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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5528_Библиотеки_им_академика_М_И_Перельмана.pdf
100 S. Sherwani
et al.
Endocytoscopy
EC, which is based on the same principles as light microscopy, can provide magnification of up to 1400-fold, lateral resolution between 1.7 and
4.2 µm, and imaging depth of up to 50 µm.
32–34
EC requires both contact
with the tissue and dye application (crystal violet or toluidine blue for the
cytoplasm and methylene blue for nuclei), produces en face images at fixed
33,34
depths,
ure 17 demonstrates normal colon by EC.
and can assess both structural and cellular changes.33Fig-
35
Although EC systems include
endoscope- and probe-based offerings, they typically have been produced
in limited numbers for specific research applications. Areas of active investigation via EC in the lower GI tract include amoebic colitis, colorectal
cancer detection, and ulcerative colitis scoring.
34
Enteropathy
The body of literature on CLE findings among the various enteropathies
is small with most studies focusing on irritable bowel syndrome (IBS) of
the terminal ileum. The studies are underpowered to determine findings
specific to any one enteropathy (or type of IBS). Nevertheless, they do
seem to share some common findings of barrier disruption, including the
following
36–40
:
1. epithelial breaks leading to intravenous contrast extrusion (Figure 18),
2. cell dropout/epithelial gaps (Figure 19),
3. increased intervillous spaces owing to fluid leak (including contrast),
4. increased intraepithelial lymphocytes.
The above have even been noted in controlled experiments in response
37
to known environmental antigens
36
reproducibility.
They have also been observed in small numbers in
patients with inflammatory bowel disease (IBD).
and demonstrate good interobserver
39
Additional data suggest
that patients with an IBS phenotype can have CLE changes more commonly
associated with IBD.
41
These observations are too preliminary to reclassify
(a)
(b)
Lower Gastrointestinal Tract 101
Figure 17. Colon, (A) EC and (B) Histology.
35
IBS as an inflammatory condition but do lend credence to the idea of an
IBS-IBD disease spectrum. As a reminder, the light microscopic findings
of IBS mirror those of normal histology.
102 S. Sherwani
(a) (b) (c)
et al.
Figure 18. Irritable bowel syndrome, epithelial breaks, CLE. The progression from A to C demonstrates epithelial dysfunction manifesting as contrast leakage.
Figure 19. Irritable bowel syndrome, cell dropout/epithelial gaps, CLE. The image on the left is a
healthy control. The white triangles in the image on the right bracket a gap.
37
40
Inflammation
Infectious, NSAID, and non-specific enteritis
CLE changes of H. pylori, NSAID, and non-specific enteritis share similar
features.
including increased epithelial gaps, lamina propria fluorescein leakage, and
angulated vessels.
cell gaps in comparison with aspirin.
42
In these etiologies, general changes in inflammation are seen
42
It wasnoted that diclofenacis associated with increased
42
Lower Gastrointestinal Tract 103
Changes associated with Whipple’s disease and mycobacterium
avium infections are similar to those described above.
43–45
Additionally, these infectious diseases are associated with the accumulation of
macrophages within the lamina propria. As a result, broadening of the villi
resulting in a pseudo blunted appearance is noted with CLE.
43–45
Also,
the macrophages, appearing as enlarged dark cells, may be seen within the
lamina propria.
43–45
Pouchitis
Assessing the ileal pouch for inflammation after anastomosis is integral in
management of ileal anastomoses.
evaluation of the degree of inflammation within the ileal pouch.
features of inflammationare noted in cases of pouchitis including prominent
bright vessels and dark cells representing inflammatory cells.
important change seen with CLE is villous atrophy and colonic metaplasia.
It is not clear whether true colonic metaplasia occurs within pouchitis, as
it is argued that complete villous atrophy resembles changes in colonic
46
metaplasia.
Regardless, a CLE pattern with daisy-like crypts (similar to
those seen in normal colon) is characteristic of advanced pouchitis.
3
CLE provides a valuable tool for the
3
General
3
Another
3,42, 46
3
Celiac disease
CLE features of celiac disease vary according to the severity of the condition. Changes seen in Marsh 1 patients comprise increased intraepithelial
lymphocytesappearing as dark round structures scatteredwithin the epithe-
47
lium.
Crypt hyperplasiais seen in Marsh 2 patients.
is considered if any crypts are seen on deep imaging.
is seen in Marsh 3 patients; however, the assessment of villous blunting
may be challenging using CLE as it is an en face modality. A confocal
celiac score (CCS) has been proposed to determine the presence of significant villous atrophy.
48
In this scoring system, the percentage of images
demonstrating either villous atrophy or crypt hyperplasia is determined.
A CCS of0.06 (pathological images:normal images/patient) detected celiac
disease with a good sensitivity, however a score of above 0.22 was found
specific.
48
This method required a large number of images to be obtained
48,49
Crypt hyperplasia
48,49
Villous blunting
104 S. Sherwani
Table 1. Celiac disease, Marsh 3, proposed alternative quantitative scoring system.
Feature Score
Shape of villi Normal, long, slender villi
Broad, some distortion
Broad with total loss of villous architecture
Enterocytes Normal, even shape, and distribution
Some distortion of cellular architecture
Gross villous distortion and loss of enterocyte hexagonal arrangement
Goblet cells 0-Normal
1-Decreased
2-Absent
In-folding of villi 0-Absent
2-Present
Inter-villous 0-Absent
bridging 2-Present
Score - 0–10
et al.
Note: Score close to 10 suggestive of disease.
25
and lacked the accuracy needed for diagnosis. An alternative quantitative
scoring system has therefore been proposed for evaluatingMarsh 3 patients
(Table 1).
celiac disease.
25
In this scoring system, a score close to 10 is suggestive of
25
Inflammatory bowel disease, general
Severalstudies examined the in vivomicroscopic differencesbetween ulcerative colitis and Crohn’s disease.
inflammatory infiltrate is possible using IVM techniques and therefore may
aid in characterizing the nature of IBD.
Full thickness inv olvement by inflammation is a characteristic finding associated with Crohn’s disease.
patchy transmural lesions that disrupt the layers of the colon in Crohn’s
disease.
52–55
CLE imaging has been shown to demonstrate slightly different features in Crohn’s and ulcerative colitis. eCLE features more commonly
50,52, 53
52,53
Evaluation of the distribution of
OCT studies have demonstrated
Lower Gastrointestinal Tract 105
Table 2. CLE features for differentiation of Crohn’s disease and ulcerative colitis.
Score
CLE finding Presence Absence
Severe and widespread architectural distortion 3 0
Frankly irregular surface 3 0
Decreased crypt density 3 0
Discontinuous (patchy) crypt architectural abnormality 0 1
Focal cryptitis 0 1
Discontinuous (patchy) inflammation 0 1
Note: Score of 6 or more favors ulcerative colitis.
51
noted in Crohn’s disease include mucosal fissures, focal cryptitis, gran-
50
ulomas, a nd microscopic inflammation involving the terminal ileum.
On
the other hand, ulcerative colitis often demonstrates bifid crypts and continuous inflammation that progresses distally.
50
A recent scoring system was
developed based on CLE features for the differentiation between ulcerative
51
colitis and Crohn’s disease (Table 2)
be 90% sensitive and 97.4% specific for ulcerative colitis.
A score of 6 or more was found to
51
In general, the CLE changes in IBD could be divided into three cate-
gories: 1. normal endoscopic and microendoscopic findings(normal colon),
2. normal endoscopic, abnormal microendoscopic findings (quiescent disease), and 3. abnormal endoscopic and abnormal microendoscopic findings
(active disease).
Crohn’s disease
Like inflammatory processes elsewhere, active Crohn’s disease is often
characterized by vessels with increased permeability and fluorescein leakage in the lamina propria.
the lamina propria and mucosa.
dark patches due to the high nuclear density.
ated with mucosal damage in active disease.
of mucosal and crypt microerosions is seen in active disease.
Microerosions are usually seen as areas of cellular discontinuity and
shedding within the lumen.
56,57
Patchy cellular infiltrate is often noted in
51,56
Cellular infiltrates usually appear as
50,51, 56, 57, 60
58,59
56,57
and are usually associ-
Focal cryptitis in the form
Although an inconsistent fining,
50,51, 56, 57, 60
106 S. Sherwani
et al.
crypt destruction and increased inflammatory infiltrate may manifest as a
decrease in the number of cryptsper field of view.
56,57
This finding contrasts
with theincreased crypts per fieldof view thatare found to be a characteristic
finding seen in quiescent disease.
56
Additional findings described in active
Crohn’s disease includereduction in mucosal goblet cells, mucosal fissures,
and crypt irregularity.
50,51, 56,57
Granulomas are one of the histologic hallmarks of Crohn’s disease, however they are hard to visualize in vivo.CLE
findings suggestive of in vivo visualization of epithelioid granulomas have
been described although descriptiveexamples are yet to be demonstrated.
50
Endoscopically normal microscopically abnormal quiescent Crohn’s
disease is characterized by findings parallel to the architectural changes
of chronic colitis.
56,57,61
Contrary to changes in active disease, quiescent
Crohn’s disease is strongly associated with an increase in goblet cells and
56
crypts per field of view.
Another interesting finding is increased fluorescein leakage within the lumens of the crypts (as opposed to lamina propria
leakage in active colitis).
56
This finding is consistent with the interesting
phenomenon of intestinal epithelial barrier disruption found in inflammatory bowel diseases. Kiesslich et al. first documented increased luminal
fluorescein leakage in the duodenum and ileal eCLE imaging of both ulcer-
62–66
ative colitis and Crohn’s disease patients.
This finding has since been
documented by several studies including the development of a scoring system (Watson score) that grades the degree of intestinal barrier compromise
in Inflammatory bowel disease.
62
The en face architectural distortion associated with chronic Crohn’s disease manifests as an elongated crypt (major
axis:minor axis >1.7:1).
56,61
Additional features of chronicity included
increased microvascular density with tortuous vessels and focal increase in
56
inflammatory infiltrate.
ings in Crohn’s disease.
Figures 20–22 demonstrate common CLE find-
50,67
Ulcerative colitis
Similar to vascular changes seen in active Crohn’s disease, active ulcerative colitis is characterized by increased fluorescein leakage in the
lamina propria.
crypt lumens secondary to epithelial damage associated with ulcerative
50,68–70
Fluorescein may also be seen leaking into the
Lower Gastrointestinal Tract 107
(a)
(b)
Figure 20. Crohn’s, fissure and cryptitis, CLE. eCLE image showing (a) a mucosal fissure (red
arrows) with luminal fluorescein leakage and (b) focal cryptitis (red arrows) seen as dark cellular
infiltrate within crypt lumen associated with mucosal damage.
50
Figure 21. Crohn’s, vascular changes, CLE. eCLE showing vascular changes in mild Crohn’s disease
including hypervascularization with fluorescein leakage and slightly irregular crypts.
50
108 S. Sherwani
et al.
Figure 22. Crohn’s, severe, CLE. eCLE showing changes severe Crohn’s disease including massive
cellular infiltrate, crypt distortion, severe fluorescein leakage, and crypt erosion.
50,68–70
colitis.
Cellular architectural changes are associated with the sever-
67
ity of inflammation. Mild to moderate inflammation is associated with a
decrease in the number of crypts that often appear dilated, tortuous, and
bifid with a reduction in the number of goblet cells.
50,68–70
Severe ulcerative colitis is seen as complete or near complete loss of crypts (ulceration)
and replacement with necrosis.
70
Perhaps more critical is the detection of microscopic changes in
endoscopically normal colon (chronic-inactive/quiescent ulcerative colitis). Architectural changes seen in quiescent ulcerative colitis include
increased crypt diameter (>90µm is considered predictive of relapse),crypt
fusion, and hyperplastic changes, such as star-shaped lumens.
71
The regular honeycomb arrangement of vessels may be preserved, but they appear
brighter.
71–74
However, vascular irregularity and loss of regular honey-
comb arrangement of vessels have also been described in chronic inactive
71–74
colitis.
colitis.
Figure 23 demonstrates common CLE findings in ulcerative
70
Lower Gastrointestinal Tract 109
(a) (b)
(c) (d)
Figure 23. Ulcerative colitis, CLE. Changes of ulcerative colitis ranging from mild to severe. (a)
Microvascular proliferation and mildly irregular crypts. (b) Crypt distortion with interstitial fluorescein
leakage. (c) Bifid crypts, interstitial fluorescein, and luminal fluorescein leakage. (d) Severe UC with
decreased number of crypts. A crypt abscess (triangle) is seen within a crypt.
70
Pseudomembranous colitis
Pseudomembranous colitis may be apparent endoscopically, however,
in vivo CLE features may aid real-time diagnosis and prompt treatment.
In vivo features of pseudomembranous colitis include common features of
inflammation such as cellular and architectural distortion, vascular dilation, and interstitial fluorescein leakage (Figure 24).
75
In addition to fea-
tures of inflammation, visualization of Clostridium difficile bacteria has
75