Introduction
Through-the-scope (TTS) clips have been introduced successfully into interventional
endoscopic therapy, for example in cases with colonic (mostly iatrogenic) perforations
[1] and colonic bleeding [2]; however, the clinical feasibility of closing perforations has been limited to small
defects of less than 2 cm. Recently, an over-the-scope (OTS) clip was developed primarily
for the closure of endoscopic procedures such as full-thickness resection (EFTR) and
natural orifice transluminal endoscopic surgery (NOTES) [3]. The OTS clip, also termed bear claw clip, is a large endoscopic clipping device
made from nitinol. OTS clips have since also been used in the event of bleeding and
perforations, predominantly in the upper gastrointestinal tract, with higher efficacy
than TTS clips [4]. Data on OTS clip placement in the colon, however, are scarce. Although therapy
has been reported to be very successful overall [5]
[6]
[7]
[8]
[9]
[10]
[11], most series have included only small numbers of patients and were performed in
highly trained centers; thus, data are likely to be biased [12] and may therefore not represent the general effectiveness in clinical reality. Furthermore,
the safety of OTS clip application, especially in the colon, has not been studied
in large cohorts [13].
In the present study, a novel approach was chosen to investigate the safety of OTS
clip placement in the colon. As application of OTS clips generates a specific administrative
code in the German diagnosis-related group (DRG) reimbursement system, patients treated
with OTS clip placement in the colon could be retrieved from a large database of a
health insurance company. This enabled us to generate data representing routine clinical
practice in colonoscopy in terms of indications, effectiveness, and complications
of OTS clip use in the colon. Procedural application of OTS clips is exemplified by
a case with a colonic fistula in [Fig. 1].
Fig. 1 Application of the over-the-scope (OTS) clipping system in the colon. Example of
fistula formation in the transverse colon after complicated gastric resection. a Endoscopic view of the fistula. b Fluoroscopy after administration of contrast agent to the colon, showing the fistula
(arrows). c Endoscopic view after application of an OTS clip. d Confirmation of fistula sealing following administration of contrast medium (the
OTS clip is visible proximal to the endoscope).
Methods
Using a health insurance database of approximately 10 million insured patients, colonoscopy
cases involving application of the OTS clipping system (Ovesco Endoscopy GmbH, Tübingen,
Germany) on the same day between January 2015 and March 2019 were identified. This
database contains all procedures performed in hospitals as well as codes for outpatient
procedures (International Classification of Diseases [ICD] codes–10th revision; German
operation and procedure codes [OPS] equivalent to International Classification of
Procedures in Medicine [ICPM] codes; Einheitlicher Bewertungsmaßstab [EBM]) [14]
[15]. Codes for colonoscopy (OPS codes 16500, 16501, or 16502; EBM 01741, 13421, or 13422)
and the specific OPS code for OTS clips (5469s3), medically documented within the
scope of patient billing, were used for operationalization in the study. Patients
undergoing EFTR were not included in the study as OTS clip use associated with the
EFTR system generates a different OPS code. However, the code for OTS clip use does
not differentiate between clipping in the small bowel and colon; therefore, all patients
who underwent an upper GI endoscopy on the same day of clipping were excluded from
the analysis.
Using additional codes during the hospital stay (ICD and OPS), the presumed indication
for OTS clipping was identified. Details for group allocation are shown in Table 1s in the online-only supplementary material. Accordingly, the following groups were
formed by a stepwise analysis ([Fig. 2]): Group A, OTS clip closure of iatrogenic perforations occurring during colonoscopy
based on ICD codes for wall injuries or peritonitis; Group B, OTS clip application
in the context of polypectomy, also based upon respective OPS codes; Group C, colonic
bleeding identified by specific ICD codes of colonic bleeding, acute anemia, and/or
OPS codes for transfusion requirements. Group D included a large variety of indications
for use of OTS clips (e. g. fistulas, anastomotic leaks). Group D also included clip
application at various times during an often prolonged hospital stay, and with very
few endoscopic and/or surgical interventions occurring within the 10-day observation
period; therefore, this group was omitted from further analysis.
Fig. 2 Analysis of data after over-the-scope clip application. OTS, over-the-scope; GI,
gastrointestinal; ICD, International Classification of Diseases; OPS, operation and
procedure codes; EBM, Einheitlicher Bewertungsmaßstab.
If cases presented with codes potentially allocating patients to more than one group,
we used a predefined hierarchy ([Fig. 2]). Perforation was always placed in the primary position; for example, if a polypectomy
led to perforation (and the perforation was coded), this patient would be assigned
to group A “perforation”. Bleeding due to polyp removal would primarily be assigned
to “polypectomy” (Group B), not to “bleeding” (Group C). Consequently, therapeutic
application of an OTS clip (e. g. due to perforation and/or bleeding) could only be
identified if these events were documented by the specific codes.
The date of OTS clip application is exactly documented in claims data during the course
of the hospital stay. Therefore, it is possible to track precisely further interventions
occurring during follow-up. The search for such events was carried out along a list
of predefined specific codes (OPS and EBM codes; Table 2s) to identify surgical procedures as well as colonoscopic reinterventions during follow-up. If
any of these codes showed up during the computer-assisted search for events, every
individual case was subsequently analyzed by a clinician experienced in both gastroenterology
and endoscopy as well as in coding. This approach was necessary for the reconstruction
of the individual clinical course, as the analysis of additional OPS and EBM codes
alone did not, per se, give a clear picture of what had been happening to the patient
during follow-up. Thus, information on the type of operative procedure and/or additional
colonoscopic interventions (e. g. hemostatic techniques, additional polypectomy) that
had been performed could be retrieved from the database. As data were available on
the preceding medical records in each individual case, it was possible to differentiate
between new diagnoses and pre-existing disease (e. g. in the case of colorectal cancer
[CRC]). Finally, the results from individual evaluations were once again verified
using computer-assisted tools.
In order to characterize the multimorbidity of patients, the Elixhauser score, a modification
of the Charlson comorbidity index suitable for analyses with administrative data,
was calculated for each patient. The Elixhauser score is a validated comorbidity measure,
based on 30 selected ICD codes of comorbid diseases (e. g. heart diseases, diabetes,
stroke) [16]
[17].
Results
During the study period, 833 patients underwent colonoscopy with simultaneous OTS
clip application. A total of 328 patients also underwent upper GI endoscopy on the
same day, and these cases were excluded from further analysis, leaving 505 patients
with an OTS clip solely in the colon for further evaluation ([Fig. 2]). OTS clips were used with increasing frequency between 2015 and 2018, both in terms
of the number of patients treated and the number of hospitals employing the OTS clipping
system ([Fig. 3]). Overall, the OTS clipping system was applied in 212 different hospitals with a
wide range: clips were used only once during the study period in 120 hospitals, whereas
one hospital employed OTS clips in 30 patients. The proportion of patients allocated
to groups A-D (see below) remained relatively stable during this period.
Fig. 3 Use of the over-the-scope (OTS) clipping system between 2015 and 2018. a Number of hospitals using the device. b Number of patients treated by OTS clips, including indications for clip application.
Total number of patients per year is shown above each column. Group A = perforations;
Group B = polypectomy; Group C = bleeding; Group D = others (e. g. fistulas, anastomotic
leaks).
Demographic details of patients are shown in [Table 1]. In patients with colonic bleeding (Group C), there was a tendency toward more comorbidities
compared with patients in the polypectomy group (Group B), as shown by a higher Elixhauser
score, whereas the Elixhauser score was not different between Groups A and B.
Table 1
Demographic data of patients (n = 505).
|
Parameter
|
Group A (Perforation)
|
Group B (Polypectomy)
|
Group C (Bleeding)
|
Group D (Other)
|
|
Patients, n (%)
|
80 (15.8)
|
315 (62.4)
|
51 (10.1)
|
59 (11.7)
|
|
Age, mean, years
|
64
|
67
|
71
|
63
|
|
Males, %
|
51
|
62
|
67
|
61
|
|
Parallel coding of polypectomy, n (%)
|
35 (43.8)
|
NA
|
NA
|
ND
|
|
Parallel coding of bleeding, n (%)
|
39 (48.8)
|
85 (27.0)
|
NA
|
ND
|
|
Elixhauser score (95 %CI)
|
7.0 (4.8–9.1)
|
6.1 (5.1–7.0)
|
9.6 (6.8–12.3)
|
8.4 (5.9–10.8)
|
|
Death ≤ 10 days, n (%)
|
1 (1.3)
|
0
|
1 (2.0)
|
0
|
|
Surgery ≤ 10 days, n (%)
|
11 (13.8)
|
5 (1.6)
|
4 (7.8)
|
0
|
|
Repeat colonoscopy ≤ 10 days, n (%)
|
5 (6.3)
|
17 (5.4)
|
6 (11.8)
|
1 (1.7)
|
NA, not applicable; ND, not determined.
Group A: perforations
OTS clips were applied in 80 patients for attempted closure of iatrogenic perforations
that occurred during colonoscopy, 43.8 % and 48.8 % of which were also associated
with polypectomy and bleeding, respectively. In 11 patients (13.8 %), coding included
perforation, polypectomy, and bleeding.
In patients treated with an OTS clip for documented perforation, 11 patients (13.8 %)
underwent an operative procedure during the short follow-up period of 10 days after
clipping. In nine of these cases, surgery was carried out within approximately 24
hours after clipping. In eight patients, laparoscopic suturing of the defect was the
only operative procedure, whereas in three patients (one of them with CRC) surgery
included resection ([Table 2]). Laparoscopic suturing might have been performed prophylactically or due to insufficient
closure of the leak. Two patients underwent resection of the right-sided colon within
24 hours without evidence of CRC, and these cases probably represent early definitive
treatment failure of leak closure by OTS clip placement.
Table 2
Surgical interventions within 10 days after application of over-the-scope clips.
|
Surgical intervention
|
Group A (Perforation)
(n = 11)
|
Group B (Polypectomy)
(n = 5)
|
Group C (Bleeding)
(n = 4)
|
|
Laparoscopy only
|
0
|
1
|
0
|
|
Laparoscopic suturing
|
8
|
1
|
0
|
|
|
1
|
0
|
–
|
|
Resection
|
3
|
3
|
3
|
|
|
1
|
3
|
2
|
|
Surgery unrelated to indication for OTS clips
|
0
|
0
|
1
|
CRC, colorectal cancer; OTS, over the scope.
Additional endoscopic procedures beyond the index colonoscopy and clipping ([Table 3]) were carried out in five patients within the 10-day interval but colonoscopy did
not include any further intervention in any of these patients. One death occurred
in this group 1 day after OTS clipping in an 89-year-old man with severe concomitant
cardiac diseases.
Table 3
Colonoscopic reinterventions within 10 days after application of an over-the-scope
clip.
|
Endoscopic intervention
|
Group A (Perforation)
(n = 5)
|
Group B (Polypectomy)
(n = 17)
|
Group C (Bleeding)
(n = 6)
|
|
Colonoscopy only
|
5
|
6
|
1
|
|
Colonoscopy + additional polypectomy
|
0
|
3
|
0
|
|
Colonoscopy + clip/injection/thermal/hemostatic agents
|
0
|
6
|
3
|
|
Colonoscopy + new OTS clip
|
0
|
2
|
2
|
|
After removal of first OTS clip
|
–
|
1
|
0
|
OTS, over-the-scope.
Group B: polypectomy
The predominant indication for OTS clip application occurred in the context of polypectomy
(n = 315), with 27.0 % of clip placements being associated with bleeding. In the remaining
patients, it was not possible to confirm whether OTS clips were applied prophylactically
or for treatment of complications (e. g. perforation and/or bleeding) because specific
codes were missing from the database. Early colonic surgery within 10 days after clipping
was necessary in five patients ([Table 2]). Surgical interventions included resection in three cases (all of which had CRC),
laparoscopic suturing in one case, and laparoscopy without any further procedure in
one patient.
Endoscopic reinterventions early after OTS clip placement were performed in 17 patients
(5.4 %) and included a variety of additional interventions targeted to hemostasis,
additional polypectomy, or (presumed) inspection of the polypectomy site ([Table 3]). No death occurred in this group during the 10-day follow-up.
Group C: bleeding
Colonic bleeding was another common indication for OTS clip application in the colon
(n = 51) in addition to bleeding events in groups A and B. One patient probably with
an ongoing diverticular bleed (as exemplified by prior repeat attempts to stop bleeding
endoscopically) underwent resection of the sigmoid colon 8 days after OTS clip application,
whereas in two cases, resection was associated with CRC.
Repeat colonoscopy was performed in six patients early after OTS clip application;
in five of these cases, repeat interventions were again probably aimed at controlling
bleeding as exemplified by interventions using TTS clips, injections, and even a second
OTS clip in two cases. The estimated overall rebleeding rate (as identified by repeat
endoscopic intervention or surgery during follow-up, excluding cases with CRC) within
10 days after OTS clipping was 10.2 %. One death occurred in an 88-year-old woman
with CRC and severe heart failure 3 days after OTS clip placement.
Safety
In order to capture all delayed complications beyond the 10-day period, surgical procedures
were analyzed in groups A, B, and C up to 30 days after OTS clip placement. As shown
in [Table 4], 17 patients underwent surgery 11–30 days after OTS clip placement (mean 20 days).
Surgery was associated with CRC (n = 11) and colon adenoma (n = 1). In four patients,
resection was carried out most likely for persistent or recurrent bleeding, as revealed
by preceding endoscopic interventions using hemostatic tools. In one Group A patient,
a plausible cause for surgery could not be identified and might represent delayed
failure of the OTS clip to permanently close the perforation.
Table 4
Surgical interventions between days 11 and 30 after application of over-the-scope
clips.
|
Surgical intervention and indication
|
Group A (Perforation)
(n = 6)
|
Group B (Polypectomy)
(n = 8)
|
Group C (Bleeding)
(n = 3)
|
|
Resection
|
5
|
8
|
2
|
|
Resection with stoma
|
1
|
–
|
1
|
|
Cause for surgery
|
|
|
3
|
6
|
2
|
|
|
–
|
1
|
–
|
|
|
2
|
1
|
1
|
|
|
1
|
–
|
–
|
CRC, colorectal cancer.
Discussion
Indication, effectiveness, and safety of OTS clip placement in the colon is not yet
established. OTS clips were primarily developed for NOTES and were subsequently [18] used for EFTR (not included in this study); however, reports of colonic OTS clip
application describe only small case numbers mainly from highly specialized centers
[5]
[6]
[7]
[8]
[9]
[10]
[11] or may be prone to publication bias [19], and may not reflect routine clinical use. Therefore, the clinical efficacy of OTS
clip placement in the colon still needs further evaluation. As use of OTS clips generates
a specific administrative code in the German DRG system, which is relevant for reimbursement,
analysis of administrative data offers great potential to study the clinical efficacy
of endoscopic innovations in clinical practice. Secondary data from the statutory
health insurance funds may be used for the measurement of outcomes over long periods
of time [14]. Even failures are more likely to be coded, as the specific code leads to substantial
increases in the reimbursement. The database used in the current study derives from
the largest health insurance company in Germany (Techniker Krankenkasse), with about
10 million insured patients. Although not fully representative of all patients in
Germany, results are likely to give a realistic image of the German health system.
Thus, data obtained on the use of the OTS clipping system in this study are very likely
to reflect clinical routine conditions.
In the present study, we identified 505 patients who received an OTS clip in the colon.
The OTS clips were not extensively used, and closure of perforations must have been
performed in many instances without extensive experience in using this clipping system.
Concomitant coding (ICD-10, OPS [ICPM-like] codes) enabled us to identify the presumed
indication for clip application in a large number of patients.
A total of 80 patients experienced a perforation, either during colonoscopy alone
or in combination with a polypectomy and/or bleeding; these patients were subsequently
treated with an OTS clip in this emergency situation. This is by far the largest reported
cohort of patients with colonic perforations treated with an OTS clip. It is acknowledged
that patients are only suitable for clipping if the perforation is recognized immediately
during the endoscopic procedure, and the OTS clip placement must be technically feasible
too. This cohort admittedly represents a subset of patients with a more favorable
prognosis even if they require surgery [20]. However, the rate of additional surgical interventions after OTS clipping was remarkably
low, occurring in only 11 /80 patients. Furthermore, the majority of patients were
treated solely by laparoscopic suturing, and only three patients required resection
(one case with CRC). It was not possible to evaluate whether laparoscopic suturing
was performed for unsuccessful clipping or in addition to OTS clipping to secure the
closure. Even if all patients who underwent subsequent surgery are regarded as treatment
failures, OTS clip placement presumably replaced surgery in more than 85 % of patients.
The success rate is thus similar to a report by Weiland at al. [19].
Closure of iatrogenic perforations by OTS clip placement requires the same watchful
observation as surgery to ensure that complications are not missed: in principle,
the same delayed complications may occur after application of the OTS clip system
as after surgery, and this may have been the case in two patients in the cohort of
patients in this study. However, even in patients with primary failure of the closure
by clipping, secondary clipping is an option, potentially avoiding surgery. Thus,
the advantage of OTS clipping may evolve as an alternative to surgery, and even in
cases of incomplete closure necessitating surgery, contamination of the peritoneal
cavity and peritonitis may be reduced.
Polypectomy was the dominant indication for use of OTS clips. For methodological reasons,
it was possible to only partially identify the clinical situation that led to clipping.
Bleeding was associated with OTS clipping in 27.0 % of patients. In the remaining
patients, OTS clip application was most likely also performed due to temporary bleeding
and eventually in a few patients with (presumed) perforation during polypectomy; however,
respective coding is lacking. Only five patients required surgery (1.6 %), which was
due to CRC in three patients; the rate of endoscopic reinterventions (5.4 %) was low.
These findings suggest that OTS clipping contributed substantially to a definitive
therapy for polypectomy complications; moreover, it is likely that large polyps were
removed and required OTS clips afterwards as the data were derived from hospitals
only. Recently, TTS clip application following polypectomy has been shown to reduce
the risk of bleeding [21]
[22]; however, the OTS clips are supposed to be even more effective, as demonstrated
in recurrent peptic ulcer bleeding [23]. This hypothesis requires testing in further studies.
Colonic bleeding is an endoscopic challenge, as this condition is associated with
multimorbidity and use of anticoagulants [24]. Therefore, this cohort has a different prognosis from patients with bleeding after
polypectomy. Identification of the exact bleeding source using administrative data
is difficult, as specific ICD codes exist only for selected types of colonic bleeding
(e. g. diverticular bleeding). Though lower gastrointestinal (particularly diverticular)
bleeding stops spontaneously in 80 %–85 % of cases [25], endoscopic efforts to stop an active bleed are frequently unsuccessful in the colon.
Despite progress made by TTS clips, rebleeding remains a problem [26]. Identification of the exact bleeding source is necessary for precise clip placement,
yet often difficult during colonoscopy. A clip that grasps more tissue may therefore
be advantageous [27]. The present study seems to support this hypothesis, as only one patient underwent
surgery (resection of the sigmoid colon) probably due to ineffective hemostasis, whereas
the remaining patients clearly required surgery for bleeding CRC. The estimated rebleeding
rate (excluding cancer patients) of 10 % seems lower compared with 16 % reported in
a recent meta-analysis [28]. Endoscopists should, however, always critically evaluate whether the indication
for an OTS clip is appropriate and should definitively avoid overuse.
There has been some concern about the long-term safety of OTS clips. Complications
reported to date [29]
[30] include those that require surgery not necessarily within 10 days of clip placement.
Therefore, surgical procedures beyond the 10-day interval were also analyzed in the
present study to identify delayed failures and complications that might result from
altered local blood perfusion. However, up to 30 days after OTS clipping, surgery
was performed almost exclusively for underlying diseases (CRC, bleeding, etc.), and
in only one case out of 505 patients may thus be classified as delayed failure. This
matches reports related to OTS clip-related failures and complications; however, watchful
observation is mandatory in patients after OTS clip placement even though it is possible
to replace an existing OTS clip [31], which was also done in the present cohort.
Data for statutory health insurance are primarily collected for billing of medical
benefits and can therefore only be used as secondary data for scientific analyses
in healthcare research. In order to be able to use this huge analytic potential of
claims data on a valid basis, limitations of secondary data must be taken into consideration
[14]
[15]. In particular, some ICD codes lack some degree of diagnostic accuracy; for example,
ICD codes for lower gastrointestinal bleeding may lack precise definitions. Whereas
a time-based assignment is exactly feasible by means of OPS codes, the exact date
of ICD events is not always determinable.
To combine day-based OPS information with period-related ICD diagnoses optimally,
clinical (medical) expertise was systematically interlinked with data analytical competence.
The resultant knowledge enabled a more complex and also a more detailed operationalization.
Subsequently, more precise classification of patients into the different treatment
groups and improved recording of complications could be ensured.
The strengths of this study include the novel approach to evaluating endoscopic innovations
in a large number of patients, substantially exceeding previously reported cohorts
in number. Data were obtained from routine clinical practice with minimal risk of
under-reporting. Study limitations include the fact that the analysis was based on
a registry consisting of administrative data; codes for diagnostic and therapeutic
procedures and diagnoses had to be translated back into the clinical course without
access to clinical reports. Although one of the authors with profound clinical experience
looked at many individual cases (e. g. all patients with repeat endoscopic and/or
surgical interventions), reconstruction of the clinical course could not be achieved
in every single case, though it was probably achieved in the vast majority of patients.
In conclusion, the application of OTS clips in the colon offers a new tool for various
clinical settings. The OTS clipping system as an alternative to surgical procedures
is restricted to use in suitable patients with iatrogenic perforations and may enhance
the prophylactic and therapeutic armamentarium in difficult polypectomies and colonic
bleeding; however, overuse should be strictly avoided.
