenal lesions [84]
[85]
[86]
[87]. Currently, limited data from retrospective studies and small case series have shown
technical success rates of 85 %–100 %, high rates of complete resection of the target
lesion (75 %–80 %), and very low rates of major complications. However, these studies
included heterogeneous duodenal lesions, and the FTRD has some technical limitations
in the upper gastrointestinal tract (the large diameter of the bulky device makes
passage through the upper esophageal sphincter and the pylorus challenging). The device
size limits en bloc resection to lesions ≤ 25 mm in size [85]. Furthermore, a minimum distance of 20 mm is required between the lesion and the
major papilla, to avoid the risk of clipping and closing the bile duct or pancreatic
duct, with potentially severe consequences [85].
Recent small case series have demonstrated a good safety and efficacy profile for
combined laparoscopic and endoscopic surgery in patients with advanced duodenal adenomas
or early adenocarcinomas [88]
[89]
[90]
[91]
[92]. Ichikawa et al. [92] reported no local or distant recurrence at a median follow-up of 14 months in 10
patients with mucosal adenocarcinoma treated with combination laparoscopic and endoscopic
surgery. In a retrospective observational study by Ojima et al. [91], this technique showed no adverse events (0 %) compared to ESD (28 %). However,
larger prospective studies are needed to confirm these results.
5.5 Role of tumor-destruction techniques
ESGE suggests that an additive role for ablative or other tumor-destruction techniques
is minimal because of lack of efficacy.
Weak recommendation, low quality evidence.
Historically, several complementary tissue destruction techniques had been used for
nonampullary duodenal lesions. These included monopolar/bipolar coagulation, lasers
such as the Nd-YAG [93]
[94]
[95], photodynamic therapy [96], and cryotherapy [97]
[98]. However, most of these have been abandoned because of lack of efficacy or unacceptable
adverse events [95]
[96].
Argon plasma coagulation (APC) is still used [60]
[99]
[100]
[101], although it is not effective as a primary therapy, showing adenoma recurrence rates
of 39 %–75 % [7]
[102]
[103]
[104]. APC has been used as an adjunctive technique to eliminate residual adenoma when
technical difficulties resulted in incomplete endoscopic resection [99]
[100]
[104]
[105]
[106]
[107]
[108]
[109]
[110]
[111]. However, in one such study, the reported recurrence rate was high at 25.7 % [105]. In another study by Apel et al. [99], the use of APC for residual duodenal adenoma did not lead to eradication in most
of the lesions. However, a study by Alexander et al. [100] showed complete eradication of residual adenoma using APC in all 5 patients reported
in the study. Given these findings, a careful endoscopic surveillance is required.
5.6 Prevention of delayed adverse events after duodenal endoscopic resection
ESGE recommends using techniques that minimize adverse events such as immediate or
delayed bleeding or perforation. These may include piecemeal resection, defect closure
techniques, noncontact hemostasis, and other emerging techniques, and these should
be considered on a case-by-case basis.
Strong recommendation, low quality evidence.
ESGE recommends that the high adverse event rate with duodenal resection may be reduced
by mucosal defect closure techniques such as endoscopic clipping or OTS clipping,
and by noncontact hemostatic measures.
Strong recommendation, low quality evidence.
The evidence for routine prophylactic clip closure following duodenal EMR is limited.
Prophylactic through-the-scope clipping was associated with a significant reduction
in delayed bleeding (0 % vs. 22 %, P = 0.044) when compared to no prophylaxis, in a retrospective study involving 43 duodenal
EMR sessions [50]. In a prospective study using U-EMR for 31 duodenal adenomas of size ≤ 20 mm, clip
closure of the defect was performed for all lesions with no procedure-related adverse
events being reported [64]. However, the risk of perforation due to clip application and large resection sites
that cannot be fully closed are limiting factors, and therefore clips should be applied
carefully and their use considered on a case-by-case basis.
Noncontact hemostatic products have been successfully used to minimize bleeding following
duodenal EMR; however the evidence is still limited [112]
[113].
In the multivariate analysis of a recent case series of duodenal ESDs, lesion location
in the duodenal flexure, lesion size > 40 mm, and occupied duodenal circumference
of > 50 % were associated with increased adverse events [114]. In a recent large retrospective Japanese study involving 168 patients, the rate
of delayed adverse events after duodenal ESD was significantly reduced when the mucosal
defect was completely closed, compared with only partial closure or no closure (1.7 %
vs. 25 % vs. 15.6 %, respectively, P < 0.01) [115]. These data were confirmed by two more studies where delayed bleeding was effectively
prevented by prophylactic endoscopic closure of the defect [18]
[116]. Recently, closure of the defect by OTS clipping has also been shown to be effective
in reducing delayed adverse events after ESD [117]. Furthermore, the additional use of conventional through-the-scope clips, to cover
the inverted submucosa after defect closure with OTS clipping, was found to significantly
reduce the risk of delayed bleeding [118].
6 Follow-up, risk and management of recurrence after endoscopic duodenal resection
6 Follow-up, risk and management of recurrence after endoscopic duodenal resection
ESGE recommends that recurrences after endoscopic treatment for superficial nonampullary
duodenal lesions can be managed endoscopically, if this is deemed technically feasible
and in the absence of suspected malignancy.
Strong recommendation, low quality evidence.
ESGE suggests that the choice of endoscopic technique to manage recurrent adenoma
should be left to the discretion of the endoscopist, according to the morphology of
the lesion and patient characteristics.
Weak recommendation, very low quality evidence.
ESGE recommends endoscopic surveillance 3 months after the index treatment. In cases
of no recurrence, a further follow-up endoscopy should be done 1 year later. Thereafter,
surveillance intervals should be adapted to the lesion site, en bloc resection status,
and initial histological result.
Strong recommendation, low quality evidence.
Over a median follow-up period ranging from 6 to 72 months, the local recurrence rate
after EMR was 15 % (95 %CI 7 %–23 %) in the largest review of the literature [52]. Advanced histopathology, defined as the presence of villous changes (OR 4.86, 95 %CI
1.62–14.63) or high grade dysplasia, was shown to increase the risk of local recurrence
[52]
[56]
[62]. Similarly, increasing lesion size was associated with a higher recurrence rate
[19]
[52]
[55]
[63]
[106]. With regard to the techniques originally used to remove the lesion, no significant
difference in recurrence rate was observed between EMR versus ESD or EMR versus hybrid
ESD [18]
[81]. After a median follow-up of 6.5 months (2–125), Pérez-Cuadrado-Robles et al. [20] showed 5/37 recurrences (14.7 %) after ESD and 17/129 (16.7 %) after EMR (P = 0.788). Furthermore, there were no demonstrable differences in recurrence rates
between en bloc or piecemeal EMR in the largest review of duodenal EMR studies [52].
The available studies have shown that recurrent lesions are usually small in size
and can be successfully treated endoscopically in most cases by an expert endoscopist
[19]
[119]. In the review from Navaneethan et al., six studies reported the outcomes of managing
recurrent adenoma, and further endoscopic therapy was successful in 62 % (95 %CI 37 %–87 %)
[52]. In the absence of relevant comparative data, no specific endoscopic technique could
be preferentially recommended to manage adenoma recurrence.
Regarding the surveillance interval after index endoscopy, expert opinions are in
favor of a first endoscopy at 3–6 months. The evidence for this approach is limited,
but it has been recently supported by a prospective study showing that at 3 months,
residual or recurrent adenoma was noted in 20.4 % of patients who then had endoscopic
re-treatment [48]. Valerii et al. [54] retrospectively reported 15 recurrences in 62 lesions, with 9 of them (60 %) being
found at the first follow-up endoscopy performed 3 months after the initial endoscopic
treatment. A second surveillance endoscopy 1 year later seems to be advisable, if
no residual or recurrent adenoma has been detected during the first surveillance endoscopy
[41]
[48]
[52]
[120]. Subsequent surveillance intervals should then be individualized, taking into account
lesion factors (size, high grade dysplasia, or villous component) and patient factors
(age, comorbidities) [52]. Late recurrences are uncommon, but possible.
7 Role of surgery for nonmalignant sporadic duodenal adenomas
7 Role of surgery for nonmalignant sporadic duodenal adenomas
The literature on duodenal surgery for SNADT is limited and mainly consists of studies
on patients with FAP, as detailed in the ESGE Guideline for FAP [2]. For sporadic nonmalignant duodenal lesions, less invasive options such as transduodenal
excision and segmental duodenal resection are preferred compared with pancreaticoduodenectomy
or pancreas-sparing duodenectomy, as the less invasive approaches demonstrate lower
morbidity rates [121]
[122]
[123]
[124]. A retrospective study of 86 patients showed morbidity rates of 17 % after transduodenal
excision compared with 40 % and 45 % after pancreaticoduodenectomy and pancreas sparing
duodenectomy, respectively [121]. In three other retrospective studies, the morbidity rate for pancreaticoduodenectomy
was significantly higher compared to the less invasive transduodenal excision or segmental
duodenal resection [7]
[122]
[125]. However, a 5-year recurrence rate of 32 % after transduodenal excision for villous
adenomas is reported [121]. Therefore, postoperative endoscopic surveillance is mandatory after surgery, and
endoscopic resection of recurrences following surgery is still possible [125].
In a cohort of 121 patients with nonampullary duodenal lesions, 91 were treated by
EMR, as opposed to surgical therapy with pancreas-sparing duodenectomy [125]. The recurrence rate during follow-up was significantly higher in the EMR than in
the surgical group (32 % vs. 0 %, P < 0.001). However, there was a trend towards higher adverse event rates in the surgical
group than in the EMR group (26 % vs. 15 %), although it should be noted that larger
and more advanced lesions had been treated in the surgical group [125]. Other studies have also shown lower mortality and morbidity, shorter procedural
time and shorter hospital stay in endoscopically treated patients [7]
[118]
[122]
[124]. Therefore, while adenoma recurrence is low following pancreas-sparing duodenectomies,
the high morbidity and mortality associated with these procedures make them options
of last resort for most cases of sporadic duodenal adenoma [7]
[125].
Finally, in cases of confirmed duodenal malignancy, an oncological resection including
lymph node dissection, such as achieved by pancreaticoduodenectomy is required, whereas
pancreas-sparing duodenectomy and transduodenal excision are not oncological resections
and are reserved for premalignant lesions only.
Disclaimer
The legal disclaimer for ESGE guidelines [126] applies to this Guideline.
