Introduction
Confocal laser endomicroscopy (CLE) has the potential to allow in vivo endomicroscopy
and, thus, avoid the need to resect nonneoplastic polyps or to resect and discard
small, low grade adenomas when a high-confidence, accurate diagnosis is made. Guidelines
for this strategy have been outlined by the American Society for Gastrointestinal
Endoscopy, among other resources [1]. Because of the extreme (1000-fold) magnification of both endoscopic confocal laser
endomicroscopy (eCLE) and probe-based confocal laser endomicroscopy (pCLE) systems,
maintaining a stable image is challenging.
The incidence of colorectal cancer (CRC) and CRC-related deaths can be reduced by
early detection with methods such as colonoscopy with polypectomy [2]. Currently, more than one-third of resected polyps are nonneoplastic, and greater
than 90 % of neoplastic polyps are low grade tubular adenomas [3]. The cost of histopathologic confirmation of these is substantial, with more than
14 million colonoscopies performed annually in the United States [4]. Screening for CRC with colonoscopy is effective, safe, and widely used in the United
States. Despite these advantages, the reliance on biopsy or polypectomy with ex vivo
histopathologic examination remains a major limitation because of the increased risk
to the patient associated with polypectomy of nonneoplastic lesions, overall cost,
and delay in the final diagnosis.
In this study, we evaluated an image-enhancement technology, CLE, which enables in
vivo histopathologic examination with mucosal analysis at the cellular level. This
is particularly important for evaluating different types of polyps. Real-time assessment
is possible through a high-resolution technique, which provides a 1000-fold magnification
[5] and yields in vivo analysis of cellular components and vascular distribution. Two
different types of CLE systems are currently available. One is integrated to the endoscope
(eCLE) and developed by Pentax (Tokyo, Japan).The other is probe based (pCLE), which
consists of a through-the-scope system from Mauna Kea Technologies (Paris, France)
[6].
The primary aim of this study was to obtain a preliminary assessment of whether the
use of an endoscopic distal attachment cap may enhance probe stabilization in comparison
with free-hand image acquisition, with image quality as the primary outcome measure.
Image quality was assessed by conducting an offline blinded review of images. Our
secondary aims were to explore whether polyp size may be important in the comparison
of image quality and probe stability. We also examined the confidence level and duration
of, as well as compared images obtained with, pCLE, white-light (WL), and narrow-band
(NB) imaging methods. Finally, we measured biopsy time, colonoscope insertion time,
and colonoscope withdrawal time with or without the use of a cap. Comparison of confocal
diagnosis was based on the Miami classification system [7] with regard to the histopathologic findings and distinction of neoplastic polyps
between the 2 study groups.
Patients/Materials and methods
Patients/Materials and methods
The study was approved by the Institutional Review Board of the Mayo Clinic (Jacksonville,
Florida, USA) and was registered at clinicaltrials.gov (NCT01515514; Confocal Endomicroscopy
for GI Neoplasia Study).
A total of 40 outpatients, who underwent planned colonoscopy (January 10 – November
5, 2012) for evaluation of colon polyps, were included in the study. Exclusion criteria
were known polyposis syndromes, inflammatory bowel disease, allergy to fluorescein,
or refusal to provide informed consent.
Just before the procedure was performed, each patient was assigned, through a computerized
randomization system, to 1 of 2 study arms on the basis of whether an endoscopic distal
attachment cap (4 mm, D-201-16403; Olympus America, Center Valley, Pennsylvania, USA)
was used (n = 21, Cap Used) or not used (n = 19, No Cap). Standard colonoscopic imaging
was performed first, followed by injection of 5 mL of 10 % fluorescein (Akorn Pharmaceuticals,
Lake Forest, Illinois, USA). One minute after fluorescein injection, pCLE imaging
commenced and was continued until images of adequate quality, as defined by in-focus,
stable imaging of colonic epithelium, were obtained from representative areas of the
polyps. The probe was maintained 3 to 4 mm distal to the endoscope tip. When a cap
was used, the cap was placed in direct contact with the colon wall and over the polyp
to stabilize the image. Confocal imaging was subsequently performed. To standardize
imaging relative to the fluorescein timing, no more than 3 lesions per patient were
imaged, which was limited to the first 8 minutes after injection. All pCLE images
were captured by the principal investigator of the study (M. B. W.), who has extensive
experience with pCLE (> 500 pCLE cases). The pCLE manipulation, including probe management
and capture of images, was completed by either a research fellow, program coordinator,
or visiting physician, all of whom had prior training. After imaging, each polyp was
removed with snare or biopsy forceps and evaluated by using standard histopathologic
methods.
Because the presence of a cap would not allow blinding during the study, all images
on the Cellvizio system (Mauna Kea Technologies) video were recorded. Each video was
reviewed offline by an expert (M. B. W.), who was blinded to the cap use and image
acquisition method. Technical quality of each video sequence was scored subjectively
by using the results of the histopathologic findings as a reference standard (1 – 5
scale: 1, worst image quality; 3, acceptable image quality; 5, image quality equal
to that of histopathologic findings). Scoring of image stability and motion artifact
was also recorded by using a similar 1 – 5 scale (1, worst image stability; 3, acceptable
image stability; 5, stability equal to that of histopathologic findings).
Statistical considerations
-
The study was designed as a preliminary and pilot study, with the aim of gaining estimates
of accuracy of diagnosis, with the results intended to guide the design of a potentially
larger and powered study. The study was not powered to definitively assess differences
in the techniques. Thus, tests of statistical inference were not performed, because
results can be misleading in small studies.
-
We planned to enroll 40 patients, with the expectation that colonoscopy in these patients
would yield approximately 60 discovered polyps in total, on the basis on many prior
trials involving colon polyps. For the comparison of groups (Cap Used vs No Cap),
we expected around 60 polyps. Because the focus of this study was to gain a preliminary
assessment of the potential utility of the use of a cap to guide future research,
the analysis consisted of descriptive summaries only. Our primary summary measure
was the proportion with a high score for the purpose of imaging quality. A score of
either 4 or 5 was designated as a high score.
Results
Patient characteristics, including age, sex, race, patient history of CRC or adenoma,
family history of CRC, and indication for procedure, were distributed similarly across
the 2 study groups ([Table 1]).
Table 1
Characteristics of 40 patients undergoing colonoscopy (January 10 – November 5, 2012)
with or without an endoscopic distal attachment cap.
|
No Cap
(n = 19)
|
Cap Used
(n = 21)
|
|
Age at procedure, y
|
64 (47, 57, 75, 85)
|
62 (48, 53, 76, 87)
|
|
Sex, male, no. (%)
|
12 (63)
|
11 (52)
|
|
Race, no. (%)
|
|
|
|
White
|
16 (84)
|
18 (86)
|
|
African American
|
2 (11)
|
1 ( 5)
|
|
Hispanic
|
1 ( 5)
|
2 (10)
|
|
Patient history of CRC or adenoma, no. (%)
|
13 (68)
|
14 (70)
|
|
Family history of CRC, no. (%)
|
6 (32)
|
5 (28)
|
|
Indication for procedure, no. (%)
|
|
|
|
Screening
|
1 ( 5)
|
0 ( 0)
|
|
Surveillance average prior polyps
|
1 ( 5)
|
2 (10)
|
|
EMR
|
1 ( 5)
|
3 (14)
|
|
EMR follow-up
|
14 (74)
|
15 (71)
|
|
Other (polypectomy, transanal resection, poor procedure preparation)
|
2 (11)
|
1 ( 5)
|
No Cap, colonoscopy performed without an endoscopic distal attachment cap; Cap Used,
colonoscopy performed with an endoscopic distal attachment cap; CRC, colorectal cancer;
EMR, endoscopic mucosal resection.
The sample median (minimum, 25th percentile; maximum, 75th percentile) is given for continuous variables. Information was unavailable for some
patients regarding patient history of CRC or adenoma (n = 1, Cap Used) and family
history of CRC (n = 3, Cap Used) and, therefore, could not been included in the summaries.
Percentages for race in the Cap Used group sum to 101 % because of rounding.
For all 81 polyps identified, image quality and stability were similar between the
2 study groups. In specific, the proportion of images with a high quality score (4
or 5) was 74 % (28/38) in the Cap Used group versus 79 % (30/38) in the No Cap arm.
We also observed that the use of the cap yielded a slightly lower proportion of images
with high image stability score (45 %; 18/40) in comparison with images collected
without the cap (58 %; 23/40) ([Table 2]). Higher confidence levels were also observed in the Cap Used group, with 84 % (32/38)
versus 68 % (27/40) in the No Cap group ([Table 2]).
Table 2
Offline probe-based confocal laser endomicroscopy (pCLE) image interpretation of 81
polyps resected from 40 patients undergoing colonoscopy (January 10 – November 5,
2012) with or without an endoscopic distal attachment cap.
|
No Cap
(n = 41)
|
Cap Used
(n = 40)
|
|
Image quality, no. (%)
|
|
|
|
1 = worst
|
0 ( 0)
|
0 ( 0)
|
|
2
|
1 ( 3)
|
1 ( 3)
|
|
3 = acceptable
|
7 (18)
|
9 (24)
|
|
4
|
18 (47)
|
17 (45)
|
|
5 = equal to histopathologic findings
|
12 (32)
|
11 (29)
|
|
4 or 5 = high quality
|
30 (79)
|
28 (74)
|
|
Image stability, no. (%)
|
|
|
|
1 = worst
|
2 ( 5)
|
4 (10)
|
|
2
|
8 (20)
|
4 (10)
|
|
3 = acceptable
|
7 (18)
|
14 (35)
|
|
4
|
10 (25)
|
11 (28)
|
|
5 = equal to histopathologic findings
|
13 (33)
|
7 (18)
|
|
4 or 5 = high quality
|
23 (58)
|
18 (45)
|
|
Percent acceptable image
|
70 (10, 43, 90, 95)
|
60 (10, 50, 70, 95)
|
|
Confidence level, no. (%)
|
|
|
|
Low
|
13 (33)
|
6 (16)
|
|
High
|
27 (68)
|
32 (84)
|
|
Diagnosis, no. (%)
|
|
|
|
Hyperplastic/normal tissue
|
26 (63)
|
27 (68)
|
|
Adenoma
|
|
|
|
Low grade
|
11 (27)
|
9 (23)
|
|
High grade
|
1 ( 2)
|
4 (10)
|
|
Traditional serrated
|
3 ( 7)
|
0 ( 0)
|
No Cap, colonoscopy performed without an endoscopic distal attachment cap; Cap Used,
colonoscopy performed with an endoscopic distal attachment cap.
The sample median (minimum, 25th percentile; maximum, 75th percentile) is given for percent acceptable image. Information for some polyps identified
was unavailable regarding image quality (n = 3, No Cap; n = 2, Cap Used), image stability
(n = 1, No Cap), percent acceptable image (n = 1, No Cap), and confidence level (n = 1,
No Cap; n = 2, Cap Used) and, therefore, could not been included in the summaries.
Percentage sums that do not equal 100 % are due to rounding.
Both insertion and withdrawal times were faster with a cap than without a cap (data
not shown). The number of polyps found was similar (n = 40, Cap Used group; n = 41,
No Cap group) ([Table 2] and [Table 3]). Among polyp characteristics, the proportion of lesions that were neoplastic (including
adenoma or traditional serrated adenoma) in the No Cap and Cap Used groups was 46 %
and 40 %, respectively ([Table 2]).
Table 3
Characteristics of 81 polyps resected from 40 patients undergoing colonoscopy (January
10 – November 5, 2012) with or without an endoscopic distal attachment cap.
|
Overall polyps identified
(N = 81)
|
No Cap
(n = 41)
|
Cap Used
(n = 40)
|
|
Polyp size, mm, no. (%)
|
|
|
|
|
1 – 4
|
22 (27)
|
13 (32)
|
9 (23)
|
|
5 – 8
|
16 (20)
|
9 (22)
|
7 (18)
|
|
10
|
14 (17)
|
9 (22)
|
5 (13)
|
|
≥ 15
|
13 (16)
|
3 ( 7)
|
10 (25)
|
|
No size recorded
|
16 (20)
|
7 (17)
|
9 (23)
|
|
|
|
|
|
1 – 9
|
38 (47)
|
22 (54)
|
16 (40)
|
|
≥ 10
|
27 (33)
|
12 (29)
|
15 (38)
|
|
No size recorded
|
16 (20)
|
7 (17)
|
9 (23)
|
|
Prior EMR site, no. (%)
|
24 (30)
|
13 (32)
|
11 (28)
|
|
Site, no. (%)
|
|
|
|
|
Cecum
|
14 (17)
|
8 (20)
|
6 (15)
|
|
Ascending colon
|
20 (25)
|
8 (20)
|
12 (30)
|
|
Hepatic flexure
|
2 ( 2)
|
1 ( 2)
|
1 ( 3)
|
|
Transverse colon
|
11 (14)
|
7 (17)
|
4 (10)
|
|
Splenic flexure
|
1 ( 1)
|
0 ( 0)
|
1 ( 3)
|
|
Descending colon
|
3 ( 4)
|
1 ( 2)
|
2 ( 5)
|
|
Sigmoid colon
|
13 (16)
|
8 (20)
|
5 (13)
|
|
Rectum
|
17 (21)
|
8 (20)
|
9 (23)
|
|
Histopathologic findings, no. (%)
|
|
|
|
|
Hyperplastic tissue
|
17 (22)
|
10 (27)
|
7 (18)
|
|
Other non-neoplasia
|
27 (35)
|
10 (27)
|
17 (43)
|
|
Adenoma
|
27 (35)
|
16 (43)
|
11 (28)
|
|
Traditional serrated adenoma
|
3 ( 4)
|
1 ( 3)
|
2 ( 5)
|
|
Tubulovillous adenoma
|
3 ( 4)
|
0 ( 0)
|
3 ( 8)
|
No Cap, colonoscopy performed without an endoscopic distal attachment cap; Cap Used,
colonoscopy performed with an endoscopic distal attachment cap; EMR, endoscopic mucosal
resection.
Information was unavailable for some polyps identified regarding histopathologic findings
(n = 4, No Cap) and, therefore, could not been included in the summaries. No polyps
were 9 mm. No polyps were in the range of 11 to 14 mm. Percentage sums that do not
equal 100 % are due to rounding.
When comparing diagnostic accuracy (adenoma vs non-adenoma) among different imaging
methods (WL, NB, and pCLE offline and online), we found that the Cap Used group had
slightly higher diagnostic accuracy estimates than were observed for the No Cap group
for all imaging modalities ([Table 4]).
Table 4
Diagnostic accuracy, with the use of white-light (WL), narrow-band (NB), and probe-based
confocal laser endomicroscopy (pCLE) offline and online imaging methods, for 81 (77
evaluable) polyps resected from 40 patients undergoing colonoscopy (January 10 – November
5, 2012) with or without an endoscopic distal attachment cap.
|
Imaging diagnosis
|
No Cap
|
Cap Used
|
|
Normal tissue
(n = 20)
|
Adenoma
(n = 17)
|
Accuracy, no. (%)
(n = 37)
|
Normal tissue
(n = 24)
|
Adenoma
(n = 16)
|
Accuracy, no. (%)
(n = 40)
|
|
WL
|
|
|
26/37 (70)
|
|
|
32/39 (82)
|
|
Hyperplastic/normal tissue
|
14
|
5
|
|
18
|
2
|
|
|
Adenoma
|
|
|
|
|
|
|
|
Low grade
|
5
|
8
|
|
3
|
4
|
|
|
High grade
|
0
|
3
|
|
0
|
7
|
|
|
Traditional serrated
|
1
|
1
|
|
2
|
3
|
|
|
NB
|
|
|
27/36 (75)
|
|
|
33/39 (85)
|
|
Hyperplastic/normal tissue
|
13
|
2
|
|
18
|
1
|
|
|
Adenoma
|
|
|
|
|
|
|
|
Low grade
|
6
|
10
|
|
3
|
5
|
|
|
High grade
|
0
|
4
|
|
0
|
7
|
|
|
Traditional serrated
|
1
|
0
|
|
2
|
3
|
|
|
pCLE offline
|
|
|
26/37 (70)
|
|
|
31/40 (78)
|
|
Hyperplastic/normal tissue
|
16
|
7
|
|
21
|
6
|
|
|
Adenoma
|
|
|
|
|
|
|
|
Low grade
|
2
|
8
|
|
3
|
6
|
|
|
High grade
|
0
|
1
|
|
0
|
4
|
|
|
Traditional serrated
|
2
|
1
|
|
0
|
0
|
|
|
pCLE online
|
|
|
26/37 (70)
|
|
|
32/40 (80)
|
|
Hyperplastic/normal tissue
|
15
|
6
|
|
21
|
5
|
|
|
Adenoma
|
|
|
|
|
|
|
|
Low grade
|
1
|
8
|
|
2
|
4
|
|
|
High grade
|
2
|
2
|
|
0
|
7
|
|
|
Traditional serrated
|
2
|
1
|
|
1
|
0
|
|
No Cap, colonoscopy performed without an endoscopic distal attachment cap; Cap Used,
colonoscopy performed with an endoscopic distal attachment cap.
Some information was unavailable regarding WL imaging diagnosis (n = 1, No Cap; n = 1,
Cap Used) and NB imaging diagnosis (n = 2, No Cap; n = 1, Cap Used) and, therefore,
could not been included in the summaries. Accuracy refers to presumed diagnosis of
adenoma versus hyperplastic/normal tissue.
In both groups, overall image quality was better for lesions measuring 10 mm or greater,
in comparison with lesions measuring between 1 and 9 mm (70 % and 60 % of acceptable
images, respectively). The imaging quality and image stability were similar with and
without a cap ([Table 5] and [Table 6]).
Table 5
Offline probe-based confocal laser endomicroscopy (pCLE) image interpretation of 38
polyps, measuring between 1 and 9 mm, resected from 40 patients undergoing colonoscopy
(January 10 – November 5, 2012) with or without an endoscopic distal attachment cap.
|
Overall polyps identified
(N = 38)
|
No Cap
(n = 22)
|
Cap Used
(n = 16)
|
|
Image quality, no. (%)
|
|
|
|
|
1 = worst
|
0 ( 0)
|
0 ( 0)
|
0 ( 0)
|
|
2
|
1 ( 3)
|
1 ( 5)
|
0 ( 0)
|
|
3 = acceptable
|
8 (23)
|
5 (25)
|
3 (20)
|
|
4
|
19 (54)
|
10 (50)
|
9 (60)
|
|
5 = equal to histopathologic findings
|
7 (20)
|
4 (20)
|
3 (20)
|
|
|
|
|
|
Mean (SD)
|
3.9 (0.7)
|
3.9 (0.8)
|
4.0 (0.7)
|
|
Image stability, no. (%)
|
|
|
|
|
1 = worst
|
3 ( 8)
|
2 ( 9)
|
1 ( 6)
|
|
2
|
7 (18)
|
4 (18)
|
3 (19)
|
|
3 = acceptable
|
11 (29)
|
5 (23)
|
6 (38)
|
|
4
|
10 (26)
|
6 (27)
|
4 (25)
|
|
5 = equal to histopathologic findings
|
7 (18)
|
5 (23)
|
2 (13)
|
|
|
|
|
|
Mean (SD)
|
3.3 (1.2)
|
3.4 (1.3)
|
3.2 (1.1)
|
|
Percent acceptable image
|
60 (10, 40, 70, 95)
|
65 (10, 40, 80, 95)
|
55 (15, 40, 70, 95)
|
|
Confidence level, no. (%)
|
|
|
|
|
Low
|
9 (24)
|
8 (36)
|
1 ( 6)
|
|
High
|
29 (76)
|
14 (64)
|
15 (94)
|
|
Diagnosis, no. (%)
|
|
|
|
|
Hyperplastic/normal tissue
|
29 (76)
|
16 (73)
|
13 (81)
|
|
Adenoma
|
|
|
|
|
Low grade
|
8 (21)
|
5 (23)
|
3 (19)
|
|
High grade
|
1 ( 3)
|
1 ( 5)
|
0 ( 0)
|
|
Traditional serrated
|
0 ( 0)
|
0 ( 0)
|
0 ( 0)
|
SD, standard deviation.
The sample median (minimum, 25th percentile; maximum, 75th percentile) is given for percent acceptable image. Information for some polyps identified
was unavailable regarding image quality (n = 2, No Cap; n = 1, Cap Used). Percentage
sums that do not equal 100 % are due to rounding.
Table 6
Offline probe-based confocal laser endomicroscopy (pCLE) image interpretation of 27
polyps, measuring 10 mm or greater, resected from 40 patients undergoing colonoscopy
(January 10 – November 5, 2012) with or without an endoscopic distal attachment cap.
|
Overall polyps identified
(N = 27)
|
No Cap
(n = 12)
|
Cap Used
(n = 15)
|
|
Image quality, no. (%)
|
|
|
|
|
1 = worst
|
0 ( 0)
|
0 ( 0)
|
0 ( 0)
|
|
2
|
1 ( 4)
|
0 ( 0)
|
1 ( 7)
|
|
3 = acceptable
|
8 (31)
|
2 (17)
|
6 (43)
|
|
4
|
8 (31)
|
4 (33)
|
4 (29)
|
|
5 = equal to histopathologic findings
|
9 (35)
|
6 (50)
|
3 (21)
|
|
|
|
|
|
Mean (SD)
|
4.0 (0.9)
|
4.3 (0.8)
|
3.6 (0.9)
|
|
Image stability, no. (%)
|
|
|
|
|
1 = worst
|
3 (11)
|
0 ( 0)
|
3 (20)
|
|
2
|
4 (15)
|
3 (25)
|
1 ( 7)
|
|
3 = acceptable
|
6 (22)
|
1 ( 8)
|
5 (33)
|
|
4
|
8 (30)
|
3 (25)
|
5 (33)
|
|
5 = equal to histopathologic findings
|
6 (22)
|
5 (42)
|
1 ( 7)
|
|
|
|
|
|
Mean (SD)
|
3.4 (1.3)
|
3.8 (1.3)
|
3.0 (1.3)
|
|
Percent acceptable image
|
70 (10, 40, 80, 95)
|
75 (25, 45, 90, 95)
|
50 (10, 30, 70, 95)
|
|
Confidence level, no. (%)
|
|
|
|
|
Low
|
9 (35)
|
4 (33)
|
5 (36)
|
|
High
|
17 (65)
|
8 (67)
|
9 (64)
|
|
Diagnosis, no. (%)
|
|
|
|
|
Hyperplastic/normal tissue
|
10 (37)
|
4 (33)
|
6 (40)
|
|
Adenoma
|
|
|
|
|
Low grade
|
11 (41)
|
6 (50)
|
5 (33)
|
|
High grade
|
4 (15)
|
0 ( 0)
|
4 (27)
|
|
Traditional serrated
|
2 ( 7)
|
2 (17)
|
0 ( 0)
|
SD, standard deviation.
The sample median (minimum, 25th percentile; maximum, 75th percentile) is given for percent acceptable image. Information for some polyps identified
was unavailable regarding image quality (n = 1, Cap Used) and confidence level (n = 1,
Cap Used). Percentage sums that do not equal 100 % are due to rounding.
When assessing correspondence between the confocal Miami criteria and the histopathologic
diagnosis, we found a stronger association with thickness, darkness, and vessels in
the Cap Used group, but no association with the presence/absence of goblet cells ([Table 7]).
Table 7
Correspondence of Miami classification system[1] with histopathologic findings for 81 (77 evaluable for Miami classification) polyps
resected from 40 patients undergoing colonoscopy (January 10 – November 5, 2012) with
or without an endoscopic distal attachment cap.
|
No Cap
|
Cap Used
|
|
Normal tissue
(n = 20)
|
Adenoma
(n = 17)
|
Correspondence, no. (%)
(n = 37)
|
Normal tissue
(n = 24)
|
Adenoma
(n = 16)
|
Correspondence, no. (%)
(n = 40)
|
|
Crypt class
|
|
|
n/a
|
|
|
n/a
|
|
Round
|
5
|
1
|
|
6
|
0
|
|
|
Stellate
|
11
|
5
|
|
14
|
4
|
|
|
Irregular or villiform
|
2
|
10
|
|
3
|
10
|
|
|
Disorganized
|
1
|
0
|
|
0
|
1
|
|
|
Goblet cells
|
|
|
12/37 (32)
|
|
|
10/40 (25)
|
|
Absent
|
3
|
8
|
|
4
|
10
|
|
|
Present
|
17
|
9
|
|
20
|
6
|
|
|
Epithelial thickness
|
|
|
27/37 (73)
|
|
|
33/40 (83)
|
|
Uniform/thin
|
17
|
7
|
|
22
|
5
|
|
|
Irregular/thick
|
3
|
10
|
|
2
|
11
|
|
|
Epithelial darkness
|
|
|
27/37 (73)
|
|
|
33/40 (83)
|
|
Not dark
|
17
|
7
|
|
22
|
5
|
|
|
Dark
|
3
|
10
|
|
2
|
11
|
|
|
Vessels
|
|
|
26/36 (72)
|
|
|
32/40 (80)
|
|
Thin
|
16
|
7
|
|
22
|
6
|
|
|
Dilated/irregular
|
3
|
10
|
|
2
|
10
|
|
n/a, nonapplicable.
Information for some polyps identified was unavailable regarding crypt class (n = 2,
No Cap; n = 2, Cap Used) and vessels (n = 1, No Cap).
1 Wallace M, Lauwers GY, Chen Y et al. Miami classification for probe-based confocal
laser endomicroscopy. Endoscopy 2011; 43: 882 – 891
Discussion
Overall, this preliminary study did not yield sufficient evidence to support that
the use of a cap improves the quality or stability of pCLE images. This does not mean
that it is not effective, and this trial is still a pilot study that was not powered
to assess for statistical difference. However, a much larger, well-powered study may
identify that image quality is improved with use of a cap.
Although promising, in vivo polyp-discrimination methods have not been widely endorsed.
Methods that require mucosal staining have proved to be cumbersome for screening examinations.
In addition, zoom (magnifying) endoscopes can be fragile and expensive, and regional
differences in magnification offered by available video processors have limited the
reproducibility of NB imaging – discrimination methods outside of Japan and the United
Kingdom [8]. Although results of 1 small western study seem to support that mesh capillary vessel
presence can be accurately assessed without the need for an optical magnification
processor [9], differences in the processors’ diagnostic ability have also been described [10]. Citing the limitations of electronic magnification in visual discrimination, Rex
et al [10] introduced the concept of applying confidence levels to endoscopic prediction in
the hope of improving predictive accuracy. Predictions of polyp histopathologic findings
were made with high confidence 81 % and 92 % of the time for diminutive hyperplastic
and adenomatous polyps, respectively. From this group, high levels of predictive accuracy
were shown for both hyperplastic (95 %) and adenomatous (91 %) lesions [10]. Despite showing that mucosal patterns are highly accurate in predicting neoplasia,
the lower than ideal confidence in predicting hyperplastic lesions (81 %) means that
a large number of lesions would still require polypectomy.
Our group has evaluated advanced endoscopic imaging methods and pCLE for polyp discrimination.
In a large, single-blind trial, pCLE was found to be superior to current state-of-the-art,
NB or Fuji Intelligent Chromo Endoscopy (FICE), imaging. However, in neither method
were critical thresholds needed to avoid the need for histopathologic evaluation reached
[11].Furthermore, pCLE is a cumbersome process that requires exogenous fluorescein dye
and expensive confocal probes.
As with all endoscopic imaging methods, pCLE relies on the ability of the operator
to acquire images of high quality and interpret them with reliability and accuracy
[6]
[11]. Although pCLE offers greater convenience and compatibility with all standard endoscopes,
the free-hand nature of holding the pCLE in contact with tissue presents challenges
to gaining stable, high quality images [12]. Few studies with options to improve image stability have been published to date.
The eCLE systems overcome this by applying suction to the tip of the endoscopes, which
is integrated with the CLE imaging window [13]. A hand-held instrument with the purpose of providing contact force and better confocal
images has been developed that may overcome natural bowel movements and also the subjective
motion from the hand of the operator [14].
Our group previously published a study comparing the accuracy of standard imaging
and pCLE for colorectal polyps. We have generally observed that pCLE has a lower diagnostic
accuracy for imaging small polyps and speculate that this is due to difficulties in
maintaining good probe contact and image stability [15].
A limitation of the current study is that it was performed in a single center that
has substantial experience in pCLE. This experience may reduce the differences between
different techniques (Cap Used vs No Cap) because we have a significant amount of
experience with the free-hand methods. The study was also limited by small sample
size and could only provide preliminary comparisons.
In summary, our study findings do not support that the use of a cap improves image
stability, although it may increase the accuracy of pCLE and other imaging methods
for small polyps. There is still need for larger randomized trials with different
image stabilization techniques or devices when using pCLE technology.
