Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_699_Библиотеки_им_академика_М_И_Перельмана.pdf
88 Pathology of the mesentery
Mesenteric disease manifestation in Crohn’s disease
mucosa and
(b)
Severe
Moderate
Mild
(a)
Regions
of fat
wrapping
Normal
bowel wall
Ulcerated
mucosa
Ulcerated
mucosa
Figure 7.2 (a) Mild, moderate, and severe mesenteric manifestations in Crohn’s disease. (b) With advancing mesenteric
manifestations, the mesentery thickens with the result that the adipovascular pedicles can no longer be distinguished from
adjacent avascular interpedicular areas. With advancing mesenteric manifestations fat wrapping extends over the serosal
surface to involve a greater amount of the circumference.
Fat wrapping and mucosal disease
(b)
Crohn’s disease (primary mesenteropathy) 89
Mesenteric fat wrapping
(a)
Normal mesentery
Normal mucosa
Mesenteric fat wrapping
Abnormal Mesentery
Abnorman mucosa
Figure 7.3 (a) Terminal ileum demonstrating a transition from mild to moderate and then severe fat wrapping inthe termi-
nal ileum. (b) Mucosa corresponding to the regions in (a). Aphthous ulceration is apparent in the region adjacent early fat
wrapping while conuent linear ulceration occurs in the region corresponding to the region of severe fat wrapping. In all
cases, ulceration is conned to the mesenteric pole of the mucosa (i.e., axial polarity).
90 Pathology of the mesentery
be identied radiologically, this involves exposure to radiation [22]. e mesentery cannot presently be examined
endoscopically. Data are emerging indicating that circulating brocytes may have a biomarker potential in this context (Figure7.4)[23].
Circulating brocytes and disease activity in
Crohn’s disease
Fibrocytes can be immunohistochemically identied in
the mesentery of patients with Crohn's disease (Figure7.4)
[8,24,25]. Emerging data indicate they cluster at the
interface between the intestinal serosa and the adjacent
mesentery. From these clusters, they may extend along
connective tissue ramications, into the longitudinal and
circular smooth muscle layers. Circulating brocyte levels
appear to correlate with the CDAI. ey decrease following surgical resection and are signicantly reduced if the
patient undergoes fecal diversion via an ostomy. Although
circulating brocyte levels are increased in appendicitis
and diverticular disease, the increase in Crohn’s disease
appears greater than in either of these inammatory conditions. Circulating brocyte levels appear to be related
to mesenteric disease scores, and thus may provide a
serologic biomarker of mesenteric progression in Crohn’s
disease.
Miscellaneous support for mesenteric
involvement
It is beyond the remit of the current chapter to list all data
supporting a role for the mesentery in Crohn’s disease. Some
additional points should be briey mentioned including
reference to appendicitis, mesenteric substance P, and CRP
production [31–33].
Appendicitis and Crohn’s disease
e incidence of appendicitis increases in Crohn’s disease. Prior appendicectomy is an independent risk factor for surgical recurrence (i.e., severe disease requiring
repeat operations) [8,34–36]. Interestingly, this relationship was hinted at by Crohn etal. [37]. ey presciently
noted that, in cases of appendicitis in patients who developed Crohn’s disease, appendiceal inammation involved
the outer layers of the appendix (i.e., the inner layers were
not involved). is suggests that appendiceal inammation arose due to an exogenous (i.e., mesenteric-based)
rather than an endoluminal trigger (Figure 7.6). e term
“mesoappendicitis” had been coined in reference to this
phenomenon [33,38].
CRP production in Crohn’s disease
Circulating brocyte levels change following
intestinal resection in Crohn’sdisease
As mentioned earlier, circulating brocyte levels decrease
following surgical resection and are signicantly reduced in
patients undergoing fecal diversion via an ostomy (Figure7.4).
Two explanations can account for dierent ndings aer
resection or fecal diversion. e rst is that a key intestinal or
mesenteric cue is removed at the time of excisional surgery,
leading to reduced dierentiation of circulating monocytes
into brocytes. A second explanation is that by performing
a mesenterectomy, the surgeon removes an additional source
of brocytes. Although brocytes are generally described
as derived from circulating monocytes (and hence from
bone marrow), a number of observations support composite
sources in Crohn’s disease. First, brocytes can be identied
in mesenteric mesothelium in Crohn’s disease. Second, culture of mesenteric mesothelium leads to the generation of
mesenteric-derived mesenchymal cells (MMCs). ese comprise of broblasts, activated broblasts, and brocy tes (Figure
7.5). Studies examining the cellular properties of MMCs show
that adhesion, proliferation, and migration correlate with the
CDA I [26–28].
Perhaps more signicantly, these cellular properties
also correlate with circulating brocyte levels [23,29,30].
Collating the earlier ndings, it is possible that mesenteric
mesothelium can transform and may oer an additional
source of mesenchymal cells.
Investigators recently identied a direct linkage between
mesenteric production of CRP and systemic levels in Crohn’s
disease [32]. is was a groundbreaking observation as it
demonstrated how mesenteric events could eect systemic
disease manifestations. Interestingly, similar observations
have been made in several other conditions including metabolic syndrome, atherosclerotic dyslipidemia, and type two
diabetes [39–44]. In each, visceral fat-related derived CRP
is a major determinant of systemic CRP levels.
Mesenteric production of substance P
inCrohn’s disease
e neuropeptide substance P is secreted from mesenteric adipocytes. It stimulates proliferation and reduces
apoptosis in preadipocytes, ndings that may be linked to
fat wrapping [45]. As fat wrapping correlates with transmural inammation, muscular hypertrophy, brosis,
and stricture formation, mesenteric-derived substance
P may play a key signaling role in Crohn’s disease [18].
Mesenteric production of substance P is also linked to
symptoms in irritable bowel disease. It is noteworthy that
the symptoms of both IBS and Crohn’s disease overlap
considerably [46–48].
Summary
In summary, mesenteric disease manifestations closely follow local mucosal and systemic manifestations in Crohn’s
Fibrocytes
(i.e
0.950
circulating monocytes
fibrocyte percentage and CDAI
(c) (d)
+
CD45
and SMA
Fibrocytes clustered
at intestinal surface
., intersection with
mesentery)
Crohn’s disease (primary mesenteropathy) 91
tissue and circulation
Tissue fibrocytes
CD45
+
and SMA
+
near vessels
(a)
+
(b)
8.00
7.00
6.00
5.00
4.00
3.00
Mean (SE) cFC level (%)
2.00
1.00
0.00
*P <0.001*P<0.001
6.46
1.97
Controls Active CD
Study cohort
Fibrocyte percentage in
2.54
Baseline CD
* Independent T test
8
CDAI
6
R=0.92
cfc
4
2
0
y=0.99+0.02*x
100 200
CDAI
Correlation between circulating
300
400
500
2
R
linear=
Figure 7.4 (a) Dual staining of human mesentery in Crohn’s disease with αSMA and CD45. Dual stained cells are
myobrocytes. These are numerous in diseased mesentery in Crohn’s disease. They are mostly observed either within or
nearby a capillary giving the impression that they are recruited to the mesentery. (b) Fibrocytes clustered at the intestinal
surface from which they extended into the outer longitudinal muscle layer along connective tissue septae. (c) Bar chart
depicting circulating brocyte levels in healthy control subjects, in active Crohn’s disease, and in quiescent Crohn’s
disease. (d) Correlation between circulating brocyte levels (y axis) and Crohn’s disease activity index (x axis). A strong
correlation was observed between both parameters.
92 Pathology of the mesentery
Panel showing di˜erent cell types
Cytokeratin CD45+Col l Vimentin+Col l ˜SM A ˜SM A+Cytokeratin
Figure 7.5 Panel demonstrating different mesenchymal cell types that are generated following the exvivo culture of mes-
enteric mesothelium.
disease. ey are hallmarked by pronounced histologic
Anatomy
changes and by a transcriptomic environment that supports brosis, inammation, mesothelial proliferation, and
transformation. e classic model of Crohn’s disease holds
that inammation commences at the mucosa and spreads
outward (becoming transmural) and thereaer aects the
adjacent mesentery. erefore, it is feasible, given the above,
that an alternative model may be involved and that mesenteric events could potentially play an earlier role than previously thought.
Nonrotation and incomplete xation are usually described
as complex areas of pathology. However, they are readily
understood when one considers the intestine and mesentery
are continuous entities in the adult, just as they were in the
embryo. In patients with nonrotation, the typical ndings are
as follows: e second part of the duodenum extends vertically into the right ank rather than crossing the abdominal
aorta. In tandem with the intestine, the mesentery adopts a
similar vertical orientation in the right ank (Figure 7.7a). As
NON- (i.e., MAL) ROTATION
a result, the entire small intestinal gastromesenteric complex
is located in the right ank (Figure 7.7b). In all cases of non-
Non- or malrotation is a primary mesenteropathy.
rotation and nonxation, the le mesocolon, mesosigmoid,
Inflamed adherent
Appendix and mesoappendix in Crohn’s disease
mesoappendix
appendix
Inflammed adherent
Figure 7.6 Appendiceal and mesoappendiceal inammation in Crohn’s disease. Both are secondarily inamed due
to the inammation in the adjacent mesentery.
Volvulus 93
absence of rotation of the mesentery. e condition is the
commonest cause of emergency abdominal presentation in
rst year of life. It may be compatible with life, however, as
many cases are discovered incidentally in adults undergoing radiologic investigation. Fatalities arise when the small
intestinal mesentery t wists (i.e., torsion) around the superior
mesenteric artery root region. It is likely that in those cases
with nonrotation who survive into adulthood, the small
intestinal mesentery has partially attached to the retroperitoneum. is prevents a complete rotation on the superior
mesenteric vascular pedicle. Occasionally in adults, these
adhesions lead to acute or subacute obstruction although
this is rare (Figure 7.7d).
Molecular basis of non (i.e., mal) rotation
In normality, Toldt’s fascia and peritoneal reections normally attach the mesentery to the retroperitoneum [49]. In
nonrotation, fascia and peritoneal reection attach the right
mesocolon to the retroperitoneum, nearer the midline, and
not on the right side of the abdominal cavity. e small bowel
mesentery comes to lie on the right side. Despite this however, it remains continuous with the right mesocolon. us,
the cellular and molecular processes responsible for attachment (i.e., fascia and generation of the peritoneal reection)
remain intact. Given this, it appears that the fundamental
abnormality is lack of rotation (rather than an abnormal or
"mal" rotation). At present, it is not known whether this has
a primarily a mechanical, cellular, or molecular basis.
and mesorectum occur in their usual anatomic positions
(Figure 7.7b). is constant anatomic nding is most likely
related to an anchorage eect exerted by the bony pelvis on
the rectum and mesorectum. As these are secured in place,
the mesosigmoid and le mesocolon are similarly secured.
Given the above, the right colon and mesocolon must
occupy a central position (Figure 7.7b). Although the cecum
is interposed between the small bowel and right colon, variations in the attachment of the ileocecal mesenteric conuence mean that it can be variably positioned (and similarly
so can the appendix) (Figure 7.7c). Occult malrotation is not
infrequently observed in appendicitis, where the appendix
is located in an abnormal location such as the le or right
upper quadrant. e right mesocolon is typically shortened,
and as in normality it is contiguous with the small bowel
mesentery and with the transverse mesocolon.
In summary in nonrotation, the small bowel mesentery,
right, transverse, and le mesentery adopt a concertina-like
conformation from the right to the midline and thereaer
to the le side of the peritoneal cavity (Figure 7.7).
Clinical implications of non (i.e., mal) rotation
e term “malrotation” is really a misnomer and should be
changed to nonrotation, as in most cases, there is a complete
VOLVULUS
Volvulus, like nonrotation, is a primary mesenteropathy.
Volvulus involves twisting of a segment of intestine and
mesentery on its mesenteric attachment.
e general literature abounds in reports of “anomalous”
persistence of the right and le mesocolon, and the manner in which this predisposes to volvulus formation [50–57].
Some descriptions, such as the following, are colorful albeit
incorrect;
… the mesocolon is as anomalous as a cleft
palate.[58]
As we now acknowledge persistence of the mesocolon
intoadulthood, this is no longer regarded as a pathogenic
anoma ly [19,59,60].
True anomalies do arise such as nonrotation (described
earlier). Variations in the degree to which the right mesocolic and mesosigmoidal regions attach to the posterior
abdominal wall are far more frequent. ese are also true
mesenteric anomalies and if sucient, predispose to vol-
vulus formation. In some individuals, there is minimal
attachment of the small intestinal mesentery and right
mesocolon to the retroperitoneum. Minor degrees of
nonattachment or xation are associated with technical
94 Pathology of the mesentery
Malrotation (non-rotation)
(a)
obstruction in mal(non)rotation
in mal(non)rotation(c) (d)
Normal gastromesenteric
confirmation
(b)
Gastromesenteric confirmation
in mal(non)rotation
Appendix
Ladd’s bands
Mesoappendix
Appendix/mesoappendix
Figu re 7.7 2.5D illustrations taken from 3D digital sculpture demonstrating (a) normal small bowel and mesentery and
(b)small bowel and mesentery in non- or malrotation. In the latter, the gastromesenteric complex of the small bowel is
positioned to the right of the midline. (c) Mesoappendix and appendix in mal- (non) rotation. (d) Adhesions observed in
the setting of nonrotation. The adhesions pulled the third part of the duodenum toward the mesentery. The resultant
angulation led to a partial obstruction that required adhesiolysis.
diculty in traversing the colon during colonoscopy and
probably increase the likelihood of loop formation.
Volvulus is frequently observed on the le side when it
involves an elongated sigmoid and mesosigmoid. Volvulus
here is an excellent example of the two factors that are key
in its development. First, most cases of volvulus are associated with an abnormally lengthy sigmoid. If the sigmoid is
lengthy, then the adjacent mesosigmoid will also be lengthy.
Second, the region of the mesosigmoid attached to the retroperitoneum is frequently narrower than one would ordinarily expect. us, the dierential in length between the
attached and the intestinal region of the mesosigmoid contributes to its torsion around the zone of attachment. e
greater the dierential, the greater the risk of torsion.
A similar mechanical phenomenon occurs at the ileocecal region when the terminal ileum and cecum have not
Desmoid tumor 95
attached to the retroperitoneum. In this setting, the apex of
the mesenteric attachment is again narrow and predisposes
to torsion around it. Although the transverse colon and
mesocolon are mobile, volvulus here is much less frequent.
is is due to the attachment of the mesenteric and splenic
components of the exures on either side of the middle colic
adipovascular pedicle.
EPIPLOIC APPENDAGITIS
Appendices epiploicae are variously sized and shaped adipose collections attached to the colon. Although some suggest they derive from tenia coli on the antimesenteric side
of the colon, their distribution would not appear to support this [61]. In thin individuals, they are minimal, while
in adipose patients they are widespread and may carpet
the colonic surface. In these circumstances, they appear to
coalesce with the mesentery and can be dicult to dierentiate from the latter. Given these similarities, it is suggested
they may represent an ectopic form of mesentery. at
being so, then their inammation or infarction is a primary
mesenteropathy.
ey have paired arteries and one draining vein [62].
Anatomically, they are greatest number in the cecum and
sigmoid colon [63]. Torsion of their base or thrombosis
of a draining vein can lead to vascular compromise, ischemia, infarction, and inammation. e pain experienced
by the patient is somatic in nature and, not surprisingly,
can be mistaken for intestinal inammation in that region.
Cecal epiploic appendagitis may mimic appendicitis, while
sigmoid epiploic appendagitis may mimic diverticulitis
[64,65]. Epiploic appendagitis or infarction is thus a challenging diagnosis with a broad dierential.
While their function is unknown, there are several
hypotheses. ese include bacterial sampling, facilitation
of colonic absorption, and protection of colonic blood supply (i.e., when the main vasculature has collapsed [66]).
Although evidence to support these roles is limited, identication of lymph nodes within epiploicae may be considered
supportive.
Epiploicae can exert an important barrier or buer
eect, restricting colonic perforation and inammation to
the zone immediately surrounding the colon. A number of
cases have been reported where an intestinal perforation
was contained by the fat of overlying appendices epiploicae.
Figure 7.8a and b illustrate perisigmoidal appendices epi-
ploicae that limited intraperitoneal contamination following an underlying diverticular perforation.
MESENTERIC ISCHEMIA
and thrombus, mesenteric venous thrombus, and nonocclusive mesenteric ischemia [67]. is surgical emergency
requires prompt diagnosis and treatment. Development of
symptoms can be acute or chronic. Acutely, patients classically present with abdominal pain out of proportion with
clinical ndings. As the acute ischemic event progresses,
metabolic abnormalities occur that can progress to multiple organ dysfunction [68]. e nonspecic nature of
the acute presenting complaint, along with rapid progression of ischemia, contributes to a perioperative mortality
of 44%–90% [69]. When surgical intervention is initiated
within 12 hours of onset of symptoms, survival rates can
reach 72.3% [70]. e same study found that only 20% of
patients survived when surgery was delayed to between
24and 48 hours. In chronic mesenteric ischemia, the clinical pattern oen resembles that of angina pectoris or claudication. Following a meal, increased splanchnic blood
ow is insucient to meet the metabolic requirements of
the bowel producing mesenteric angina [71]. Sitophobia,
weight loss, and nausea and vomiting commonly occur [72].
Intervention generally requires bypass of a narrowed segment. Conservative management is described involving
anticoagulation with close monitoring. Resolution in these
contexts is likely due to the development of collateral vasculature. Endovascular repair (angioplasty and stenting)
are emerging treatment modalities [73].
INTERNAL HERNIATION
If this arises due to a defect in the mesentery then it falls
into the category of primary mesenteropathy. Any defect in
the continuity of the mesentery may lead to internal herniation of abdominal viscera. Internal hernias are a rare cause
of small bowel obstruction. Reported incidences vary from
0.5% to 5.8% [74]. Transmesenteric hernias account for 8%
of all internal hernias [75]. Defects in the mesentery can be
congenital or due to surgery, trauma, inammation, or circulatory pathology [76]. irty-ve percent of transmesenteric hernias occur in pediatric populations aged between
3 and 10years [75]. e increased frequency of congenital
defects in attenuated or avascular regions of mesentery,
combined with their high prevalence in infants with atretic
bowel segments, points to an association with prenatal
intestinal ischemic events [75]. Mesenteric defects in adults
are more likely due to previous intra-abdominal surgery,
abdominal trauma, or intraperitoneal inammation [75].
Mortality rates are high at 50% [74]. e lack of a hernial
sac allows large amounts of bowel to herniate [75]. e size
of the defective aperture dictates the risk of strangulation,
ischemia, and necrosis [75].
As mesenteric ischemia is a vascular disorder of the mesentery, it falls into the category of primary mesenteropathy.
Occlusion of the vascular supply of the mesocolon results
in ischemia and necrosis of the bowel. ere are three
principal pathological causes: mesenteric arterial embolus
DESMOID TUMOR
Desmoid tumors frequently develop in the mesentery and
should be considered as a primary mesenteropathy [77].
ese are benign, broblastic proliferations that invade
96 Pathology of the mesentery
Contained sigmoid perforation
Epiploicae
(a)
(c)
Epiploical fat
limiting
perforation
(b)
Forceps in
perforated
diverticulum
Mesosigmoid
Sigmoid mucosa
Figure 7.8 (a) Postoperative image of a colonic perforation contained within the appendices epiploicae of the
colon. (b) Postoperative image of the mesosigmoid demonstrating clear thickening and edema of the mesosigmoid.
(c)Postoperative image of mucosa in specimen from A and B, pointing to the perforation.
locally, have high rates of recurrence, but do not metastasize [78]. Genetic, endocrine, and trauma-related factors
are linked to their etiology. Desmoid tumors are associated with familial adenomatous polyposis, multiparity,
and postsurgical scars [79]. Mutations within genes coding for adenomatous polyposis coli and beta-catenin are
implicated [80]. Although they lack metastatic potential,
they progress locally and can ultimately compromise mesenteric vasculature or cause obstruction. ere are several
treatment modalities, but surgical excision remains the
mainstay [78]. Postoperative radiotherapy reduces the rate
of local recurrence [78].
Mesentery
Mesenteric cyst
Secondary mesenteropathies 97
IgG4-RELATED SCLEROSING
MESENTERITIS
IgG4-related sclerosing mesenteritis is an intra-abdominal
manifestation of IgG4-related disease. IgG4-related disease can aect virtually any organ and mesenteric lesions
are characterized by lymphoplasmacytic inltrate and
storiform brosis [88]. Obliterative phlebitis accompanies
plasma cell inltrations. Patients present with nonspecic
symptoms such as abdominal pain, and imaging reveals a
mesenteric mass [89]. Immunosuppression is the mainstay
of treatment. Glucocorticoids are the rst line of therapy
while refractory cases are treated with disease-modifying
antirheumatic drugs or rituximab [89].
MESENTERIC NEUROLOGIC PATHOLOGY
Mesenteric
cyst
Figure 7.9 Intraoperative image of a mesenteric cyst on
the medial aspect of the mesosigmoid. The cyst contained clear uid and had a smooth inner surface. It was
an incidental nding at surgery.
MESENTERIC CYSTS
A rare form of primary mesenteropathy, mesenteric cysts are
more likely to develop on the mesentery of the small bowel or
right colon [81] (Figure 7.9). While the etiology is unknown,
developmental abnormalities of mesenteric lymphatics may
play a role [82]. ey can present clinically in a broad range
of manners, including asymptomatic abdominal swelling,
chronic abdominal pain or as an acute abdomen secondary
to torsion, infection, or hemorrhage into the cyst itself [83].
SCLEROSING MESENTERITIS
Sclerosing mesenteritis includes a range of conditions
characterized by chronic inammation, brosis, and
(sometimes) necrosis of the mesenteric organ. Mesenteric
lipodystrophy, mesenteric panniculitis, and IgG4-related
sclerosing mesenteritis are included in this class of primary
mesenteric abnormality. Although its etiology remains
unknown, reports suggest links with aberrant autoimmunity or previous abdominal surgery [84].
a paraneoplastic phenomenon although it has been
observed in the absence of a background malignancy
[85,86]. Patients with MP may present with an abdominal mass, pain, nausea, vomiting, or altered bowel habit
[84]. Systemic manifestations including anorexia, weight
loss, or fever can be prominent [84]. Treatment is usually
based on immunosuppression with corticosteroids and
azathioprine, perhaps reecting a primary immunologic
or inammatory basis [87].
Mesenteric panniculitis is classically described as
e intestine receives postganglionic sympathetic and
parasympathetic nerves that regulate myriad functions.
ese nerves are derived from three main ganglia at
the origins of the celiac trunk, the superior and inferior
mesenteric arteries. Apart from these assertions, there
is a dearth of information describing the relationship of
postganglionic nerves to the mesentery. Recent clarication of mesenteric structure indicates that postganglionic
nerves must enter and traverse the mesentery along with
major vessels. At the intersection between mesentery and
adjacent gastrointestinal tract, they penetrate the outer
layers of the latter and ultimately reach Meissner’s and
Auerbach’s plexus.
e enteric nervous system (ENS) regulates peristalsis,
secretion, absorption, local inammation, and immune
responses [90]. During embryogenesis of the ENS, the
mesentery acts as a conduit for enteric neural crest cells
migrating from midgut to hindgut regions. As a result, the
development of a mesentery in the rst instance is essential
for eective innervation of the hindgut [91]. It has been suggested that Hirschsprung’s disease arises from a failure of
transmesenteric migration of enteric neural crest cells [90].
Incomplete mesenteric migration of neural crest cells is linked
to multiple endocrine neoplasia, neuroblastoma, conotruncal heart defects, and Waardenburg syndrome [92]. A delay
in ENS maturation may be responsible for the deranged
motility seen following surgical correction of gastroschisis
[93]. e later is associated failure of development of the
interstitial cells of Cajal, cells analogous to cardiac pacemaker cells.
Although rare, terminal ileal mesenteric schwannomas
have been reported, pointing to a distribution of neural tissue within the mesentery [94].
SECONDARY MESENTEROPATHIES
ese are abnormalities that arise outside the mesentery but
which can progress to involve the mesentery through either
direct or systemic spread.