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Endoscopic full-thickness resection (EFTR) provides complete en-bloc resection with a histopathological evaluation of submucosal, muscular, and serosal layers. The aim of this study was to investigate the efficacy and safety of a novel over-the-scope device for colorectal EFTR.
Material and methods
In this retrospective, observational, open-label case study, a total of 20 patients with superficial colorectal neoplasms, underwent EFTR using a new endoscopic full-thickness resection device (FTRD; Ovesco Endoscopy, Tübingen, Germany). Endoscopic treatment outcomes (technical success, rate of EFTR, adverse events) and early follow-up at three months, were analyzed.
Results
We reported a 100% of technical success, defined as full-thickness resection. Among the R1 resections, histology was negative for neoplasm. Non-lifting adenomas had histology positive for adenocarcinoma: seven T1/G1/sm1; one T1/G1/sm2; one, who underwent a surgical resection, T1/G1/sm3. Mean size of the resected lesions was 26 mm, ranging from 10 to 42 mm. One (5%) patient developed abdominal pain, fever and leukocytosis and was treated conservatively with medical therapy. In all specimens, histological complete resection was confirmed.
Conclusions
EFTR is a feasible and effective technique that could become a valid alternative to EMR and ESD in the management of recurrent adenomas, no-lifting lesions and scars of R1 resections. However, prospective studies are needed to further evaluate the device and technique.
The majority of the superficial neoplasms of the colon can be treated by endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) [
Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the Australian Colonic EMR (ACE) study.
]. However, endoscopic resection of recurrent adenomas, no-lifting lesions (defined as the failure of a lesion to elevate above the surrounding mucosa after submucosal injection underneath the lesion), and T1-carcinomas currently represent a major challenge, at least for Western endoscopists. In the last few years, several studies have been carried out with the aim of creating specific devices for endoscopic full-thickness resection (EFTR) of colorectal lesions [
Colonoscopic full-thickness resection of the colon in a porcine model as a prelude to endoscopic surgery of difficult colon polyps: a novel technique (with videos).
]. The advantage of EFTR is the possibility of obtaining a better histological evaluation with a concomitant closure of the colon wall defect, avoiding abdominal contamination.
A new over-the-scope device, the full thickness resection device (FTRD, Ovesco Endoscopy, Tübingen, Germany), was introduced in 2011 and has been evaluated in several experimental studies [
Aim of our retrospective study was to describe, in a population of consecutive patients with colorectal lesion with no-lifting sign or post endoscopic resection recurrences/residuals, the efficacy and safety of EFTR with FTRD by assessing the completeness of the full-thickness resection in the post-EFTR pathological specimen.
2. Patients and methods
An observational, retrospective, single centre study was conducted to analyse the endoscopic treatment outcomes and early follow-up in consecutive patients who underwent EFTR using the FTRD at a European tertiary referral centre from January to September 2016.
2.1 Inclusion criteria
Inclusion criteria were no-lifting lesions, adenoma recurrence/relapse of previous endoscopic resections with a negative lifting sign, and scars from incomplete endoscopic resection with a positive deep margin (R1 resection).
2.2 Exclusion criteria
Patients <18 years of age, pregnant, without a signed informed consent form, or with coagulopathy (international normalized ratio > 1.5 and/or platelet count <100,000/cu mm), as well as lesions with endoscopic features of deep invasion were excluded from the study.
Written informed consent was obtained from all patients, and the data were treated according to the privacy restriction laws. The study was not funded and was approved by the Ethics Committee of University Campus Bio-Medico (Prot: 49/16 OSS ComEt CBM). Demographics of the study sample, indications and main characteristics of the colonoscopy are shown in Table 1.
Table 1Patient and lesion characteristic, and outcomes following endoscopic full-thickness resection using the FRTD System.
Patient
Age
Sex
Lesion
Diam. (mm)
Location
Hystology prior
Technical success
Hystology
Adverse event
Endoscopic features after EFTR
Resection rate R0
Rate of full-thickness resection
3 months FU
1
66
M
No lift
25
Rectum
ATV-HGD
Yes
T1/G2/sm2
NO
No residual
Yes
Yes
Negative
2
78
F
No lift
35
Distal rectum
NO
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
3
67
M
AR
35
Transverse colon
AT-HGD
Yes
AT-HGD
NO
No residual
Yes
Yes
Negative
4
78
F
R1
20
Recto-sigmoid junction
AT-LGD
Yes
Negative
NO
No residual
Yes
Yes
Negative
5
71
F
AR
25
Distal rectum
ATV-LGD
Yes
ATV-HGD
NO
No residual
Yes
Yes
Negative
6
59
M
No lift
20
Sigmoid
NO
Yes
T1/G1/sm3
NO
No residual
Yes
Yes
Negative
7
64
M
R1
10
Distal rectum
T1
Yes
Negative
NO
No residual
Yes
Yes
Negative
8
72
M
R1
25
Distal rectum
ADK
Yes
Negative
NO
No residual
Yes
Yes
Negative
9
73
M
No lift
35
Ascendent
NO
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
10
79
F
R1
30
Ascendent
ADK
Yes
Negative
NO
No residual
Yes
Yes
Negative
11
78
F
No lift
20
Discendent
NO
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
12
55
M
No lift
25
Distal rectum
ATV-LGD
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
13
55
M
AR
20
Distal rectum
NO
Yes
ATV-HGD
NO
No residual
Yes
Yes
Negative
14
51
M
R1
12
Recto-sigmoid junction
ADK
Yes
Negative
NO
No residual
Yes
Yes
Negative
15
69
M
R1
25
Distal rectum
AT-LGD
Yes
Negative
NO
No residual
Yes
Yes
Negative
16
58
F
R1
42
Caecum
ATV-HGD
Yes
Negative
NO
No residual
Yes
Yes
Negative
17
73
M
No lift
40
Ascendent
ATV-LGD
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
18
74
M
No lift
20
Sigmoid
ATV-LGD
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
19
59
F
No lift
17
Rectum
ATV-LGD
Yes
T1/G1/sm1
NO
No residual
Yes
Yes
Negative
20
65
F
AR
15
Rectum
ATV-LGD
Yes
ATV-HGD
NO
No residual
Yes
Yes
Negative
M, male; F, female; No lift, no lifting lesions; AR, adenoma recurrence/relapse; R1, incomplete resection; ATV-HGD, adenoma tubulo-villosum with high grade dysplasia; AT-LGD, tubular adenoma with low grade dysplasia; ATV-LGD, adenoma tubulo-villosum with low grade dysplasia; T1, the cancer has grown through the muscularis mucosa into the submucosa; ADK, colonic adenocarcinoma
All cases were treated with the FTRD-System (Fig. 1). This tool consists of an over-the-scope (OTSC) system cap with a 14-mm distally-integrated monofilament polypectomy snare. The cap has an inner diameter of 13 mm and a length of 23 mm (measured from the tip of the endoscope). The snare handle runs along the outer surface of the colonoscope, under a plastic sheath that is fixed to the instrument. For the resection, after marking the lesion with either the FTRD marking probe or Argon plasma coagulation (APC), a forceps (FTRD grasper) is used via the operating channel to grasp and traction the lesion inside the cap. Immediately afterwards, the clip is released, and the overlying tissue is removed by the snare (Fig. 2).
Fig. 1The full-thickness resection device (FTRD; Ovesco Endoscopy, Tübingen, Germany): over-the-scope clip is mounted onto a long transparent cap.
Fig. 2FRTD System illustration. A: lesion marked with Argon Plasma Coagulation (APC); B: the target lesion is grasped and pulled into cap with grasping forceps; C: over scope clips is released and tissue snared; D: Inside clip the muscle layer and pericolic flat is clerly visible; E: colonic full-wall resection specimen; F: serosal surface macroscopically visible on the specimen.
Before undergoing an EFTR, patients underwent staging EUS and/or MRI for rectal lesions, as well as abdominal CT scan was performed for lesions localized in other colonic segments.
2.4 Endoscopic outcomes of EFTR
The following outcomes were assessed for the efficacy and safety of the EFTR:
•
Technical success, as en bloc transmural resection;
•
Endoscopic features after EFTR, such as adenomatous residual or free transmural perforations;
•
The resection rate R0, which was defined as the percentage of patients with histologically-negative lateral and deep margins;
•
The rate of full-thickness resection, as confirmed histologically;
•
The adverse events;
These outcomes were evaluated both at the time of the index examination and after 3 months (Early Follow Up).
2.5 EFTR technique
All procedures were performed with CO2 insufflation and under deep sedation (midazolam bolus and continuous propofol infusion). No antibiotic treatment was provided. Each patient first underwent a colonoscopy (CF-Q-180 AL, Olympus Medical System, Tokyo, Japan) in order to identify the lesion and to mark its lateral margins with APC (Erbe APC 300, 25 W). For lesions that were not localized in the rectum, colonoscopy was performed by mounting a cap similar in size to the FTRD cap on the instrument tip (FTRD prOVE CAP, Ovesco Endoscopy, Tübingen, Germany) to evaluate their accessibility. The EFTR was then performed. After the resection, the sample was retrieved, and another colonoscopy without the FTRD system was performed in order to verify the correct positioning of the clip as well as potential complications that may have occurred. All the subjects were hospitalized for two nights and remained fasting after the procedure; their vital parameters and signs of bleeding or perforations were also monitored. Twenty-four hours after the procedure, they followed a semiliquid diet for three days.
2.5.1 Histological evaluation
The resected sample was fixed on a cork, assuring that the cutting edge was fixed directly in contact with the cork surface and was subsequently immersed in 4% buffered formalin. The pathologist systematically evaluated the dimensions of the lesion and the resection margins. The histological classification was carried out according to the Vienna staging system for the epithelial neoplasms of the gastrointestinal tract [
Patients were scheduled for a first follow-up colonoscopy 3 months after the procedure. We performed biopsies of the EFTR scar in each patient, even in the absence of visible adenomatous recurrence (at white light/chromoendoscopy). A post-EFTR surgical treatment was considered in all subjects with “high risk” T1 cancer. T1 colon cancers were defined as “high risk” following the NCCN guidelines: sessile polyps, fragmented specimens, grading 3–4, positive margins, angiolymphatic invasion and depth of submucosal invasion (sm2–3) [
From January 2016 to September 2016, 20 patients underwent EFTR (12 men/8 women; mean age 67, with a range 51–79 years). Indications included scars of incomplete resections (R1 resection) of polypectomies/mucosectomies (7/20), no-lifting lesions (9/20), and adenoma recurrence/relapse (4/20). Ten lesions were localized in the rectum, with one close to the dentate line; five were in the descending colon/sigmoid, one in the transverse colon, three were in the ascending colon, and one was in the caecum (Table 1). Regarding staging pre-EFTR with CT/MRI/EUS, none of the patients had signs of deep local invasion or distant metastasis.
Technical success, which was defined as full-thickness resection, was obtained in all cases and was subsequently histologically confirmed. Among the seven resection scars treated with FTRD, four were localized in the rectum, one was in the ascending colon, and one was in the caecum, with the latter in contiguity to the ileo-caecal valve. All were histologically negative for neoplasia. From a histological point of view, 7/9 of the FTRD-resected lesions without lifting were adenocarcinomas T1/G1/sm1, one was adenocarcinoma T1/G1/sm2; and one was an adenocarcinoma T1/G1/sm3 and eventually underwent a surgical resection.
The mean size of the resected lesions was 26 mm, ranging from 10 to 42 mm. A semiliquid diet was started on the following day in 19 patients. The endoscopic follow-up after 3 months showed spontaneous OTSC dislocation in 100% of the patients, and the scar histology was negative for neoplasia.
3.1 Adverse events
No major immediate or delayed bleeding was observed. There was no perforation or need for emergency surgery. One patient with recurrent adenomas in the distal rectum developed abdominal pain, fever, and leukocytosis after the intervention. This patient underwent a CT scan, which excluded signs of perforation or abscess. The patient was treated conservatively with medical therapy.
4. Discussion
The endoscopic resection of recurrent adenomas with a negative lifting sign, scars of R1 resection and no-lifting lesions is currently a major challenge. Both the presence of fibrosis and localization in the ascending colon are considered independent risk factors for incomplete resection, while the presence of fibrosis associated with a lesion size ≥31 mm is an independent risk factor for perforation [
] showed that the presence of scar/local recurrence is a risk factor for prolongation of the procedure time (OR 4.7, 95% CI 1.7–13.7; p = 0.034) as well as for a fragmented resection (OR 7.8, 95% CI 24–25.0; p = 0.0008). “The ESD”, a time-consuming technique, requires a specific training and high level of skill in order to be safely performed. “The ESD” is currently the endoscopic procedure of choice for the treatment of no-lifting lesions and/or incompletely resected non-lifting adenomas, with a perforation rate of up to 14.7% [
]. It has also been shown that training in highly active centres involving expert tutoring and animal models is remarkably effective at improving the technique and decreasing complications [
]. In recent years, there has been an attempt to produce devices that would enable the EFTR and simultaneously guarantee complete closure of the wall defect. The use of OTSC and its efficacy at closing gastrointestinal perforations and leakages has been widely demonstrated [
]. The technique of using the conventional OTSC to close the wall after a full-thickness resection has been found to be feasible in experimental models. In contrast to closure with the conventional “through-the-scope-clip” or T-tag [
Colonoscopic full-thickness resection of the colon in a porcine model as a prelude to endoscopic surgery of difficult colon polyps: a novel technique (with videos).
]. There are several reports highlighting the resection of lesions in the upper gastrointestinal tract and colon-rectum by conventional 11/6t OTSC followed by loop resection [
]. The true innovation of the FTRD is that by using a clip-and-cut technique, it is possible to perform the resection soon after the OTSC release in order to avoid abdominal contamination and ensure a safer and faster procedure. The mean time for the procedure in the present study was 50 min, including marking, resection and new inspection. If only the operative phases of clip release and resection are included, then the procedure was completed in less than 8 min. With respect to EMR or ESD, the EFTR provides an objectively higher diagnostic value since it allows to obtain a full-thickness resected sample with a more accurate histopathological evaluation of submucosal, muscular, and serosal layers. EFTR cases of small neuroendocrine tumours of the lower intestine [
]. In these cases, the EFTR clearly represents a minimally invasive alternative to surgery. This technique can also be applied in order to acquire a full-thickness wall tissue sample in patients for whom there is suspicion of impairment of colon motility, such as in Hirschsprung disease [
Up to now, this technique was reported to remove lesions of up to 30 mm. However in two experimental models, maximum sizes for EFTR resection of 40 mm and 54 mm were recently described [
]. In agreement with these findings, a lesion as large as 42 mm was successfully removed by EFTR, suggesting that at least in selected cases the 30 mm cut-off for EFTR in humans can be expanded.
In daily practice, the size of the resection is strictly dependent on the size of the cap as well as the thickness and motility of the colonic wall, which may differ in relation to the localization of the lesion and the presence of fibrosis resulting from previous treatments. In the present study, the size of the resected samples was 26 mm (10–42 mm), in line with data from the literature [
]. The biggest lesion was the scar of incomplete resection (R1 resection) of a mucosectomy, located in the caecum in contiguity to the ileo-caecal valve. The R1 resection scars of the rectum were those that showed a smaller size, which was probably a result of a greater fixation of the rectum walls as caused by fibrosis.
], a full-thickness resection with the FTRD was technically successful and histologically confirmed in all patients. The difference between the 100% success rate of our series with the 94% [
] of the previous ones could be related, at least partially, with different inclusion criteria, such as a greater number of R1 resection scars in our series. Suggestively, based on our data, we may postulate that the EFTR with FTRD could represent the gold standard treatment of R1 resection scars. However, we would also agree that the resection of scars localized in the rectum makes the procedure much more difficult due to the greater resistance of the wall to the traction in the cap. In the present study, which comprised a limited cohort of patients, 10 lesions were not in the rectum. For these lesions, due to the cap size and the high cost of the device, it is advisable to perform a colonoscopy try by using the FTRD prOVE CAP in order to evaluate the progression of the colonoscope from the sigmoid to the caecum, hence accessing the lesion. In addition, a colonoscopy allows the clinician to optimise preparation, which remains an important prerequisite for the resection. In the case of EFTR in the transverse and ascending colon, it is also advisable to fix the sheath of the colonoscope with pieces of tape placed closer to one another, ensuring that they are placed properly on the endoscope in order to avoid the possible friction of the sheath itself.
We observed that the circumferential margins of the lesion, when delineated by the FTRD Marking Probe, are not clearly visible during retraction of the lesion into the cap, leading to the risk of a partial or incomplete EFTR. We prefer to mark the lesion by APC (Erbe APC 300, 25 W) to increase visibility during the traction. It is also necessary to grasp the mid portion of the lesion with the FRTD Grasper to ensure that the entire lesion inside the cap is tractioned. In some cases, it has been useful to add a gentle aspiration to the traction movement of the forceps; however, it is important to underline the potential risks of the EFTR procedure, such as the accidental clipping of extracolonic structures (vessels, small intestine), especially for lesions localized in the transverse or ascending colon.
In case of lesions with marked fibrosis, with poor or absent motility of the wall that would not permit complete inclusion into the cap, it is advisable not to perform the FTRD and instead, to consider a surgical treatment.
The EFTR may offer a simpler and less time-consuming procedure for the treatment of superficial colorectal neoplastic lesions – where standard endoscopic resection is unfeasible – when compared with the alternative treatments, such as surgery or ESD. The major limitations of the system are the maximum size of the lesion to resect and size of cap, which limits endoscopic view and advancement of the scope thorough the sigmoid or colonic flexures.
During the first follow-up colonoscopy (3 months), we were able to observe a spontaneous clip dislocation in 100% of the patients. Endoscopic removal is advisable in cases of persisting OTSC since it may prevent a further treatment in case of incomplete resection [
]; however, there is only minimal data supporting the timing of OTSC removal. Schmidt et al. noted that the clip should not be removed prior to 8 weeks after the EFTR [
The limitations of this study include the limited number of patients, its retrospective design, and the short-term follow up. In particular, further long-term follow up data are necessary to reassure on the radical treatment of superficially invasive cancers. Secondly, we did not assess the overall cost of EFTR procedure. Third, the number of proximal lesions was small, preventing drawing conclusions on the efficacy of EFTR for these lesions. Despite these limitations, we argue that EFTR is a valid alternative to ESD or EMR in the resection of recurrent adenomas with a negative lifting sign, no-lifting lesions and scars of R1 resections. However, further prospective clinical trials are necessary to recommend this as the treatment of choice.
Conflict of interest
None declared.
References
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Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the Australian Colonic EMR (ACE) study.
Colonoscopic full-thickness resection of the colon in a porcine model as a prelude to endoscopic surgery of difficult colon polyps: a novel technique (with videos).
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