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68 Toldt’s fascia
24. Culligan, K. etal., A detailed appraisal of mesocolic
lymphangiology—An immunohistochemical and stereological analysis. J Anat, 2014. 225(4): 463–472.
25. Adams, S.D. and M.P. Stanton, Malrotation and intestinal atresias. Early Hum Dev, 2014. 90(12): 921–925.
26. Marine, M.B. and B. Karmazyn, Imaging of
malrotation in the neonate. Semin Ultrasound
CTMR, 2014. 35(6): 555–570.
27. Tackett, J.J., E.D. Muise, and R.A. Cowles,
Malrotation: Current strategies navigating the
radiologic diagnosis of a surgical emergency. World
J Radiol, 2014. 6(9): 730–736.
28. Ballesteros Gomiz, E. etal., Intestinal malrotation—
Volvulus: Imaging ndings. Radiologia, 2015. 57(1):
9–21.
29. diZerega, G., Peritoneal Surgery. Springer, New York,
1999, pp. 39–51.
30. Li, L.J. etal., Progress in laparoscopic anatomy
research: A review of the Chinese literature.
WorldJGastroenterol, 2010. 16(19): 2341–2347.
31. Okazaki, T. etal., Toldt’s fascia ap: A new technique
for repairing large diaphragmatic hernias. Pediatr
Surg Int, 2005. 21(1): 64 –67.
32. Sehgal, R. and J.C. Coffey, The development of
consensus for complete mesocolic excision (CME)
should commence with standardisation of anatomy and
related terminology. Int J Colorectal Dis, 2014. 29(6):
763–764.
33. Coffey, J.C. and P. Dockery, Colorectal cancer:
Surgery for colorectal cancer—Standardization
required. Nat Rev Gastroenterol Hepatol, 2016.
13(5): 256–257.
34. Zhang, C. etal., Perirectal fascia and
spaces:Annulardistribution pattern around the
mesorectum.DisColon Rectum, 2010. 53(9):
1315–1322.
35. Coffey, J.C. etal., An appraisal of the computed
axial tomographic appearance of the human
mesentery based on mesenteric contiguity from
the duodenojejunal exure to the mesorectal
level.EurRadiol, 2016. 26(3): 714–721.
36. Juanes, J.A. et al., Application of the “Visible Human
Project” in the eld of anatomy: A review. Eur J
Anat, 2003. 7: 147–159.
Mesenteric physiology
J. CALVIN COFFEY, RISHABH SEHGAL, AWAD M. JARRAR, AND MATTIAS SOOP
6
Aim 69
Introduction 69
Visceral adiposity 69
Mesenteric cytokine production 70
Mesenteric production ofC-reactive protein 70
Migration during embryologic development 70
Mesentery as a regulatory hub 71
Mesenteric mesothelial plasticity 74
Form follows function.
Louis Sullivan
AIM
is chapter will discuss evidence supporting the suggestion that the mesentery is ideally positioned to sample signals and regulate systemic and local activities in response
to these.
INTRODUCTION
In the past, it was thought the sole function of the mesentery
was to provide a scaold within which blood vessels could
pass to and from the gastrointestinal tract [1–7]. While
this is partially correct, additional functions have become
apparent and led to an increase in research in mesenteric
physiology. e data from which to draw on for this subject are considerable and beyond the scope of a summative
review such as this. However, the key points and supportive
information can be emphasized. Perhaps most importantly,
the histologic contiguity that exists between the intestine,
mesentery, and body proper means that the mesentery
occupies a unique anatomic position (Figure 6.1) [6–10]. It
is interposed between the intestine and body proper and
thus optimally positioned to orchestrate systemic responses
to environmental cues (and vice versa) (Figure 6.1) [3,9,10].
is chapter will demonstrate that the mesentery is not
Mesenteric mesothelial plasticity and intra-abdominal
pathology 74
Mesothelial secretion and absorption of peritoneal uid 75
Mesothelial lymphatics 76
Greater omentum 76
Future studies 79
Summary 79
References 79
merely a bystander in homeostasis but that it plays a central
role across a range of processes.
VISCERAL ADIPOSITY
e past two decades have seen increasing recognition of
the importance of visceral adiposity in regulating a range
of homeostatic processes within the body [11–21]. Visceral
adiposity is a collective term for adipose tissue whose venous
return is through the portal and not the systemic circulation (i.e., greater omentum, small bowel mesentery, and
retroperitoneum) (Table 6.1) [22–36]. Many argue that fat
in and surrounding abdominal viscera should be included
in the term. Even to the present, however, it is rare for the
mesocolon to be included in appraisals of visceral adiposity.
As we now acknowledge that the mesocolon is a substantive entity, spanning the small and large bowel, it follows it
should also be included in the term (Figure 6.2) [37]. When
visceral adiposity is considered in this manner, it is readily
apparent that the mesenteric component is the largest.
Table 6.1 summarizes the activities associated with dif-
ferent fat depots including those contributing to visceral
adiposity. In keeping with trends to date, the mesocolon
is not included. It is imperative that the adipose activities
listed should be characterized within the mesocolon. is
represents an avenue for future research.
In an intriguing article entitled “Is visceral adiposity
the enemy within,” Tracy etal. argued in support of links
69
70 Mesenteric physiology
Mesenteric and intestinal continuity
Mesenteric
connective
tissue
Intestinal
connective
tissue
Figure 6.1 2.5D snapshot of a 3D digital model demonstrating the mesentery and adjacent intestine. The layers
of the intestine are demonstrated. Contiguity occurs in
the connective tissue between the mesentery and adjacent intestine.
between visceral adiposity and homeostatic processes
suchinammation, brinolysis, and coagulation [38]. ey
demonstrated how numerous diseases result from derangements in these and other activities. e association between
visceral adiposity and homoeostasis then led to the suggestion that variations in visceral adiposity themselves
contribute to disease development. Indeed, populationbased studies examining the correlation between visceral
adiposity and the development of atherosclerosis support
this argument [38–44]. Increases in visceral adiposity have
recently been associated with atherogenic dyslipidemia,
metabolic syndrome, and diabetes [45–51]. Future studies
should examine if mesenteric and mesocolic components
of visceral adiposity contribute in a dierential manner to
disease development.
produce cytokines. It is important to investigate this suggestion at all mesocolic levels.
Data suggest that in Crohn’s disease, mesenteric cytokine production diers between inamed and noninamed
mesentery. In Crohn’s disease, mesenteric abnormalities
appear to precede and drive mucosal and gastrointestinal
abnormalities [58–73]. As Crohn’s is thought to involve
environmental factors (i.e., bacteria) within the gutlumen,
these observations indicate that mesenteric cytokine production is inuenced by gastrointestinal bacteria. Moreover, it suggests that mesenteric cytokine production plays
a role in intestinal inammation and derangements thereof
[59,61,74–80].
MESENTERIC PRODUCTION
OFC-REACTIVE PROTEIN
C-reactive protein (CRP) is an acute phase protein that
will be considered separately given recent ndings [81]. In
the past, the liver was regarded as the main source of CRP.
e mesentery has recently emerged as a further, though
somewhat unexpected, source. In a landmark study,
Peyrin-Biroulet showed that mesenteric (and not hepatic)
production of CRP is a major determinant of systemic
CRP in patients with Crohn’s disease [69].
Amato et al. noted a correlation between visceral
adiposity, increased systematic CRP, and the development
of diabetes [20,45,82]. In the non-overweight obese, visceral
fat is signicantly increased compared with subcutaneous
fat [83–85]. is imbalance is linked with alterations in
CRP that correlate with abnormalities in insulin resistance
[85–90]. us, it would appear that ratios between dierent fat depots inuence systemic CRP and glycemic control. is observation, if it holds, could have far-reaching
implications.
MIGRATION DURING EMBRYOLOGIC
DEVELOPMENT
MESENTERIC CYTOKINE PRODUCTION
e mesentery is a major source of cytokine production.
e list of mesenteric cytokines is increasing and pres-
ently includes adipophilin, perilipin, resistin, and leptin
(Table 6.2) [16,52–54]. Alterations in the production of
these have also been linked to metabolic syndrome, atherosclerosis, and diabetes. ese associations point to roles
for mesenteric cytokines in glycemic and lipid regulation in
general. Most studies examining visceral adiposity-associated cytokine production focus on outputs from the greater
omentum and small intestine [29,55–57]. e mesocolon
has been largely excluded from these evaluations. Given
similarities in embryologic origin, adipose composition
and venous return (i.e., through the portal system), it is
reasonable to suggest that separate mesocolic regions also
Increasing data suggest that the mesentery provides a
platform along which several cell types migrate during
embryogenesis, to reach the intestine. Support for this
comes from observations of connective tissue and vascular continuity between the intestine and the mesentery.
Nishiyama et al., in Nature Neuroscience 2012, demonstrated a remarkable cellular journey made by neural crest
cells as these migrate through the dorsal mesentery to reach
the intestine. Once they reach the intestine, they migrate
along its longitudinal axis to populate the entire enteric
nervous system (Figure 6.3) [91]. While Nishiyama’s paper
demonstrated the importance of the mesenteric scaold
for cellular migration, it could also explain the development of gastromesenteric neuroendocrine abnormalities.
Neuroendocrine tumors are thought to arise from neural
crest cells [92]. Itisfeasible thataltered migration of neural
Mesentery as a regulatory hub 71
Table 6.1 Properties of various white adipose tissue depots in nonobese and obese humans
Study Year Journal Variable Nonobese Obese Reference
Fried
etal.
Kraunsøe
etal.
Hoffstedt
etal.
Ray etal. 2009 Lipids Health
Ray etal. 2010 Lipids Health
Ray etal. 2011 Lipids Health
Bonen
etal.
Hou etal. 2009 Obesity Lipogenesis: DGAT
Virtanen
etal.
Drolet
etal.
Ortega
etal.
Erman
etal.
Abbreviations: DGAT, diacylglycerol acyltransferase; FAT/CD36, fatty acid transporter/cluster of differentiation 36; GHR, growth hormone
1993 J Clin Invest Adipocyte size Not determined Smaller in OM fat than
SAT in women
2010 J Physiol Mitochondrial
number and
respiration rate
1997 J Lipid Res Lipolysis rate No differences
Basal and
Dis
Dis
Dis
2006 Int J Obes Fatty acid
2002 J Clin
Endocrinol
Metab
2009 Obesity Adiponectin release
2009 Obesity Expression of
2011 Int J Obes Expression of
receptor; HSL, hormone-sensitive lipase; NA, noradrenaline; OM, omental; SAT, subcutaneous adipose tissue; TRα, thyroid receptor α;
VS, visceral.
NA-induced
lipolysis in
adipocytes
HSL mRNA and
protein levels
Perilipin mRNA and
protein levels
transporter
FAT/CD36 protein
expression
activity
Insulin-stimulated
glucose uptake
by isolated
adipocytes
thyroid hormone
receptors
growth hormone
receptor
Not determined Greater mitochondria
+ higher respiration
rates in OM vs. SAT
Higher in OM vs. SAT [31]
between OM and
SAT adipocytes
Not determined Lower in OM [35]
mRNA expression
lower in OM fat vs.
SAT
mRNA expression
similar in OM fat vs.
SAT; 2× higher
protein level in OM
fat vs. SAT
Higher by 50% in VS
vs. SAT
2× higher in OM fat
vs. SAT
Higher in VS vs. SAT Similar as in nonobese
Similar in OM and SAT Reduced in OM and
Similar in OM and SAT TRα and TRα1 mRNA
Higher GHR mRNA
levels in OM fat than
in SAT
Similar as in lean
subjects; in both
depots mRNA 3×
higher than in lean
women
2× lower mRNA level
in OM fat vs. SAT;
similar protein level
in both fat locations
Similar in VS and SAT
depots
Similar in OM fat and
SAT
men
unchanged in SAT
fat
increased in SAT vs.
OM fat
Lower GHR mRNA in
OM fat and SAT
than in lean subjects
[27]
[33]
[35]
[35]
[28]
[32]
[36]
[29]
[34]
[30]
crest cells through the mesentery and intestine predisposes
to mesenteric neuroendocrine tumors later in adult life.
MESENTERY AS A REGULATORY HUB
Emerging evidence suggests that intestinal bacteria regulate
mesenteric events and that these in turn control immunologic responses within adjacent intestine. Derangements
along this immunologic axis are increasingly thought to
occur in inammatory bowel disease and could also play a
greater role in several forms of gastrointestinal inammation [93–97]. Increasingly, the mesentery is being viewed
as a regulatory hub, or signal box, and that this function is
played out on a connective tissue platform, into which adipocyte, mesenchymal, and immunologic cells feed molecular contributions.
72 Mesenteric physiology
Visceral adiposity
Ascendin
mesentery
g
colon
Right
mesocolon
Small intestinal
Ileum
Figure 6.2 Intraoperative image demonstrating the scale of the contribution made by the small intestine and right
mesocolon to visceral adiposity. The small intestinal mesentery and right mesocolon are continuous, thus supporting the
inclusion of the mesocolon in the umbrella term of “visceral adiposity.” There is a substantial mesenteric tissue mass at the
ileocecal junction. Lymph nodes are apparent throughout.
Table 6.2 Mesenteric cytokine production in Crohn’s disease
Study Year Journal Cytokine Expression Reference
Sideri etal. 2015 Cell Mol Gastroenterol
Tacr-1/-2, IL-17A Increased [107]
Hepatol
Leal etal. 2013 Int J Clin Exp Med LC3-II Reduced [108]
TLR-4 No difference
F4/80 No difference
IL-1β No difference
IL-6 No difference
Kredel etal. 2013 Gut IL-10, IL-6, TNF-alpha Increased [66]
Jung etal. 2013 Cytokine IL-6, IL-4, IL-13 Increased [109]
Peyrin-Biroulet etal. 2012 Gut CRP Increased [69]
Rodrigues etal. 2012 Clin Exp Immunol CRP Increased [80]
adiponectin Decreased
Leptin No difference
Sibartie etal. 2010 Inamm Bowel Dis TNF-alpha Increased [110]
IL-8 Increased
Karagiannides etal. 2006 Proc Natl Acad Sci USA NK-1R, IL-8 Increased [111]
Schäfer etal. 2006 J Gastroenterol Hepatol RANTES Increased [71]
Paul etal. 2006 Inamm Bowel Dis Adiponectin Increased [112]
IL-10 Increased
Macrophage colony-stimulating factor Increased
Leptin Increased
migration inhibitory factor Increased
Resistin No difference
Interleukin-6 No difference
Monocyte chemotactic protein-1 No difference
Schäfer etal. 2006 J Gastroenterol Hepatol VEGF No difference [113]
Yamamoto etal. 2005 Gut Adiponectin Increased [73]
IL-6 No difference
Barbier etal. 2003 Gut Leptin Increased [58]
Desreumaux etal. 1999 Gastroenterology TNF-alpha Increased [60]
Intestinal
Migration of neural crest cells
Dorsal mesentery
neural crest
Migration
Migration
Neuroendocrine
cell
Developing
central nervous
system
Figure 6.3 Schematic illustration of migration of neural
crest cells across the mesentery to reach the proximal
intestine. From there, they then migrate distally to populate the entire intestine.
Over the past decade, increasing data have accumulated
demonstrating a key role for mesenteric-based immune
cell types. Wei etal. [98] showed that mesenteric B cells
inhibit the development of CD4+ T cell–induced colitis.
ey achieve this by rst homing to mesenteric nodes
and then altering recruitment of CD4+, CD8α+ T cells to
adjacent intestinal mucosa [98] (Figure 6.4). Wei et al.
Mesentery as a regulatory hub 73
suggested that mesenteric lymph node–based B cells are
protective and indeed essential in regulating homeostasis in adjacent intestinal mucosa. eir ndings indicate
that mucosal events are directed from mesenteric lymph
node–derived immunologic and cellular activities and
involve coordinated interactions between B cells, T cells,
and NKcells [98].
Hammerschmidt et al. further explored this phenom-
enon [99]. ey demonstrated that stromal cells in mesenteric lymph nodes were crucial for imprinting surface
α4β7-integrin and CCR9 on T cells. Following imprintation, T cells then homed to adjacent intestine, a phenomenon referred to as “gut tropism.” Hammerschmidt etal.
suggest that gut homing T cells can only be generated in a
permissive lymph node environment [99].
In a landmark study, Diehl et al. demonstrated that
luminal microbiota can regulate the tracking of commensal organisms to mesenteric lymph nodes [100]. Under
certain conditions (including antibiotic-induced dysbiosis
and Myd88 deciency) commensal tracking is altered.
eirndings point to an important role for the microbial
ecology in regulating the delivery of enteric antigens to
mesenteric lymph nodes [100].
Using an adoptive model of murine inammatory
bowel disease, Karlis et al. identied adoptively transferred dendritic cells in mesenteric lymph nodes [101].
eir homing to mesenteric nodes preceded the development of mucosal abnormalities. Others have shown
that radiologic signs of visceral adiposity occur in early
Bacteria
Colitis
˜4°7
Bacterium
–
T
cell
CCR9
submucosa/mucosa
Translocation
–
+
CD4
T cell
Homing
–
Inhibit
CD4
Mesenteric
lymph node
+
, CD8
T cell
+
Recruited
B
cell
Stromal
cell
CCR9 expression
+
T
cell
+
˜4°7 expression
Body
B cell
Figure 6.4 Schematic illustration of the cellular and molecular interactions that occur in mesenteric lymph nodes and
effects on adjacent mucosal inammation and immunity.
74 Mesenteric physiology
Crohn’s disease, prior to the development of mucosal disease [22,101–106].
When collated, these ndings demonstrate (Table 6.2) a
key role for mesenteric lymph nodes in coordinating mucosal inammatory and immunologic events in a manner
regulated by local microbial ecology. As many of these studies have been conducted in murine models, similar studies
should be undertaken in the human context.
MESENTERIC MESOTHELIAL PLASTICITY
Increasing evidence points to plasticity in mesenteric mesothelium, which has been partially dealt with in Chapter 4
(Table 6.3) [114–119]. Balogh etal. demonstrated that under
inammatory conditions, mesothelial cells separate from
the underlying basal lamina and transform to spindleshaped cells with increased release of pro- inammatory
cytokines including TGF-β [120]. Several studies examining submesothelial connective tissue, identied cells with
immunohistochemical features overlapping mesothelial
and mesenchymal cell types. Others suggest that mesenteric
mesothelium contains a subpopulation of cells with pluripotential properties [121,122].
We recently noted that when mesenteric mesothelia
are expanded exvivo, they transform into spindle-shaped
cells in a TGF-β-dependent manner. ese are mesothelium-derived mesenchymal cells and include a mixture of
activated broblasts, brocytes, and myobroblasts. We
examined their properties in Crohn’s disease and found
these correlated with disease activity, as well as circulating
brocyte levels (Figure 6.5) [37,123–126].
Taken together, these ndings indicate that mesenteric
mesothelium is not inert and does not simply function as
a barrier across which peritoneal dialysate is absorbed or
created [127]. Instead, it has a regenerative capacity that,
when one considers the mesentery is one of the largest
organs in the body, could be substantial (Figure 6.6) [37].
MESENTERIC MESOTHELIAL PLASTICITY
AND INTRA-ABDOMINAL PATHOLOGY
Although this topic will be expanded on in detail in the
following chapter, it merits reference in this chapter.
e concept that mesenteric mesothelium can transform
into mesenchyme could have major implications in several
pathologic contexts. In abdominal wall hernia, a mesothelial
sac develops that can reach sizeable proportions depending
on the size of the hernia. In inguinal herniae, a mesothelial
extension (the processus vaginalis) extends into the inguinal canal and permits extrusion of abdominal contents into
the canal [128].
Postoperatively, peritoneal mesothelium regenerates
and lls in mesothelial defects within 48–72 hours
[129–133]. Neo-mesothelialization is also associated with
development of mesenchyme and a combination of both
occurs in adhesions. Adhesions dier considerably in morphology and cellular composition but invariably involve
a combination of mesothelial and mesenchymal events in
varying proportions. Patients who have undergone abdominal surgery are at increased risk of developing adhesions
and requiring emergency surgery for intestinal obstruction. Despite several decades of extensive investigation of
Table 6.3 Studies investigating mesothelial plasticity
Inhibition of
Stimulation
with
Study Year Journal Subject Pathology
Nasreen
etal.
Strippoli
etal.
Li etal. 2013 PNAS Murine Hepatic brosis Yes Yes Yes [115]
Sandoval
etal.
Karki
etal.
Loureiro
etal.
Sources: Burke, J.P. etal., Br J Surg, 97(7), 1126, 2010; Burke, J.P. etal., Br J Surg, 97(6), 892, 2010; Burke, J.P. etal., Br J Surg, 96(5), 541,
Note: MMT, mesothelial to mesenchymal transformation; TGF-β, transforming growth factor beta.
2009 Am J
Physiol
Lung Cell
Physiol
2008 Dis Models
Mech
2013 J Pathol Human +
2014 FASEB Human +
2013 PLOS ONE Human +
2009; Sahebally, S.M. etal., Br J Surg, 100(12), 1549, 2013; diZerega, G., Peritoneal Surgery, Springer, New York, 1999; Garriga, V.
etal., Radiographics, 29(7), 2017, 2009.
Human Idiopathic
pulmonary
brosis
Human Peritoneal
brosis
Peritoneal
murine
murine
murine
carcinomatosis
Idiopathic
pulmonary
brosis
Peritoneal
brosis
TGF-β1
Yes No Ye s [117]
Yes No Ye s [119]
Yes Yes Yes [118]
Yes No Ye s [114]
Yes Tamoxifen Yes [116]
MMT with
anti-
TGF-β1?
Phenotpyic
change
observed? Reference
Mesothelial secretion and absorption of peritoneal uid 75
(c) (d)
adhesion formation, eective preventative measures are
lacking. is relates to the fact that we continue to have a
poor understanding of the coordinated mesothelial and
mesenchymal activities that occur during adhesion formation [127,134]. Marked similarities occur between mesenteric mesothelium, submesothelial connective tissue, Toldt’s
fascia, and adhesion formation. ese point to a cellular and
molecular overlap and will be discussed in greater detail in
the following chapter.
MESOTHELIAL SECRETION AND
ABSORPTION OF PERITONEAL FLUID
Mesenteric mesothelium produces and absorbs peritoneal
uid at varying rates. In the male, 5 mL peritoneal uid
is produced daily. In females, this volume varies with the
menstrual cycle and ranges from 5 mL in the luteal phase
to 18 mL during menstruation [127,135,136]. Accumulation
of peritoneal uid increases dramatically in an array of
Mesothelial cells, green =cytokeratin,
blue=Hoechst (DNA stain)
(a) (b)
Fibroblast; red, vimentin; green, collagen I; green
overshadows, Hoechst blue at nucleus
Fibrocytes, green=collagen I, red/pink=CD45
shown as pink due to presence of Hoechst,
CD45 located around the nuclear membrane
Myofibroblast, red=alpha smooth muscle actin,
blue=Hoechst (DNA)
Figure 6.5 Panel demonstrating different mesenchymal cell types generated following the exvivo culture of mesenteric
mesothelium. (a) Mesothelial cells approximately 24 hours following culture setup. (b) Fibrocytes. (c) Fibroblasts.
(d)Myobroblasts. (Continued)
76 Mesenteric physiology
(e) (f)
Myofibroblast with cytokeratin remnants,
red=alpha smooth muscle actin, blue=Hoechst,
green=cytokeratin
Figure 6.5 (Continued) Panel demonstrating different mesenchymal cell types generated following the exvivo culture of
mesenteric mesothelium. (e) and (f) Myobroblasts with intracytoplasmic cytokeratin.
pathologic conditions including cirrhosis, ovarian bromas
(Meigs’ syndrome), bowel cancer, peritoneal carcinomatosis, visceral inammation, ovarian torsion, and pedunculated uterine leiomyomata (due to mechanical impairment
of venous outow) [137–139].
Peritoneal uid secretion increases dramatically during
postsurgical repair or inammation [127]. Just as secretion increases, so too does absorption and uid volumes
(reected in abdominal drain outputs) then decrease. ese
reect changes in mesothelial functionality as the latter
must rst proliferate and reperitonealize to cover surfaces
not ordinarily exposed (i.e., mesentery, fascia, abdominal
wall, retroperitoneum).
Numerous cell types occur in peritoneal uid.
Macrophages and mesothelial cells account for 36% of the
cellular population, while lymphocytes and polymorphonuclear cells make up 18% and 7%, respectively. Peritoneal
dialysis exploits the absorptive capacity of mesenteric mesothelia. is capacity is considerable given the volume produced daily [127].
Transfected fibroblast with SV40 T-antigen,
red=TRITC phalloidin that stains actin in any cell,
green=antibody to SV40 T-antigen, nuclear stain
lymphatic spread from the colon was elegantly demonstrated by Boni etal. ey separately injected a colon cancer
cell line into the antimesenteric border and mesenteric border of a rat colon [141]. ey then investigated the pattern of
lymphatic spread. In rats injected into the anti-mesenteric
border, mesenteric nodal spread was limited to a minority
of animals, while carcinomatosis occurred in the majority. Carcinomatosis is characterized by a diuse peritoneal
studding with individual tumor deposits. In advanced carcinomatosis, the deposits coalesce and become matted. In rats
injected into the mesenteric margin, nodal spread occurred
in the majority of animals and carcinomatosis wasinfrequent. eir observations can be explained by the lymphatic
contiguity between the mesocolon and the intestine.
e observations of Boni et al., taken in conjunction
with clinical observations in gastric and ovarian cancer,
may have additional implications. In gastric, ovarian, and
sometimes appendiceal cancer, the pattern of spread may
be peritoneal (leading to carcinomatosis) rather than nodal.
Although carcinomatosis is generally attributed to dispersion in peritoneal uid, it could also be explained by spread
MESOTHELIAL LYMPHATICS
through lymphatic channels in submesothelial connective
tissue. e development of nodal spread, and the relative
As previously mentioned (see Chapter 4), a connective tissue
continuity occurs between the intestine and the connective tissue lattice within the mesentery [9,10]. A lymphatic
lack of overlap between carcinomatosis and nodal patterns
of lymphatic spread, may be explained by alterative lymphatic systems within the mesentery.
network is housed within this lattice (Figures 6.6 and 6.7).
Inaddition, a lymphatic continuity occurs between intes-
GREATER OMENTUM
tine and adjacent mesentery [140].
Although the concept of continuity may be taken for
granted, it is extremely important in the context of the
distribution of cellular or molecular entities. Mesenteric
According to current embryologic theories, the greater
omentum is related to the mesentery in so far as both derive
from the same developmental forerunner. Based on this,
Right
Mesenteric organ
mesentery
(b)
(c)
mesocolon
Greater omentum 77
Small bowel
mesentery
(a)
Surface
mesothelium
Submesothelium
connective tissue
Lymphatic network
Connective
tissue of
Connective
tissue
lattice
within the
connective tissue
Figure 6.6 2.5D snapshots of 3D digital sculptures. (a) The ileocecal junction where the small intestinal mesentery
continues as the right mesocolon. (b) The connective tissue lattice and surface mesothelium contained in the mesentery.
Adipocytes have been conceptually removed to illustrate the nature of the lattice. Ordinarily the compartments generated
in the lattice are packed with adipocytes. (c) Mesenteric lymphatics with connective tissue removed.