Abbreviations
ARMS:
antireflux mucosectomy
CT:
computed tomography
EGJ:
esophagogastric junction
EMR:
endoscopic mucosal resection
ESD:
endoscopic submucosal dissection
ESGE:
European Society of Gastrointestinal Endoscopy
ESNM:
European Society of Neurogastroenterology and Motility
GERD:
gastroesophageal reflux disease
GI:
gastrointestinal
G-POEM:
gastric peroral endoscopic myotomy
GRADE:
Grading of Recommendations Assessment, Development, and Evaluation
LAPEC:
laparoscopically assisted percutaneous endoscopic cecostomy
LES:
lower esophageal sphincter
PEG:
polyethylene glycol
POEM:
peroral endoscopic myotomy
PPI:
proton pump inhibitor
RCT:
randomized controlled trial
SB knife Jr.:
Stag Beetle knife Junior
TIF:
transoral incisionless fundoplication
UEG:
United European Gastroenterology
Z-POEM:
Zenker’s POEM
This Guideline is an official statement of the European Society of Gastrointestinal
Endoscopy (ESGE). It provides guidance on the endoscopic management of Zenker’s diverticulum,
gastroesophageal reflux disease, intractable constipation, and Ogilvie’s syndrome.
The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system
was adopted to define the strength of recommendations and the quality of evidence.
1 Introduction
Therapeutic gastrointestinal (GI) endoscopy is rapidly evolving. Its role in the management
of motility disorders of the digestive tract is increasing. The purpose of this Guideline
is to provide guidance on various aspects of the endoscopic management of GI motility
disorders. This is the second of two parts of the guideline, and is dedicated to Zenker’s
diverticulum, gastroesophageal reflux disease (GERD), intractable constipation, and
Ogilvie’s syndrome. The first part, published as a separate manuscript, focused on
achalasia and gastroparesis.
2 Methodology
The ESGE commissioned this Guideline (Guideline Committee chair, J.v.H.) and appointed
a Guideline leader (B.W.); he identified six clinical conditions of abnormal GI motility
in which therapeutic endoscopy is one of the treatment possibilities: Zenker’s diverticulum,
achalasia, GERD, gastroparesis, intractable constipation, and Ogilvie’s syndrome.
These six areas were at a later stage agreed on by the Guideline committee members.
In March 2018, an email was sent out to several key opinion leaders in the field of
therapeutic endoscopy to identify potential Guideline committee members. Individual
ESGE members were informed about this Guideline and were asked to apply if they were
interested in participating with this Guideline. Three individual members (V.L.-Z.,
H.L., and F.P.) were selected based on their expertise and scientific output. In addition,
the European Society of Neurogastroenterology and Motility (ESNM) was approached for
collaboration and scientific input. As a result, the ESNM appointed on request four
Guideline committee members regarded as experts in the field of GI motility and therapy
(D.P., E.S., J.T., and R.T.). Finally, a Guideline committee was formed comprising
18 members, and covering the six areas of this guideline. Six task forces were created,
based on the six clinical conditions. Each task force had one or two task force leaders,
and each group member was assigned to one or more task forces (Appendix 1s, see online-only Supplementary Material). The kick-off meeting for this Guideline
was held during United European Gastroenterology (UEG) Week, on 21 October 2018, in
Vienna.
During a teleconference in November 2018, clinical questions were formulated for the
six clinical conditions. Subsequently, these clinical questions were translated into
research questions (Appendix 2s). The questions followed the PICO format (P, population in question; I, intervention;
C, comparator; and O, outcomes of interest) wherever appropriate. Subsequently, systematic
literature searches were done using Medline, Embase, and Cochrane library.
Evidence levels and recommendation strengths were assessed using the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) system [1]. Further details on the methodology of ESGE guidelines have been reported elsewhere
[2]. The results of data extraction are presented in Appendix 3s.
Available literature, draft recommendations, and strength of evidence were discussed
during a face-to-face meeting with all group members at Schiphol Airport, Amsterdam
on 12 April 2019.
In order to establish consensus-based recommendations, a modified Delphi process [3] was organized using an online voting platform (www.surveymonkey.com). Voting was based upon a five-point Likert scale (1, strongly disagree; 2, disagree;
3, neither disagree nor agree; 4, agree; 5, strongly agree). A recommendation was
approved if > 75 % of the members agreed (reflected by a Likert score of 4 – 5). In
total three iterations of the online voting process were needed to come to the final
document.
In January 2020, a draft prepared by B.W. was sent to all group members. After the
agreement of all group members had been obtained, the manuscript was reviewed by the
ESGE Guideline Committee Chair (J.v.H.) and two external reviewers, and was sent for
further comments to the ESGE national societies and individual members. After this,
it was submitted to Endoscopy for publication.
3 Zenker’s diverticulum
Zenker’s diverticulum is a pulsion diverticulum that develops in an area of weakness
of the posterior hypopharynx known as the Killian triangle (between the thyropharyngeus
and cricopharyngeal muscle fibers of the inferior constrictor). It is a relatively
uncommon condition, with an overall prevalence estimated to be between 0.01 % and
0.11 % in the American population; it occurs most frequently in men between their
7th and 8th decades [4]
[5]. Clinically, Zenker’s diverticulum may manifest with symptoms such as dysphagia
or regurgitation, and its associated complications [6].
The pathophysiology of Zenker’s diverticulum is not fully understood, but the most
widely proposed hypothesis is that a motor abnormity of the cricopharyngeus muscle
creates a high pressure zone that facilitates herniation of the hypopharyngeal mucosa
through the weak zone, the Killian triangle, resulting in diverticulum development
[7]
[8].
3.1 Diagnosis of Zenker’s diverticulum
ESGE recommends the use of barium swallow radiography with video fluoroscopy in the
evaluation of patients with (suspected) Zenker’s diverticulum.
Strong recommendation, very low quality of evidence, level of agreement 100 %.
ESGE suggests against the use of manometry as standard in the diagnostic work-up of
patients with Zenker’s diverticulum.
Weak recommendation, very low quality of evidence, level of agreement 100 %.
The diagnosis of Zenker’s diverticulum is suspected on the basis of clinical symptoms
and is confirmed by a barium swallow with video fluoroscopy. Although Zenker’s diverticulum
can be diagnosed by endoscopy, fluoroscopy is considered essential because it not
only provides information on pouch size, but will also give “dynamic” information
on regurgitation and aspiration. This is important in determining whether Zenker’s
diverticulum is the real cause of a patient’s symptoms. Studies on the clinical value
of manometry in Zenker’s diverticulum are missing. The working group however recommends
against the routine use of esophageal manometry in the work-up of patients with (suspected)
Zenker’s diverticulum. In individual cases (e. g. in small Zenker’s diverticulum),
esophageal manometry can be used to rule out other causes of similar symptoms.
3.2 Treatment options for Zenker’s diverticulum
3.2.1 First-line treatment
ESGE suggests flexible endoscopic treatment over open surgical treatment as first-line
therapy for patients with a symptomatic Zenker’s diverticulum of any size.
Weak recommendation, low quality of evidence, level of agreement 100 %.
Treatment is indicated for symptomatic Zenker’s diverticulum. Currently, there are
three main treatment options for Zenker’s diverticulum: open surgery (i. e. transcervical
diverticulectomy, diverticulopexy with myotomy of the cricopharyngeus muscle, or diverticular
inversion) [9]
[10]; rigid endoscopy (i. e. endoscopic stapling or CO2 laser treatment) [11]
[12]; and flexible endoscopy. The key common intervention in all three options is division
of the cricopharyngeus muscle that forms the septum between esophagus and the pouch.
The goal of treatment is to reduce the size of the diverticulum and improve pharyngeal
motor function, thus improving the symptoms of dysphagia and regurgitation.
Flexible endoscopic septum division involves the use of a flexible endoscope to carry
out septal myotomy [13]. Various incision techniques have been described for cutting the septum that contains
the cricopharyngeus muscle. The single-incision technique involves a midline incision
of the cricopharyngeus muscle with the option of clipping the base [14]. The double-incision technique allows a wider septum to be dissected. It involves
creating two incisions that are 1 cm apart from each other and the septum in between
is resected using a snare before the base is clipped [15].
There are no prospective comparative studies between surgery (by rigid endoscopic
or open approach) and flexible endoscopic treatment. One large retrospective study
by Shahawy et al. compared 36 patients treated by endoscopic septotomy with 31 patients
treated by diverticulectomy and myotomy, and found dysphagia recurrence in 39 % vs.
0 % (P = 0.001) at 2 months in the endoscopic vs. surgical treatment groups, respectively,
with 13 % vs. 31 % complication rates after each treatment (P = 0.08) [16]. Two large systematic reviews and meta-analyses involving 3079 and 596 patients
concluded that clinical success rates were significantly different, at 82 % – 87 %
with the endoscopic approach vs. 94 % – 96 % with the open surgical approach [17]
[18]. The complication rate was 7 % – 9 % with the endoscopic treatment vs.11 % – 15 %
with the open surgical approach.
Of note, most data from the literature mentioning endoscopic treatment for Zenker’s
diverticulum actually refer to laser or stapler septotomy using a rigid endoscope
and performed by an ENT surgeon. This is important because rigid endoscopy is not
always possible in elderly patients, with technical treatment failures of 6 % – 7 %
[17].
Most of the relevant data on the efficacy and safety of flexible endoscopic septotomy
for the treatment of Zenker’s diverticulum are summarized in the meta-analysis from
Ishaq et al. [19]; however, for most of this data, there is no direct comparison to surgical treatment.
In this work, including 813 patients, the pooled success rate of flexible endoscopic
septotomy was 91 %, with an 11.3 % adverse event rate and 11 % recurrences. The limitations
of surgery and rigid endoscopy, such as the need for general anesthesia and the high
rate of intraoperative abandonment owing to restricted neck mobility in the elderly,
combined with the seemingly higher complication rates of surgery with comparable success
rates have led to our recommendation on the use of flexible endoscopic techniques
as the first-line therapy for Zenker’s diverticulum.
3.2.2 Recurrent Zenker’s diverticulum
ESGE suggests treatment by flexible endoscopy for recurrent Zenker’s diverticulum.
Weak recommendation, low quality of evidence, level of agreement 100 %.
Regardless of the treatment modality used, recurrence of Zenker’s diverticulum is
not uncommon. Predictors of symptom relapse that occurs within 48 months of endoscopic
therapy include: pretreatment Zenker’s diverticulum size (≥ 50 mm), post-treatment
Zenker’s diverticulum size (≥ 10 mm), and the length of the septotomy (≤ 25 mm) [20].
Endoscopic management of recurrence after surgery or endoscopic stapling can be particularly
challenging. No comparative studies have been carried out between surgery (endoscopic
or open approaches) and flexible endoscopic treatment as therapy for pretreated patients
with Zenker’s diverticulum.
Two small retrospective studies involving 20 and 18 patients reported on the feasibility
of rigid endoscopic treatment using a stapler for recurrent Zenker’s diverticulum
[21]
[22]. They reported a short-term clinical remission rate of 81 % – 90 %, with a 20 % – 28 %
complication rate after endoscopic therapy, and 5 % recurrence rate. Antonello et
al. reported on the feasibility, safety, and effectiveness of flexible endoscopic
septotomy for recurrent Zenker’s diverticulum in 25 patients, using a diverticuloscope
and a septum incision or snare resection of the cricopharyngeus muscle, with similar
outcomes when compared with data from 34 treatment-naïve patients treated within the
same timeframe: the success, recurrence, and complication rates in naïve vs. recurrent
patients were 84 % vs. 82 %, 24 % vs. 15 %, and 8 % vs. 8.8 %, respectively [15]. In their retrospective study using a needle-knife and diverticuloscope (n = 134),
Huberty et al. reported recurrence rates of 23.1 %; of those who underwent repeat
treatment (n = 23), 78.3 % achieved symptom remission after redo myotomy [14].
Therefore, although the data are limited, flexible endoscopic septotomy appears to
perform equally well in recurrent Zenker’s diverticulum and treatment-naïve Zenker’s
diverticulum.
3.3 Flexible endoscopic treatment of Zenker’s diverticulum
3.3.1 Use of a diverticuloscope
ESGE suggests that it is left to the endoscopist’s discretion whether or not to use
a diverticuloscope when performing a flexible endoscopic septotomy for Zenker’s diverticulum.
Weak recommendation, low quality of evidence, level of agreement 100 %.
In one retrospective series, diverticuloscope-assisted treatment success was reported
to be higher than cap-assisted treatment [23]. In a meta-analysis by Ishaq et al., however, overall use of a diverticuloscope
had no impact on success or complications [19].
3.3.2 Minimum size of Zenker’s diverticulum
ESGE suggests symptomatic Zenker’s diverticula of any size are amenable to flexible
endoscopic treatment, although the usefulness of a diverticuloscope remains uncertain
for Zenker’s diverticula < 2 cm.
Weak recommendation, very low quality of evidence, level of agreement 100 %.
To our knowledge, no study has addressed the specific question of the minimum size
of Zenker’s diverticulum that is required for flexible endoscopic treatment. Published
case series on flexible endoscopic septotomy have included patients with diverticula
of mean size 20 – 50 mm [19]), with a possible optimal efficacy of endoscopic treatment for Zenker’s diverticula
between 30 and 50 mm in size [20].
Although most endoscopic studies have included patients with Zenker’s diverticula
measuring between 20 and 50 mm, there is no minimum size for symptomatic Zenker’s
diverticula to be considered amenable to endoscopic treatment. If the size is below
20 mm, however, the usefulness of a diverticuloscope is questionable.
3.3.3 Emerging endoscopic techniques for the treatment of Zenker’s diverticulum
ESGE recommends that emerging treatments for Zenker’s diverticulum, such as Zenker’s
peroral endoscopic myotomy (Z-POEM) and tunneling, be considered as experimental;
these treatments should be offered in a research setting only.
Strong recommendation, low quality of evidence, level of agreement 100 %.
New, alternative strategies for treating Zenker’s diverticulum by means of flexible
endoscopy are emerging. For instance, tunneling techniques used to cut the lower esophageal
sphincter (LES) in patients with achalasia (peroral endoscopic myotomy; POEM) or the
pylorus in gastroparesis (gastric peroral endoscopic myotomy; G-POEM) have recently
been applied to Zenker’s diverticula as well. Yang et al. collected data on 75 patients
treated by Zenker’s POEM (Z-POEM) across 10 centers and found a technical success
rate of 97 %, complication rate of 6.7 % (1 bleed and 4 perforations – all managed
conservatively), clinical success rate of 92 %, and observed only one recurrence after
a median follow-up of 10 months [24]. To date, the reported studies on alternative endoscopic treatments for Zenker’s
diverticulum have mainly consisted of case reports and series that lack long-term
follow-up data, with strong publication bias and possible underestimation of complication
rates. More studies are needed to define their role in the management of Zenker’s
diverticulum.
3.3.4 Use of CO2 during endoscopic Zenker’s diverticulum treatment
ESGE recommends routine use of CO2 in the endoscopic treatment of Zenker’s diverticulum.
Strong recommendation, very low quality evidence, level of agreement 100 %.
Although there are no comparative data in Zenker’s diverticulum, there is a sufficient
body of evidence in a relatively comparable treatment modality, namely POEM for achalasia,
that CO2 reduces the risk of subcutaneous emphysema. In Zenker’s diverticulum, once the cricopharyngeus
muscle has been dissected, the only posterior barrier to the superior mediastinum
is the buccopharyngeal fascia. CO2 is reabsorbed more quickly than room air and its use reduces the risk of gas-related
complications, such as pneumomediastinum and subcutaneous emphysema.
3.3.5 Use of prophylactic antibiotics
ESGE does not recommend routine administration of prophylactic antibiotics before
or after endoscopic septotomy for Zenker’s diverticulum.
Strong recommendation, low quality of evidence, level of agreement 92.9 %.
In a meta-analysis by Ishaq et al., 7/20 studies on conventional endoscopic treatment
of Zenker’s diverticulum used prophylactic antibiotics. Meta-regression analysis for
overall safety showed that prophylactic administration of antibiotics was not associated
with a reduction in complications [19].
3.3.6 Extent of myotomy
ESGE recommends performing a complete myotomy of the cricopharyngeus muscle when performing
endoscopic septotomy.
Strong recommendation, low quality of evidence, level of agreement 93.8 %.
All expert endoscopists involved in the treatment of Zenker’s diverticulum by flexible
endoscopy strongly advocate a full transection of the cricopharyngeus muscle. Direct
evidence from the literature to support this is lacking; however, from a pathophysiological
standpoint, a full myotomy of the cricopharyngeus muscle is essential to prevent the
recurrence of symptoms. The value of cutting deeper is controversial.
Costamagna et al. reported failure at 6 months if the length of the septotomy was
< 2.5 cm or the pretreatment pouch was > 5 cm, and failure at 48 months if the septotomy
length was < 2.5 cm or the post-procedure Zenker’s diverticulum size > 10 cm [20]. However, the authors’ measurement of septotomy length is debatable as they measured
pouch size before and after treatment using a marked catheter. They extrapolated that
the pouch size is equal to the septum length, but there is no peer evidence to support
this assumption.
3.3.7 Use of clips at the base of the septotomy
ESGE suggests that the decision to deploy clips at the base of the septotomy should
be dictated by endoscopist practice or clinical need (bleeding or suspected perforation).
Weak recommendation, low quality of evidence, level of agreement 100 %.
Clips are widely used at the base of the septotomy by the majority of endoscopists,
despite there being no evidence of their impact on adverse events, such as bleeding
or perforation. In a recent meta-analysis by Ishaq et al., six studies deployed clips
during the procedure but meta-regression analysis showed this had no impact on adverse
events, such as perforation [19].
3.3.8 Endoscopic knives and electrocoagulation settings
Almost every kind of endoscopic submucosal dissection (ESD) device has been used to
treat Zenker’s diverticulum. Early work was done by Ishioka with the needle-knife papillotome [25]. The advantages of the needle-knife include its low cost and easy availability,
but its disadvantages include downward cutting, which is linked with complications.
The HookKnife (Olympus, Tokyo, Japan) was originally designed for ESD. The tip of
the knife is bent at a right angle; with the rotatable “hook” measuring 1.3 mm and
the arm measuring 4.5 mm. This design enables the cricopharyngeal muscle fibers to
be isolated, pulled upwards, and then cut. Theoretically, the upwards pull of the
septal fibers minimizes perforation risk. Repici et al. reported a complication rate
of 6.3 % and overall success rate of 90.6 % for HookKnife myotomy [26]. Similar findings were presented by Rouquette et al. who showed overall success
rates of 91.7 %, complication rates of 8.4 %, and recurrence in 12.5 % of patients
[27].
The Stag Beetle knife Junior (SB knife Jr., Sumitomo Bakelite Co., Tokyo, Japan) is
a scissor-shaped cutting tool that can be used to divide the septum and is often used
with a diverticuloscope or cap. Both blades of the SB knife Jr. are insulated externally.
It has two practical advantages over other cutting devices. First, the SB knife Jr.
allows an incision from the apex to the base of the septum but with a scissor-like
movement, which pulls the muscle fibers towards the endoscope while cutting. In addition,
the 360° rotational ability increases therapeutic precision and prevents unwanted
deep incisions that may lead to perforation. In a retrospective study of 31 patients
undergoing SB knife septal myotomy, Battaglia et al. described a median procedure
time of only 14 minutes, with 83.9 % of patients in remission from symptoms after
a median follow-up of 7 months [28]. The efficacy and safety data were replicated in 52 patients by Goelder et al.,
who reported a low recurrence rate of 9.6 % over 6 months, without the occurrence
of perforation or mediastinitis [29].
The settings for the electrosurgical generators vary between the different brands
and models and can be different for different devices. Therefore, specific settings
for the electrosurgical generator being used should be requested from the manufacturer.
3.3.9 Post-procedural care
No specific recommendations regarding the postoperative care of patients can be deduced
from the analysis of the current literature. However, after the procedure, patients
should be carefully monitored to recognize possible complications. Patients are routinely
kept nil per os for 24 hours. In many published series, patients were allowed liquid
diet the next day if their course was unremarkable. There is no evidence to support
a contrast study being a prerequisite to resume oral intake unless a perforation is
suspected.
4 Gastroesophageal reflux disease
4 Gastroesophageal reflux disease
GERD is a common condition that affects approximately 8.8 % – 25.9 % of European adults
[30]. Medical therapy using proton pump inhibitors (PPIs) and surgical treatment by means
of fundoplication are both proven to be effective. Some patients are either reluctant
to use chronic medication or are allergic to PPIs, but do not want to undergo a surgical
solution. In addition, chronic PPI use imposes significant costs.
In the past, several endoscopic treatment modalities have been evaluated, but most
of these were finally withdrawn from the market owing to lack of efficacy or major
side effects [31]
[32]
[33]
[34]
[35]
[36]
[37]. Nowadays, several new endoscopic modalities are on the market or are being evaluated.
4.1 Transoral incisionless fundoplication (TIF)
ESGE recommends against the widespread clinical use of transoral incisionless fundoplication
(TIF) as an alternative to PPI therapy or antireflux surgery in the treatment of GERD,
because of the lack of data on the long-term outcomes, the inferiority of TIF to fundoplication,
and its modest efficacy in only highly selected patients. TIF may have a role for
patients with mild GERD who are not willing to take PPIs or undergo antireflux surgery.
Strong recommendation, moderate quality of evidence, level of agreement 92.8 %.
Transoral incisionless fundoplication (TIF) is performed with an endoscopic suturing
device using T-fasteners and aims to create a gastroplication that reinforces the
antireflux barrier. TIF has been evaluated in five randomized controlled trials (RCTs)
in patients mostly with moderate GERD, excluding those with large hiatal hernias (> 2 cm),
Los Angeles grade C or D esophagitis, or Barrett’s esophagus [38]
[39]
[40]
[41]
[42]. TIF was evaluated after 6 months of follow-up and compared with a sham procedure
[42], a sham procedure and PPI therapy [41], or in an unblinded manner with PPI therapy [38]
[39]
[40]. A meta-analysis showed that a clinical response, defined by an improvement of at
least 50 % in the GERD health-related quality of life (GERD-HRQL) scores or remission
of heartburn and regurgitation, was observed in 66 % of patients treated with TIF
and 30 % of the control groups [43]. Objective measurement of reflux showed a limited decrease in esophageal acid exposure
in patients treated with TIF, a similar level of decrease to that observed in patients
taking PPIs.
No long-term data are available from RCTs, but results from uncontrolled studies show
decreased effectiveness over time, with PPI cessation rates ranging from 70 % at 6
months to 34 % at 5 years, which suggests the procedure has a short-term benefit in
two-thirds of patients. Severe adverse events, including esophageal perforation and
bleeding, have been reported in 2.4 % of patients [43]. TIF was also compared to Nissen fundoplication in a prospective open study [44]. Objective and symptomatic evaluation of reflux showed superiority of the surgical
fundoplication.
To conclude, TIF may improve GERD symptoms in the short term, but long-term control
of reflux is not achieved in the majority of patients with well-characterized and
uncomplicated GERD. The exact positioning of TIF in the armamentarium remains unclear:
it might offer some symptomatic relief for patients who are intolerant to PPIs, not
willing to take PPIs, or for those who have persistent regurgitation on PPIs but are
reluctant to undergo antireflux surgery.
4.2 Medigus ultrasonic surgical endostapler (MUSE)
ESGE recommends against the use of the Medigus ultrasonic surgical endostapler (MUSE)
in clinical practice because of insufficient data showing its effectiveness and safety
in patients with GERD. MUSE should be used in clinical trials only.
Strong recommendation, low quality evidence, level of agreement 100 %.
The Medigus ultrasonic surgical endostapler (MUSE; Medigus, Omer, Israel) is a system
that integrates flexible video-endoscopy with an ultrasonic range finder and a surgical
stapler. At the center of the endoscope is a rigid section of approximately 66 mm
that holds a cartridge containing five 4.8-mm standard “B”-shaped titanium surgical
staples. The tip of the endoscope contains an anvil for the staples as well as two
small screws. An ultrasonic range finder measures the distance between an ultrasonic
mirror in the cartridge and the tip of the endoscope.
Currently, the MUSE device has been evaluated in a prospective multicenter trial including
66 patients with a short-term follow-up period [45]. After 6 months, the GERD-HRQL score improved by more than 50 % while off PPI therapy
in 73 % of patients (95 % confidence interval [CI] 60 % – 83 %) and 42 patients (64.6 %)
were no longer using daily PPI medication. Two patients suffered from severe complications
(empyema in one, hemorrhage in the other). The 4-year follow-up data were reported
in 37 of the initial 66 patients [46]. Both the GERD-HRQL and percentage of patients off PPIs had decreased slightly but
significantly over time; however, they remained significantly better than at baseline.
Danalioglu et al. compared the results of the MUSE in 11 patients with laparoscopic
fundoplication in 16 patients [47]. Patients however were not randomized, and a hiatal hernia of > 3 cm was an exclusion
criterion for MUSE only. In this small retrospective study, laparoscopic fundoplication
appeared to be more effective after a 6-month follow-up period, and one severe complication
(esophageal perforation) was seen in the MUSE group.
Overall, data on the safety and efficacy of MUSE in the treatment of GERD are scarce
and sham-controlled trials are lacking, as are studies randomizing patients between
MUSE and laparoscopic fundoplication. ESGE therefore recommends against the use of
MUSE outside of the context of clinical trials.
4.3 Radiofrequency energy application to the LES (Stretta)
ESGE suggests that Stretta can be considered in selective patients only, for the sake
of symptom relief and in the absence of erosive esophagitis and a hiatal hernia.
Weak recommendation, moderate level of evidence, level of agreement 92.9 %.
Radiofrequency energy application to the LES (Stretta; Restech, Houston, Texas, USA)
is an endoscopically-guided method in which radiofrequency current is conducted by
a series of radially arranged needles positioned over the esophagogastric junction
(EGJ). Although the exact mechanism by which Stretta opposes further gastroesophageal
reflux is still unclear, the technique is supposed to induce inflammatory changes
that result in submucosal fibrosis, with a subsequent increase in LES pressure and/or
decrease in LES compliance. Stretta is not recommended in patients with erosive esophagitis
or hiatal hernia. It should be noted that Stretta is not available in some countries.
To date there have been four RCTs, 23 cohort studies, and two systematic reviews (one
of which was a meta-analysis). The four RCTs included three that compared Stretta
with sham therapy [48]
[49]
[50], and one that compared Stretta with PPI use [51]. Overall, the quality of evidence from the RCTs on the efficacy of the Stretta procedure
is low, especially as the most important objective outcome parameters, such as acid
exposure time, have often been omitted. No convincing evidence has been provided that
Stretta normalizes acid exposure or LES pressure, but results from these RCTs converge
to show some significant improvement in symptom burden and quality of life in the
short term, although longer term data are still lacking.
The meta-analysis performed by Fass et al. included both RCTs and cohort studies [52]. They concluded that Stretta is efficacious in improving both objective and subjective
clinical end points, except basal LES pressure. Lipka et al. published a systematic
review that was limited to the four RCTs [53]. The pooled results showed no difference between Stretta and sham or management
with PPIs in patients with GERD for the outcomes of mean percentage time the pH was
less than 4 over a 24-hour time course, LES pressure, ability to stop PPIs, or health-related
quality of life.
In terms of the comparison of Stretta vs. fundoplication, two non-randomized prospective
comparative studies have been published, but the methodology of these studies was
flawed (with selection criteria differing in the two groups) and the definitions of
end points and symptom measurements were heterogeneous [54]
[55]. However, some improvement in symptom scores was observed in both studies, while
another prospective study of Stretta as rescue therapy after failed laparoscopic fundoplication
also proved useful in a subset of patients [56].
4.4 Antireflux mucosectomy (ARMS)
In antireflux mucosectomy (ARMS), an endoscopic mucosal resection (EMR) is performed
at the level of the cardia over 180 – 270° degrees of the circumference. The concept
behind ARMS is based on observations of the scars that result after ESD or EMR of
gastric lesions. In this case, the scarring resulting from the healing of the mucosal
resection at the level of the cardia leads to a narrowing of the EGJ and changes the
angle of His, thereby potentially reducing gastroesophageal reflux.
ESGE recommends against the use of antireflux mucosectomy (ARMS) in routine clinical
practice in the treatment of GERD because of the lack of data and its potential complications.
Strong recommendation, low quality evidence, level of agreement 100 %.
Only three case series (single-arm interventional studies) have been reported including
in total 39 PPI-refractory GERD patients without a sliding hernia or with a hernia
no bigger than 2 cm [57]
[58]
[59]. A clinical response was achieved in 69 % – 80 % of patients, with dysphagia occurring
in 13 %. Patient numbers are too small to draw any conclusions on safety and efficacy,
and controlled data are lacking.
5 Intractable constipation
5 Intractable constipation
Constipation is a common clinical condition. It is generally treated with dietary
measures, lifestyle modifications, (osmotic) laxatives, or a combination thereof.
In patients with intractable symptoms, retrograde or antegrade lavage can be considered.
Percutaneous endoscopic cecostomy tube placement describes a technique of placing
tubes in the colon. The general technique is comparable to percutaneous endoscopic
gastrostomy tube placement; however, as the tube is placed directly into the colon,
the risk of complications is generally higher and a significant mortality is noted.
The most common indication for percutaneous endoscopic cecostomy tube placement is
relief of colonic obstruction or antegrade irrigation for colonic motility disorders
[60]. In general, studies on percutaneous endoscopic cecostomy are rare and data collection
is retrospective.
Therefore, the aim within this ESGE guideline is for the first time to provide guidance
on the technique and management of percutaneous endoscopic cecostomy tube placement.
5.1 Indications for percutaneous endoscopic cecostomy
ESGE recommends endoscopic cecostomy only after conservative management with medical
therapies or retrograde lavage has failed.
Strong recommendation, low quality evidence, level of agreement 93.3 %.
To date, no specific literature is available regarding the comparative efficacy of
medical therapy, retrograde lavage, and endoscopic cecostomy in the treatment of constipation.
In general, endoscopic cecostomy is a high risk procedure with significant morbidity
and even mortality and is therefore only applied for intractable cases [60]
[61]
[62]
[63]. Accordingly, conservative approaches should be extensively used before the indication
for endoscopic cecostomy is met.
5.2 Periprocedural management of endoscopic cecostomy
The procedure should be performed with CO2 insufflation with the patient in the left lateral or supine position. The puncture
should be performed under aseptic conditions.
5.2.1 Bowel preparation
There are no studies regarding bowel preparation for patients in whom endoscopic cecostomy
is performed. Rigorous bowel preparation is, however, mandatory as abundant fecal
remnants might increase the risk of septic complications, and severe constipation
is the dominant symptom in these patients. A regimen of 7 days of fiber-free diet
and 3 days of polyethylene glycol (PEG) solution prior to percutaneous endoscopic
cecostomy is adopted by some expert centers.
5.2.2 Use of prophylactic antibiotics
ESGE recommends antibiotic prophylaxis starting before and continuing for 3 days after
the procedure.
Strong recommendation, very low quality evidence, level of agreement 93.3 %.
No study has yet addressed the need for antibiotic prophylaxis for cecostomy. However,
in view of the potential fecal contamination, antibiotic therapy is generally used
in practice [61]
[64]
[65]
[66]. Moreover, patients requiring an endoscopic cecostomy might be critically ill. Antibiotic
prophylaxis should follow local protocols, but could consist of amoxicillin – clavulanic
acid (1 g) or ofloxacin + metronidazole (500 mg) 1 hour before the procedure, with
this mostly being maintained until 72 hours after cecostomy.
5.3 Techniques for endoscopic cecostomy
ESGE recommends fixing the cecum to the abdominal wall at three points (using T-anchors,
a double-needle suturing device, or laparoscopic fixation) to prevent leaks and infectious
adverse events, whatever percutaneous endoscopic cecostomy method is used.
Strong recommendation, very low quality evidence, level of agreement 86.7 %.
Three main techniques of percutaneous endoscopic cecostomy have been used in clinical
practice [61]
[63]
[66]
[67]
[68]
[69]: the pull-through method, the “introducer” method, and laparoscopically assisted
percutaneous endoscopic cecostomy (LAPEC). The limited data do not provide evidence
as to which method should be preferred. As cecostomy is accompanied by a relatively
high frequency of adverse events, which may be serious (especially if no fixation
of the cecum is used), the procedure should be reserved for patients with otherwise
intractable constipation without any other therapeutic option. The necessary steps
for percutaneous endoscopic cecostomy include: good bowel cleansing, use of sedation,
disinfection of the abdominal wall, transillumination, and fixation of the cecum to
the abdominal wall. In procedures where metal anchors are used, these should be removed
within 3 – 4 weeks of percutaneous endoscopic cecostomy tube placement.
5.3.1 Pull-through method
For the pull-through method [63]
[69], a colonoscopy is first performed to identify a site for insertion. The point of
maximal transillumination is infiltrated with local anesthetic and the cecum is fixed
at three points under endoscopic control. An 18 G Seldinger needle (in children, 12 G)
is then passed through the abdominal wall at the center of the sutured triangle and
a guidewire is passed through the needle and grasped by a snare. The guidewire is
withdrawn from the anus and a tube (14 – 20 Fr in adults; 12 Fr in children) is attached
to it and pulled through the abdominal wall. The final position of the internal bolster
is checked endoscopically and the tube is attached to the abdominal wall by an external
bolster.
5.3.2 Introducer method
For the introducer method [61]
[66], after a site for puncture and fixation of the cecum has been identified, a small
incision or a puncture is made and, using a Seldinger technique, an introducer is
advanced into the cecum, before a definitive catheter is placed and fixed. Chait Trapdoor
percutaneous cecostomy catheters (“multiple pigtails”) or balloon catheters (11 – 15 Fr)
are the most frequently used with this technique. Chait Trapdoor cecostomy catheters
may have several advantages: no balloon rupture (and subsequent leak) can occur, no
buried bumper syndrome can occur, granulation tissue overgrowth occurs less frequently,
and these catheters are easily exchangeable.
5.3.3 Laparoscopically assisted percutaneous endoscopic cecostomy (LAPEC)
For LAPEC [67]
[68], a colonoscopy is first performed to identify the cecum. Fixation is then performed
laparoscopically or under laparoscopic control. A cecostomy tube is placed laparoscopically.
Although the procedure can be performed with a single laparoscopic port for the camera,
several centers add two extra ports to allow the cecum to be held to facilitate needle
insertion and for suturing of the cecum to the abdominal wall.
5.4 Choice of technique for endoscopic cecostomy
ESGE suggests the endoscopic route in critically ill patients in whom cecostomy is
considered.
ESGE suggests laparoscopically assisted percutaneous endoscopic cecostomy (LAPEC)
as the preferred technique for patients whose clinical condition is good.
Weak recommendation, very low quality evidence, level of agreement 86.7 %.
A direct comparison between purely endoscopic cecostomy and LAPEC is not available
from the literature. The technical success rates of purely endoscopic cecostomy are
greater than 80 %; complications occur in 30 % – 40 % of patients, and quality of
life improves in general for most patients, although acceptance is reduced in about
25 % of patients, mostly because of pain [61]
[62]
[63]
[64]
[70]
[71]
[72]
[73]
[74]
[75]. While most complications are minor, deaths have been reported secondary to endoscopic
cecostomy-induced (fecal) peritonitis. LAPEC shows a success rate of 95 %, which is
higher than the technical success rate reported for endoscopic cecostomy [67]. In critically ill patients, however, the endoscopic route might be preferred in
order to avoid surgery and extensive sedation.
5.5 Colostomy at other locations
ESGE recommends performing endoscopic colostomy at no locations other than the cecum
unless this is technically not feasible.
Strong recommendation, very low quality evidence, level of agreement 93.3 %.
Although data show the feasibility of performing colostomy at locations other than
the cecum (left colon – descending or sigmoid) for patients suffering from constipation,
there are no data demonstrating any advantage of this approach [69]
[74]
[76]
[77]. Importantly, in some studies, there was a very high and unacceptable incidence
of serious adverse events [69]
[74]. In one retrospective study, analyzing 31 patients who underwent endoscopic colostomy
on the left side of the colon, recurrent complications and infection caused significant
morbidity and necessitated percutaneous endoscopic colostomy tube removal in most
patients (13 of the 14 patients with constipation had to have the tube removed). Moreover,
two patients died because of fecal peritonitis [74].
6 Ogilvie’s syndrome
Ogilvie's syndrome, also known as acute colonic pseudo-obstruction, refers to pathologic
dilatation of the colon without underlying mechanical obstruction [78]. It occurs primarily in patients with serious comorbidities.
In patients with signs or symptoms of acute colonic dilatation, the presence of mechanical
large-bowel obstruction should be excluded with an abdominal computed tomography (CT)
scan or water-soluble contrast enema. Furthermore, routine blood testing, including
complete blood count, serum electrolytes, renal function assessment, and thyroid function,
should be performed during the initial evaluation to check for predisposing and potentially
correctable factors (i. e. electrolyte imbalance, renal insufficiency, infection,
and hypothyroidism).
6.1 Indications for endoscopic treatment
6.1.1 Endoscopic decompression vs. neostigmine
ESGE recommends considering endoscopic decompression of the colon in patients with
Ogilvie’s syndrome that is not improving with conservative treatment.
Strong recommendation, low quality evidence, level of agreement 93.8 %.
Conservative therapy is the initial step in the management of patients with Ogilvie’s
syndrome. In the current literature, the following actions have been described: discontinuation
of narcotics, anticholinergics, and calcium-channel antagonists; correction of electrolyte
abnormalities; nil per os; decompressing the GI tract by nasogastric tube and/or rectal
tube insertion, and frequent position changes [79]. Because these recommendations have never been studied as a single intervention,
their effects are unknown.
In patients with Ogilvie’s syndrome that is not improving with conservative treatment,
both endoscopic decompression therapy and medical therapy with intravenous neostigmine
are considered valid treatment options. The efficacy of endoscopic decompression was
investigated in several retrospective studies, in which the overall success rates
varied between 36 % and 88 % [79]
[80]
[81].
In a recent study, Peker et al. demonstrated that, compared with neostigmine, endoscopic
decompression was more effective as an initial therapy and was more effective at avoiding
a second treatment modality (total response 82 % vs. 49 %, P < 0.001) [80]. Comparable results were shown in the study of Tsirline et al. in which colonoscopy
was significantly more successful than single or repeated neostigmine administration
(no further therapy after one or two interventions: 75.0 % vs. 35.5 %, P < 0.001; and 84.6 % vs. 55.6 %, P = 0.003, respectively) [81]. However, in these two retrospective studies, the efficacy of neostigmine treatment
was much lower compared with previous studies, in which the efficacy of neostigmine
ranged between 61 % and 100 % [79]
[82]
[83]
[84].
Regarding safety, the risk of perforation due to endoscopic decompression is described
in 0 – 5 % of patients [79]. However, perforations are also described in patients with Ogilvie’s syndrome receiving
conservative or neostigmine treatment [81]. Ross et al. demonstrated that patients who fail on medical management and require
interventional procedures, including endoscopic decompression, experience increasing
morbidity and mortality with increasing invasiveness of the procedure, likely reflecting
the severity of their conditions [85].
Because no prospective head-to-head comparisons between endoscopic decompression and
neostigmine treatment are available, no recommendation can be made for the superiority
of one of these two treatment strategies in patients with Ogilvie’s syndrome that
is not improving with conservative treatment. Furthermore, there is a large heterogeneity
regarding the patient population, definition of success, and treatment protocols,
which makes a good comparison between studies difficult. The choice of treatment should
also depend on local expertise and the local situation, for instance the access to
urgent colonoscopy.
6.1.2 Criteria for prompt endoscopic decompression
ESGE recommends prompt endoscopic decompression if the cecal diameter is > 12 cm and
if the Ogilvie’s syndrome exists for a duration longer than 4 – 6 days.
Strong recommendation, low quality evidence, level of agreement 87.5 %.
The relationships between cecal diameter and duration of distension in patients with
Ogilvie’s syndrome and risk of perforation and ischemia were investigated in two retrospective
studies. In one study, the risk of perforation and/or ischemia was higher with increasing
cecal diameter: < 12 cm, 0 % (n = 44); 12 – 14 cm, 7 % (n = 29); > 14 cm, 23 % (n = 69).
A cecal diameter > 14 cm was associated with a two-fold increase in mortality. In
addition, a delay in decompression was associated with higher mortality: < 4 days,
15 %; 4 – 7 days, 27 %; > 7 days, 73 % [86]. Johnson et al. demonstrated that the risk of perforation was related more to duration
of cecal distension (> 6 days) than to the absolute cecal size [87].
When colonic ischemia and/or perforation occur, patients are no longer considered
eligible for endoscopic management and should be referred for surgery.
6.1.3 Recurrence of Ogilvie’s syndrome
ESGE recommends considering repeated endoscopic decompression for recurrence of Ogilvie’s
syndrome.
Strong recommendation, low quality evidence, level of agreement 92.9 %.
The risk of recurrence of Ogilvie’s syndrome after an initial successful decompression
varies widely in the current literature, ranging from 0 – 38 % in patients previously
treated with neostigmine and 0 – 50 % after endoscopic decompression [88].
Repeated endoscopic decompression for recurrence of Ogilvie’s syndrome may still be
effective. Some studies report similar success rates of a second or third colonic
decompression compared with the initial decompression, although the sample sizes were
small [81]
[89]. Other studies suggest that repeated endoscopic decompression is associated with
lower, but still acceptable, sustained clinical success rates: Geller et al. showed
that clinical success was achieved in a significantly higher percentage of patients
undergoing a single decompression compared with those requiring multiple procedures
(95 % vs. 56 %, P < 0.05) [88]. In the study of Vanek et al., repeat colonoscopic decompression demonstrated an
87 % success rate, comparable with the initial colonoscopies, but a higher recurrence
rate of 40 % vs. 22 % after the initial colonoscopies [86].
As for the initial treatment for Ogilvie’s syndrome that is not responding to conservative
management, no prospective head-to-head comparisons between endoscopic decompression
and neostigmine treatment are available for recurrent Ogilvie’s syndrome, making the
choice of treatment dependent on local expertise and the local situation, such as
the access to urgent colonoscopy.
6.2 Periprocedural management of endoscopic decompression
6.2.1 Use of a decompression tube
ESGE recommends the placement of a decompression tube in the right or transverse colon
after endoscopic decompression as this seems to be associated with lower recurrence
rates.
Strong recommendation, low quality evidence, level of agreement 92.9 %.
Several old retrospective studies investigated the use of decompression tube placement
after endoscopic decompression in patients with Ogilvie’s syndrome. Geller et al.
showed in a study comprising 50 patients that the rate of clinical success, defined
as a sustained decompression, was 80 % in patients with endoscopic decompression tube
placement vs. 25 % without tube placement [88]. Placement of a decompression tube in the right or transverse colon had a similar
effect (90 % vs. 83 %, P > 0.05); however, the success rate was lower after tube placement in the hepatic
flexure (63 %), splenic flexure (75 %), or descending colon (0 %) [88]. These findings are in line with those of smaller studies [90]
[91]
[92].
In conclusion, most data suggest lower recurrence rates in patients with decompression
tube placement after endoscopic decompression. Tube placement in the right or transverse
colon seems to have similar effects. However, these conclusions are based on relatively
old and small retrospective studies and RCTs are missing. There is no information
mentioned in the literature regarding the duration for which the decompression tube
should be kept in place. In clinical practice, however, decompression tubes are kept
in place for 1 – 3 days, and spontaneous expulsion of the tube before the intended
time of removal is not a rare event. Low (intermittent) suction can be applied, and
regular flushing (every 2 – 4 hours) with 20 – 30 mL of normal saline is generally
advised to maintain patency.
6.2.2 Bowel preparation
ESGE recommends against the use of oral bowel preparation solutions prior to colonic
decompression as these may worsen dilatation of the colon.
Strong recommendation, very low quality evidence, level of agreement 93.8 %.
There are no studies regarding bowel preparation in patients with Ogilvie’s syndrome
undergoing endoscopic decompression. However, use of oral bowel preparation solutions
is not recommended prior to colonic decompression as these may worsen dilatation of
the colon in the absence of bowel transit. The usefulness of enemas before endoscopic
decompression has never been investigated and remains unclear.
6.2.3 Post-procedural oral PEG solution
ESGE recommends the administration of oral PEG solution in patients with Ogilvie’s
syndrome after initial resolution of colonic dilatation as it decreases the risk of
recurrence.
Strong recommendation, low level of evidence, level of agreement 100 %.
One small randomized placebo-controlled trial including 30 patients who initially
responded to neostigmine or colonoscopic decompression demonstrated that administration
of oral PEG solution significantly decreases the rate of relapse compared with placebo
(0 % vs. 33 %, P = 0.04) [93]. The prescription of other types of laxatives after successful decompression, especially
those exerting an effect on colonic motility, seems reasonable and rational, but supportive
studies are lacking.
6.3 Role of percutaneous endoscopic colostomy
ESGE recommends considering percutaneous endoscopic colostomy/cecostomy for patients
with Ogilvie’s syndrome that is refractory to pharmacologic and endoscopic treatment,
especially in those not amenable to surgical intervention because of an increased
perioperative risk.
Strong recommendation, very low quality evidence, level of agreement 80.0 %.
Several studies report data regarding percutaneous endoscopic colostomy placement
for various indications; however, the total number of patients with Ogilvie’s syndrome
is relatively low. Baraza et al. performed 35 percutaneous endoscopic colostomies
in 33 patients, of whom four had recurrent Ogilvie’s syndrome and were considered
poor candidates for an operation [69]. Symptoms resolved in 74 % of all patients, including in three of the four patients
with recurrent Ogilvie’s syndrome. Major complications occurred in four patients:
three cases of peritonitis secondary to fecal contamination and one death. In another
small study, eight percutaneous endoscopic cecostomies were performed: six for colonic
pseudo-obstruction and two for chronic constipation [63], with seven of the eight cases successful and resulting in clinical improvement.
One patient required surgical removal of the percutaneous endoscopic cecostomy tube
for fecal spillage resulting in peritonitis. In a retrospective study from Cowlam
et al., an improvement in symptoms was reported in 81 % of 31 patients after a percutaneous
endoscopic colostomy was performed, including in five patients with acute-on-chronic
colonic pseudo-obstruction. One of these five patients died from fecal peritonitis;
in three, the tube was removed because of infection [74]. Similar results were shown in other case reports [71]
[94]
[95].
Percutaneous endoscopic colostomy, although certainly not devoid of complications,
has two potential advantages over surgery in patients with refractory Ogilvie’s syndrome.
Most importantly, general anesthesia can be avoided. Furthermore, tube placement is
reversible after an improvement in symptoms. Therefore, percutaneous endoscopic colostomy
should be considered as an alternative to surgery in patients with Ogilvie’s syndrome
that is refractory to pharmacologic and endoscopic treatment, despite the fact that
there are no comparative data.
Disclaimer
The legal disclaimer for ESGE guidelines [2] applies to this Guideline.
Endoscopic management of gastrointestinal motility disorders – part 2: European Society
of Gastrointestinal Endoscopy (ESGE) Guideline
Weusten BLA.M., Barret M, Bredenoord AJ et al.Endoscopy 2020; 52: 600–614
In the above-mentioned article, the institution of Daniel Pohl has been corrected.
This was corrected in the online version on June 24, 2020.
