Introduction
Peutz – Jeghers syndrome (PJS) is an autosomal dominant syndrome, characterized by
the development of multiple hamartomatous polyps throughout the gastrointestinal tract
[1]
[2]. It has been reported that by the age of 18 years, 70 % of patients with PJS are
at risk of intussusception requiring laparotomy associated with increasing polyp size
[3]. The development of double-balloon endoscopy (DBE) has enabled endoscopic polypectomy
of small-bowel polyps [4]. Repeated polypectomy of small-bowel polyps has been reported to reduce the risk
of intussusception [5]
[6]
[7].
However, there are some concerns regarding snare polypectomy of small-bowel polyps.
In order to achieve an R0 resection, polypectomy with an adequate margin is required.
In difficult circumstances, snare polypectomy takes an extended period of time. Prophylactic
clip application after polypectomy is often performed to reduce delayed bleeding.
Although collection of the resected specimens takes time, the malignant potential
of PJS polyps is very low. Peritoneal adhesions due to previous laparotomies can make
endoscope maneuverability difficult. In some cases, it is impossible to accomplish
polypectomy even if the lesion can be detected.
In order to overcome these problems, we have performed polyp strangulation using endoclips
and/or a detachable snare ([Fig. 1]) [8]
[9]. It was confirmed that most polyps are passed naturally within a few days. We named
this procedure ischemic polypectomy. In our institution, we started using the ischemic
polypectomy method in 2008, and from 2011 almost all patients with PJS were treated
by ischemic polypectomy. In this study, we evaluated whether ischemic polypectomy
of small-bowel polyps in patients with PJS is feasible, as previously reported for
conventional polypectomy [5]
[6]
[7].
Fig. 1 Endoscopic images of the lesion in patient 9. a A 0-Ip lesion 12 mm in diameter was found in the proximal jejunum. b A long clip was applied to the stalk. c The polyp was discolored after clip placement. d The polyp regressed by Day 5 after clip placement.
Methods
The records of 61 consecutive patients with PJS who underwent DBE at Jichi Medical
University Hospital from July 2004 to August 2017 were retrospectively reviewed. Among
these patients, nine who underwent multiple sessions of ischemic polypectomy and had
no other treatment were included in the series. In order to evaluate the effectiveness
of ischemic therapy, we excluded patients who underwent both ischemic polypectomy
and conventional polypectomy. We defined one session as one hospitalization for therapeutic
DBE in which one or more procedures were performed. Written informed consent was obtained
from all patients before the procedure. This study was approved by the Institutional
Review Board.
All patients were admitted before DBE. A combined retrograde and antegrade approach
was performed at the first session for most patients. Bowel preparation included 2 L
of polyethylene glycol electrolyte solution on the day of DBE using the retrograde
approach. Conscious sedation with a combination of intravenous pethidine and midazolam
was used for all patients. A therapeutic-type (EN-580 T or EN-450T5/W with TS-13140;
Fujifilm, Tokyo, Japan) or short-type (EI-580BT or EI-530B or EC-450BI5 with TS-13101;
Fujifilm) double-balloon endoscope with carbon dioxide insufflation, BioShield irrigator
(US endoscopy, Mentor, Ohio, USA), and a 4-mm transparent cap (D-201 – 10704; Olympus,
Tokyo, Japan) fitted to the tip of the endoscope were routinely used.
We defined ischemic polypectomy for PJS as polyp strangulation using endoclips and/or
a detachable snare without using conventional polypectomy methods ([Video 1]). Our first choice was clip strangulation as shown in [Fig. 1], with application of a long-type hemoclip (HX-610 – 090L; Olympus) to the stalk
of the polyp. For polyps with a thick stalk where it is difficult to apply clips,
we used selective ligation with a detachable snare (MAJ-254 or MAJ-340; Olympus).
These techniques restrict blood flow to the polyp, leading to ischemia and shedding
of the polyp. Success of ischemic polypectomy could be recognized by a change in polyp
color, from the typical mucosal color to dark purple ([Fig. 1c]) in a few seconds. In cases where one clip was not sufficient, a crossed-clip strangulation
method was used [8]. When performing antegrade DBE, we tried to keep the examination time within 120
minutes whenever possible to reduce the risk of adverse events.
Video 1 Ischemic polypectomy for small-bowel polyps in a patient with Peutz – Jeghers syndrome
(patient 8).
At the first session, the priority was to use ischemic polypectomy to treat polyps > 15 mm
to prevent intussusception. In patients with multiple large polyps, we repeated the
DBE and treated as many of the polyps as possible during the same session. If all
of the large polyps could not be removed in one session, we scheduled the next session
after a short interval (within 6 months). In that situation, a single approach (antegrade
or retrograde) was sometimes selected depending on the location of the polyps. During
subsequent sessions, all polyps > 5 mm that were amenable to ischemic polypectomy
were treated. The intervals between sessions were determined for each patient, taking
into account the rate of polyp growth.
The following outcomes were recorded: 1) clinical characteristics (age, sex, history
of abdominal surgery); 2) results (number of treated polyps, number of treated polyps > 15 mm,
maximum diameter of treated polyps); 3) adverse events (development of small-bowel
cancer and the need for laparotomy after the start of ischemic polypectomy).
Statistical analysis was performed using EZR (version 1.32; Saitama Medical Center,
Jichi Medical University, Saitama, Japan) [10]. Correlations between sessions for numerical variables were performed using the
Friedman test. Differences were considered statistically significant with a P value of < 0.05.
Results
Patient characteristics
Nine patients (5 male, 4 female) were enrolled in the study. Patient characteristics
are summarized in [Table 1]. The median age of patients was 35 years (range 15 – 62). Eight patients had a history
of previous laparotomy. The indication for most of the abdominal operations was intussusception.
The median observation period between the first and last therapeutic DBEs was 34 months
(range 12 – 66). A total of 67 therapeutic DBEs were performed in these patients during
the study period.
Table 1
Patient characteristics.
|
Patient
|
Age, years
|
Sex
|
Age at first laparotomy, years/ no. of laparotomies
|
Observation period, months
|
Sessions, n
|
No. of DBEs, total/antegrade/retrograde
|
Treated polyps, total/clipping/endoloop
|
Polyps treated at each session, n
|
Polyps > 15 mm treated at each session, n
|
Max. diameter of polyps treated at each session
|
|
1
|
45
|
F
|
24/1
|
66
|
5
|
12/8/4
|
59/54/5
|
29/13/8/4/5
|
15/6/3/0/0
|
40/40/40/10/10
|
|
2
|
34
|
M
|
0/3
|
34
|
3
|
5/3/2
|
6/3/3
|
3/2/1
|
2/1/0
|
35/30/10
|
|
3
|
62
|
M
|
12/4
|
36
|
4
|
8/4/4
|
36/36/0
|
15/12/7/2
|
2/2/1/0
|
15/15/15/10
|
|
4
|
60
|
F
|
20/4
|
39
|
5
|
11/7/4
|
96/84/12
|
46/8/14/12/16
|
21/4/1/1/1
|
25/18/20/15/15
|
|
5
|
15
|
M
|
None
|
24
|
4
|
6/4/2
|
7/0/7
|
1/2/2/2
|
1/2/2/2
|
30/25/25/25
|
|
6
|
45
|
F
|
16/1
|
36
|
3
|
6/4/2
|
17/16/1
|
6/8/3
|
6/1/0
|
30/15/8
|
|
7
|
19
|
M
|
19/1
|
12
|
2
|
4/2/2
|
5/4/1
|
4/1
|
2/0
|
35/8
|
|
8
|
35
|
M
|
15/2
|
12
|
3
|
6/3/3
|
49/42/7
|
20/20/9
|
11/4/4
|
30/30/40
|
|
9
|
26
|
F
|
5/2
|
15
|
3
|
9/6/3
|
67/56/11
|
40/11/16
|
21/6/5
|
50/20/18
|
DBE, double-balloon endoscopy; F, female; M, male.
Ischemic polypectomy
A total of 352 polyps were treated with an ischemic polypectomy, with a median of
36 polyps per patient (range 5 – 96). The median number of treated polyps at each
session was 15 (first session), 8 (second session), 7.5 (third session), 3 (fourth
session), and 10.5 (fifth session), decreasing further, though not significantly,
at subsequent sessions (P = 0.27, Friedman test). The median number of treated polyps > 15 mm per patient showed
a downward trend, decreasing over time (6, 2, 1.5, 0.5, 0.5; P = 0.11). The median maximum size of treated polyps in each patient also showed a
downward trend (30 mm, 20 mm, 19 mm, 12.5 mm, 12.5 mm; P = 0.11) ([Fig. 2]). No patient required laparotomy due to intussusception during the study period.
Fig. 2 The maximum size of polyps treated in each patient during each session: the maximum
size of polyps treated in each patient decreased over subsequent sessions, although
not statistically significantly (P = 0.11, Friedman test).
Adverse events occurred after 1/67 procedures (1.5 %). Mild acute pancreatitis developed
in one patient who had history of four previous abdominal operations and was managed
nonoperatively (patient 3).
Discussion
To the best of our knowledge, this is the first report to introduce ischemic polypectomy,
which we have practiced and used in our institution, as a new therapeutic approach
for small-bowel polyposis in patients with PJS. Routine repeated small-bowel DBE combined
with ischemic polypectomy was feasible for the control of polyps during the follow-up
period, and in particular, decreasing the number of large polyps over time.
A previous DBE-assisted polypectomy study showed that perforation leads to the need
for additional surgery (1.3 %) and that delayed bleeding is the most common adverse
event, although this was infrequent (2.5 %) [7]. Conventional polypectomy using electrocautery may lead to adverse events such as
delayed perforation, delayed bleeding, and post-polypectomy syndrome due to degeneration
of the tissue [11]. Another retrospective report including 13 patients showed no complications associated
with DBE-assisted polypectomy; however, endoscopic resection of some large polyps
was difficult and surgical removal was required [12]. The use of ischemic polypectomy does not lead to tissue damage at the resection
margin. The procedure, especially clip strangulation, is easier to perform than conventional
polypectomy, and is easy to complete even in a limited working space with less than
ideal maneuverability such as in the distal small intestine or the postoperative intestinal
tract ([Fig. 3]). Only the stalk, rather than the entire polyp, needs to be visualized for clip
strangulation. As ischemic polypectomy is easy to perform and many polyps can be treated
in a short time, it may be possible that the number of adverse events is reduced because
of a shorter procedure time. It has been reported that longer procedure times are
associated with a greater incidence of pancreatitis in patients undergoing peroral
DBE [13].
Fig. 3 Endoscopic manipulation in the presence of adhesions, which limit visibility of the
entire polyp. a It is difficult to apply a snare to the stalk of the polyp because of poor endoscope
maneuverability. b Clip strangulation is easy to complete even in a limited working space with less
than ideal maneuverability because only the stalk of the polyp must be seen; visualization
of the entire polyp is not needed.
The main disadvantage of ischemic polypectomy is the uncertainty of the final outcome.
Some polyps could survive and fail to auto-amputate after a single ischemic polypectomy.
We have not performed follow-up DBE to confirm whether all treated polyps underwent
auto-amputation. Even if multiple DBEs are performed in the same session, a large
number of polyps are treated within one DBE, so it is difficult to clearly evaluate
which polyps are lost or survive. Although an absolute number is not available, it
is estimated that 80 % – 90 % of the treated polyps became necrotic. While most polyps
were considered to increase in size over time without treatment, the number of polyps
treated > 15 mm and the maximum diameter of treated polyps tended to decrease over
repeated sessions in this study, which suggests that the ischemic polypectomy was
effective. Ischemic polypectomy can be repeated, which allows any polyps that did
not auto-amputate to be treated at the next DBE session.
This study has some limitations. It was a single-center, retrospective study with
a relatively small number of patients, as PJS is rare. There was a large variation
in the number of polyps among patients, and the intervals between sessions were not
standardized because the intervals were determined according to the needs of treatment.
We conclude that ischemic polypectomy is feasible for the management of PJS polyps.
To confirm the safety and effectiveness of this method, future multicenter, prospective,
randomized studies are needed.
