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Abstract and Figures

Systematic study of the mesentery is now possible because of clarification of its structure. Although this area of science is in an early phase, important advances have already been made and opportunities uncovered. For example, distinctive anatomical and functional features have been revealed that justify designation of the mesentery as an organ. Accordingly, the mesentery should be subjected to the same investigatory focus that is applied to other organs and systems. In this Review, we summarise the findings of scientific investigations of the mesentery so far and explore its role in human disease. We aim to provide a platform from which to direct future scientific investigation of the human mesentery in health and disease.
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238 Vol 1 November 2016
The mesentery: structure, function, and role in disease
J Calvin Co? ey, D Peter O’Leary
Systematic study of the mesentery is now possible because of clari? cation of its structure. Although this area of
science is in an early phase, important advances have already been made and opportunities uncovered. For example,
distinctive anatomical and functional features have been revealed that justify designation of the mesentery as an
organ. Accordingly, the mesentery should be subjected to the same investigatory focus that is applied to other organs
and systems. In this Review, we summarise the ? ndings of scienti? c investigations of the mesentery so far and
explore its role in human disease. We aim to provide a platform from which to direct future scienti? c investigation of
the human mesentery in health and disease.
One of the earliest depictions of the mesentery associated
with the small bowel and colon was generated by
Leonardo Da Vinci.1,2 The Da Vinci mesentery was con-
tinuous and appeared to converge centrally. Over the
following four centuries, medical illustrators, surgeons,
and physicians drew the mesentery as it appeared in situ,
suggesting contiguity. In 1879, Toldt3 identi? ed a
mesentery associated with the ascending and descending
colon and showed that, although these structures were
? attened against the posterior abdominal wall, they
remained separate from it. He did not, however, combine
these ? ndings to identify mesenteric contiguity.4 Toldt’s
? ndings were highly accurate, but were summarily
ignored during the 20th century.5 Instead, the 1885
? ndings of Treves6 were preferred. He concluded that the
ascending and descending colon do not normally have an
associated mesentery.7 The resulting depiction in most
anatomical, embryological, surgical, and radiological
literature of the next century was a fragmented
mesentery, present only at the small-intestine, transverse
colon, and sigmoid colon.8–10 Indeed, some publications
continue to depict the presence of a right or left
mesocolon as being anomalous.11–18
The mesentery associated with the small intestine
and colon is now regarded as contiguous (? gure 1).2
It emerges from the superior mesenteric root region and
fans out to span the intestine from duodenum to
rectum; however, the continuity can be seen only when
the mesentery is exposed in a certain way. Dividing the
peritoneum provides access to a plane formed by the
mesentery and underlying fascia. When peeled away
from the fascia, the mesentery emerges as a discrete
entity (? gure 1). Repeating this process from duodenum
to rectum reveals the entirety of the mesentery. Of note,
this approach has been used in colorectal resection for
many years to permit safe intestinal resection.
Mesenteric contiguity was ? rst demonstrated in an
observational cohort study of patients undergoing total
mesocolic excision,19 in which the entire mesocolon is
detached from the posterior abdominal wall. Similar
observations were made in a cadaveric study of this
approach, by the same authors.20 Mesenteric contiguity
is also apparent in embryological variants, such as
non-rotation or malrotation, situs inversus, and mesenteric
atresia. Mesenteric, peritoneal, and fascial contiguity were
con? rmed with datasets available in the Visible Human
Project,2,21 which provides cross-sectional photographs of
human anatomy without alteration and in full colour, with
corresponding axial CT images. From these datasets, the
mesentery was identi? ed in full, enabling develop ment of
a radiological atlas of the normal contiguous mesentery
against which abnormalities can be compared.22
Clari? cation of the mesenteric anatomy was used to
derive a surgical nomenclature applicable to all forms of
resectional colorectal surgery.22–26 This terminology is
increasingly being used worldwide to describe the
individual steps involved in mobilising and resecting the
intestine.27–32 The adoption of a universal nomenclature has
notable bene? ts, including standardisation of the resection
process, permitting valid comparisons in clinical trials.
Such comparisons have so far been lacking, and related
surgical literature is dominated by trials comparing types
of mesenteric-based surgery (total mesorectal excision,
complete mesocolic excision) with ill-de? ned approaches
collectively referred to as “conventional” surgery.33
A standardised nomenclature may also be repeatedly used
Lancet Gastroenterol Hepatol
2016; 1: 238–47
Graduate Entry Medical School,
4i Centre for Interventions in
Infection, Inflammation and
Immunity, University Hospital
Limerick, University of
Limerick, Limerick, Ireland
(Prof J C Coffey FRCSI,
D P O’Leary PhD)
Correspondence to:
Prof J Calvin Coffey, Graduate
Entry Medical School, 4i Centre
for Interventions in Infection,
Inflammation and Immunity,
University Hospital Limerick,
Limerick, Ireland
Transverse mesocolon
Small intestinal mesentery
Right mesocolon
Figure 1: Digital representation of the small and large intestines and
associated mesentery Vol 1 November 2016
in the educational setting. Thus, the colorectal community
can now be systematic in per forming and teaching
intestinomesenteric mobilisation and resection. The most
relevant implication of mesenteric contiguity was that it
permitted, for the ? rst time, systematic investigation of the
mesentery and, by de? nition, its related structures.2
Previously, mesenteric research had been done under
several unrelated headings, but the discovery allowed
seemingly disparate ? ndings to be brought together under
the heading of mesenteric science.
Exciting opportunities for investigation are now
emerging in relation to the role of the mesentery in health
and disease.34 Mesenteric events are important in the
pathobiology of diverse abdominal and non-abdominal
disorders, including colorectal cancer, in? am matory
bowel disease, diverticular disease, cardiovascular
disease, diabetes, obesity, and metabolic syndrome.35–37
We therefore summarise the scienti? c ? ndings of the
mesentery’s role in health and disease and explore the
directions future investigations might take.
Anatomy and embryology
The mesentery distal to the duodenojejunal ? exure is a
contiguous and extraretroperitoneal organ (? gures 1–3).23,38
It is compactly folded in a spiral conformation within the
peritoneal cavity. The small intestinal mesentery is
mobile, whereas the right mesocolic region is ? attened
against the posterior abdominal wall. It then changes
conformation to continue as the transverse mesocolon,
with another change in conformation at the splenic
? exure to continue distally as the left mesocolon (? gure 1).
The left mesocolon and medial region of the mesosigmoid
are ? attened against the posterior abdominal wall
(? gure 4),2 whereas the intestinal margin of the
mesosigmoid is mobile and elongates in tandem with the
sigmoid colon. These two regions of the mesosigmoid
converge distally at the pelvic brim and extend into the
pelvis as the mesorectum (? gure 4), which anatomically
terminates in the distal pelvis.
The shape of the mesentery is remarkable. It emerges
from the “root region” (as named by Treves), which
corresponds to the attachment of the superior mesenteric
artery to the aorta.2,6 The mesentery distal to the
duodenojejunal ? exure can be viewed as similar to a
handheld fan, with the central pivot point corresponding
to the origin of the middle colic artery from the superior
mesenteric artery.20 From this point, the mesentery
extends radially up to the intestinal margin. It elongates
along with the intestine and folds repeatedly, making the
intestinal margin extremely long. The body of the fan
consists of regions in the following sequence:
small-intestinal mesentery; right, transverse, and left
meso colon; mesosigmoid; and mesorectum. The right
and left mesocolic regions and the medial mesosigmoid
region curve onto and are ? attened against the posterior
abdominal wall. They are held attached in these
regions by Toldt’s fascia and the peritoneal re? ection
(? gures 24).20,21 Intervening regions of the fan (ie, the
small-intestinal mesentery, transverse, and mesosigmoid)
are contiguous with attached regions but are mobile and
not ? attened against the posterior abdominal wall.
Suspension and mesenteric attachment prevent the
intestine from collapsing into the pelvis.
It is feasible that the intestine and mesentery are
contiguous from the diaphragm to the pelvic ? oor.20
Accordingly, the meso gastrium and mesoduodenum
(containing the pancreas) are thought to be continuous
with the mesentery of the jejunum, ileum, and colon,
although this alignment needs con? rmation in future
studies. The transverse mesocolon consists of a
Figure 2: Digital representations of peritoneum, mesentery, fascia, and intestine
(A) Peritoneum, mesentery, fascia, and intestine. (B) Mesentery, fascia, and intestine. (C) Mesentery and intestine.
(D) Mesentery.
240 Vol 1 November 2016
con? uence between the mesenteric components of the
hepatic and splenic ? exure and the middle colic
adipovascular pedicle.20 It forms a caudal limit to the
lesser sac. The greater omentum adheres to the cephalad
surface of the transverse mesocolon and partially
obliterates this space.
The latest depiction of the mesentery helps with
understanding of ? exural anatomy (? gure 3). There are
six ? exures: duodenojejunal, ileocaecal, hepatic, splenic,
and those between the descending and sigmoid colon
and the sigmoid and rectum (? gures 3, 4).24 All six have
contiguous intestinal, mesenteric, peritoneal, and fascial
components (? gure 3). This knowledge greatly simpli? es
technical aspects of colorectal surgery in these regions.
Suspension of the mesentery prevents the intestine
collapsing into the pelvis, and is mediated by vascular
connections (ie, the superior and inferior mesenteric
vessels). Suspension is further aided by mesenteric
attachment, that is the apposition or ? attening of
mesenteric regions against the posterior abdominal
wall.20,21 The right and left mesocolon and the medial
mesosigmoid and mesorectum are apposed or attached
to subjacent abdominal wall or surrounding pelvis
(? gure 4). If attachment does not occur, the intestine and
mesentery are suspended at vascular pedicles alone
and thus prone to twisting with vascular occlusion. This
phenomenon occurs in non-rotation or malrotation,
discussed later, and is the commonest cause of death due
to abdominal crises in the ? rst year of life.
Although contiguous, the peritoneal re? ection has
several names, according to the anatomical region:
the peritoneal re? ection, Jackson’s membrane, the
anterior re? ection, the Pouch of Douglas, and the lateral
peritoneal re? ection (? gure 2).24
Toldt’s fascia is also contiguous (? gures 2–4),20,21,24 as
con? rmed by high-magni? cation and high-de? nition
intraoperative imaging during laparoscopic (and in
particular robotic) surgery,20,39 and has various names for
the di? erent regions. Where it surrounds perirenal fat, it
is frequently referred to as Gerota’s fascia. Beneath the
left and right colon it is called Toldt’s fascia.24 At this point
it has been erroneously called the vestigial right and left
mesocolon. Beneath the right and left mesocolon it
is also referred to Toldt’s fascia. Continuing under
the mesosigmoid, into the pelvis, and separating the
mesorectum from the bony pelvis, the fascia is called the
mesorectal fascia. Where the mesorectum terminates
above the pelvic ? oor, a space occurs. Where the fascia
? lls this space, it is termed Waldeyer’s fascia. Given
Toldt’s contributions to this ? eld, we propose that the
entire fascial layer be collectively referred to as Toldt’s
fascia, with the di? erent regions denoted by the region of
associated mesentery (ie, mesosigmoidal, mesorectal,
mesocolon, and mesenteric regions).
The universality of contiguity in adult human beings
indicates that the embryogenesis and development of the
mesentery is one of the most conserved processes in
human embryology. Broadly speaking, the intestine
develops from the endodermal germ layer, whereas the
mesentery derives from the mesodermal germ layer.40
The processes involved in the embryological development
of the mesentery were previously based on classic
anatomical theories that attempted to reconcile
mesenteric regression, fragmentation, and dis con-
tinuity.41,42 These included the sliding and regression
theories,43–45 neither of which gained a foothold in the
mainstream scienti? c literature. According to the
regression theory, the dimensions of the embryological
dorsal mesentery are such that, with relative lack of
further growth, and with future growth of the right and
left colon, their respective mesenteries regress and
Hepatic ?exure
Colic component
Peritoneal component
Fascial component Mesenteric component
Mesenteric component
Fascial component Mesenteric component
Figure 3: Anatomical components of the hepatic ? exure
Snapshots from a digital sculpture showing (A) undisturbed hepatic ? exure, (B) ? exure separated from contiguous
structures highlighting the colic component, (C) view of contiguous mesentery, (D) divided peritoneal component
of ? exure, and (E) fascial component of ? exure. Vol 1 November 2016
become vestigial. According to the sliding theory, as the
right and left colon adopt their ? nal lateral positions they
pull their respective mesenteries with them until these
take up their ? nal location as vestigial mesenteries
posterior to the right or left colon respectively.
With contiguity now revealed, the embryological
develop ment of the mesentery, peritoneal re? ection,
and fascia need to be reappraised. Fortunately, the adult
structure is far simpler than that previously proposed,
and might be more easily explained by mechanical and
cellular events. By reverse engineering its develop ment
with the adult shape as a starting point, mesenteric
embryology can be simpli? ed into a set number of key
processes: suspension at points of vascular connectivity;
di? erential elongation of regions of the intestine and
mesentery with a resultant counter-clockwise rotation
of both, mesenteric ? attening against the posterior
abdominal wall, and development of Toldt’s fascia and
the peritoneal membrane to maintain attachment in
this conformation. Under standing of the anatomy of the
entire mesentery provides new anatomical endpoints to
which embryologists should work to further characterise
the development of the mesentery and associated
The fundamental histological elements of the mesentery
are the surface mesothelium, the connective tissue
lattice, and adipocyte populations housed in the inter-
stices of the lattice. So far, little is known about the
cellular components of these elements.
In regions where the mesentery is ? attened against or
attached to the posterior abdominal wall, Toldt’s fascia is
present in between.23 Although the fascia contains
minute vessels and lymphatics, the sites of origin and
termination of these have yet to be con? rmed.
Histological and scanning electron microscopic analyses
in this region have shown that Toldt’s fascia is a true
fascia in the anatomical sense.21 It is interposed between
the visceral peritoneum of the overlying mesocolon and
the parietal peritoneum of the retroperitoneum. In the
past, the terms visceral and parietal fascia were
incorrectly applied to these mesothelial layers.46 As they
are epithelial and not mesenchymal, they are not fascia
in the anatomical and surgical sense. Thus, the terms
visceral and parietal peritoneum should be used to
reference these mesothelial layers.47
At the intersection between the intestine and the
mesentery, the mesenteric mesothelium continues onto
the intestine and contributes to the cellular component of
the outer layer, the serosa. Additionally, the connective
tissue of the mesentery contributes to, and is contiguous
with, that of the serosa.48 From the serosa, connective
tissue septations extend into underlying muscle and
submucosa, meaning that the mesenteric and intestinal
connective tissues are contiguous. Classic histological
studies from Toldt3–5 pictorially hinted at this arrangement,
which is a remarkable achievement given the limit of
imaging resolution possible at the time.
For many years, the interface between the body and
intestine (or environment) was postulated to be
represented by lymphovascular and neurological
elements embedded in the submucosa. Little, if any,
reference was made to the intersection between the
mesentery and intestine. However, it is now recognised
that this histological overlap is the true intestinal hilum
(ie, where blood vessels enter or leave) and spans the
intestine from duodenum to rectum.21
The anatomical distinctiveness of the mesentery is
mirrored by unique functions. The mesentery suspends
much of the intestines from the posterior abdominal
Apposed/attached mesosigmoid
Rectosigmoid junction
Rectum Rectum
Proximal mesorectum Mid-mesorectum
Figure 4: Axial (craniocaudal) views of mesosigmoid and mesorectum
(A) Upper mesosigmoidal, (B) mid-sigmoidal, (C) distal mesosigmoidal, (D) rectosigmoidal, (E) proximal, and
(F) mid-mesorectal levels.
242 Vol 1 November 2016
wall,19 preventing it from collapsing into the pelvis when
standing upright. Intestinal transit would probably be
slowed or possibly even cease without this attachment.
Mesenteric attachment facilitates suspension of the
colon,20 allowing it to adopt a spiral conformation. It is
feasible that mesenteric suspension and attachment
were important developments that facilitated vertical
ambulation in Homo sapiens, although examination of
mesenteric attachment in lower-order species is needed
to con? rm or refute this suggestion.
The mesentery is interposed between the intestines
and the body,20 making it is optimally positioned to
sample intestinal (ie, environmental) cues and mediate
local responses, systemic responses, or both. Mesenteric
nodes sample bacterial components derived from the
adjacent intestine49 and regulate migration of B cells,
T cells, natural killer cells, and dendritic cells to nearby
intestinal mucosa.50 However, owing to the sporadic way
in which mesenteric-based feedback mechanisms have
so far been identi? ed, they are not fully understood.
Additionally, many of the ? ndings were made in animal
studies, and how they translate to the human context
needs to be con? rmed.
Mesenteric production of C-reactive protein is an
important determinant of systemic concentrations.
C-reactive protein regulates glycaemic and lipid meta-
bolism. Data suggest increasingly that mesenteric events
contribute to the regulation of systemic ? brinolytic,
in? ammatory, and coagulation cascades.51–53
The mesenteric mesothelium is the single largest
expanse of mesothelium in the human body. It has
transformative capacities that might be relevant to tissue
repair (ie, after surgery) and various disorders (ie, hernia
and adhesion formation).54 The mesenteric mesothelium
is a stem cell niche that has undergone remarkably little
investigation. Understanding of the enteromesenteric
component of the peripheral nervous system is also
de? cient.55–57 No studies have comprehensively charac-
terised the mesenteric component of the peripheral
nervous system in adults. Postganglionic nerves leave
the three major abdominal ganglia to reach the intestine,
but their trajectory is poorly characterised. Given the
relevance of the mesentery to intestinal function and
overall homoeostasis, neurological studies of the
mesenteric component of the enteric nervous system
should be given increased emphasis.
Role in disease
Improved understanding of the normal mesenteric
shape enables identi? cation of mesenteric abnor-
malities,20 which in turn permits investigation of the
relation between mesenteric abnormalities (position
and nature) and disease. The multilevel contiguity
between the mesentery and adjacent organs provides a
structural platform to maintain homoeostasis, but also
provides a means for disease spread. A mesenteric-
based approach to disease classi? cation therefore has
broad applicability. We provide a brief description of its
application to several common dis orders, including
primary58–63 and secondary64–69 mesen teric abnormalities
Primary mesenteropathies
Primary mesenteropathies arise from the mesentery
itself, owing to its intrinsic properties. Examples are
volvulus, non-rotation, superior mesenteric artery
thrombosis, sclerosing mesenteritis (of which there are
several subtypes), and mesenteric cysts.58–63
As detailed in the section on anatomy, the intestinal
margin of the mesentery elongates in tandem with the
intestine. This property predisposes to volvulus (twisting
or torsion) of the mesentery and the attached intestine.
Volvulus is prevented by ? attening and attachment of
alternating regions of the mesentery to the posterior
abdominal wall. For example, attachment of the right
mesocolon reduces the risk at the ileocaecal junction.
Volvulus can occur anywhere that mesenteric attachment
is incomplete or inadequate. The medial region of the
mesosigmoid is attached, whereas the lateral region is
mobile (? gure 4). If the di? erential in length between the
attached and mobile regions is su? cient, a volvulus
occurs. Rarely, volvulus develops in the transverse
mesocolon and colon for the same reason.
Non-rotation (also known as malrotation)
If the mesentery does not rotate as normal during
embryological develop ment, mesenteric attachment
does not occur and the adult conformation is abnormal
(? gure 5). Instead, the intestine and mesentery are
suspended at vascular pedicles alone, and the mesentery
twists around these points of connection. The result is a
catastrophic volvulus of the mesentery and intestine.
Non-rotation (malrotation) is the most common cause of
fatality due to abdominal crises in the ? rst year of life.
Internal herniation related to mesenteric defects
Mesenteric defects or gaps can act as routes for intestinal
herniation. This disorder might arise postoperatively
(eg, after intestinal resection), or spontaneously (eg, due
to mesenteric atresia). After intestinal resection, the
resultant mesenteric defect should be closed if it is
narrow and risk of herniation is high.
Vascular mesenteropathies
Vascular mesenteropathies are among the most common
mesenteric disorders, and include acute occlusion of
the superior mesenteric artery and thrombosis of the
superior mesenteric vein.58,59 The major vessels of the
mesentery are the superior and inferior mesenteric
arteries and veins. The manner in which these subdivide
or branch is variable. For example, a right colic artery
arising directly from the middle colic artery is seen Vol 1 November 2016
in only 25% of the general population.70 Vascular
mesenteropathies can be catastrophic since they might
lead to rapid and extensive necrosis of the small intestine.
Occlusion of the superior mesenteric artery can be
embolic or can arise as a result of thrombus formation
on an atherosclerotic plaque.
Mesenteric cysts
Cysts on the mesentery are uncommon and arise
after mesenteric mesothelial proliferation (? gure 5).
Mesenteric cysts can be asymptomatic, although sudden
expansion secondary to haemorrhage can lead to severe
abdominal pain.71,72
Cellular mesenteropathies
The pathologies discussed earlier have a mechanical
basis. Increasing data point to the occurrence of cellular
mesenteropathies.73 The concept of cellular me sentero-
pathies is supported by ? ndings in sclerosing mesenteritis
and adhesion formation.74 With increasing investigation
of the histological basis of the mesentery in health and
disease, further examples of this disease subtype are
likely to emerge.
Mesenteric mesothelium can undergo mesenchymal
transformation, contributing to local mesenchymal
popu lations and activities. Abnormal mesothelial pro-
liferation is driven by chronic in? ammation, and is a
feature of mesenteric lipodystrophy, mesenteric panni-
culitis, and IgG4-related sclerosing mesenteritis.75–77
Synchronous mesothelial and mesenchymal proliferation
occur when adhesions form after surgery. It is feasible
that mesothelial proliferation provides a cellular basis to
the mesothelial (ie, hernia) sac. The hernia sac is an
important anatomical component of most forms of
abdominal hernia.
Secondary mesenteropathies
Secondary mesenteropathies arise from extrinsic sources
and might occur due to direct (ie, contiguous) or systemic
spread of a disease process. Examples include mesenteric
involvement in intestinal malignancy or in? ammation
(ie, diverticular disease).64–69
Intestinal malignancy
Intestinal malignancy can lead to various secondary
e? ects in the adjacent mesentery. Lymphatic contiguity
between the mesentery and intestine provides a means
for disease spread. Lymphatic spread to mesenteric
nodes is thought to be an important mechanism for the
systemic spread of intestinal tumours.78 Additionally,
intestinal tumours might invade or perforate into the
contiguous or nearby mesentery.
Crohn’s disease
Mesenteric fat wrapping and thickening are prototypical
of Crohn’s disease. The classic view of Crohn’s disease is
that it is as an intestinal disorder (? gure 5),79 making
associated mesenteric abnormalities secondary. However,
some ? ndings suggest that mesenchymal abnormalities
can extend from the mesentery into the subjacent
intestine,80 in which case, Crohn’s disease might be a
primary mesenteropathy. Mesenteric inputs explain the
transmural appearance of Crohn’s disease as well as the
origin of mesenchymal cells responsible for the disease.
Obesity, diabetes, atherosclerosis, and metabolic syndrome
The clinical relevance of the mesentery is not con? ned to
abdominal disease.68,81,82 It is the single greatest con tributor
to visceral adiposity,83 which regulates systemic con cen-
trations of C-reactive protein.49 Dysregulation of systemic
C-reactive protein has an important role in the patho-
biology of obesity, atherosclerosis, diabetes, and metabolic
syndrome.84 Studies should be done to investigate whether
increased mesenteric adiposity is a primary or secondary
pathobiological event in these disorders.
Mesenteric-based diagnostics
Mesenteric diagnostics aim to identify and assess (or stage)
mesenteric abnormalities by non-invasive or minimally
invasive means. However, the mesentery is anatomically
Figure 5: Primary mesenteropathies
(A) Various views of the conformation of the normal mesentery and intestine. (B) Various views of the intestine
and mesentery in non-rotation (ie, malrotation). (C) Mucosal and (D) mesenteric transition zones in a
postoperative resection for Crohn’s disease. (E) Mesenteric cyst seen in a postoperative specimen.
244 Vol 1 November 2016
remote and, at present, can only be assessed by radiological
or surgical means.22,23 Radiological approaches are regarded
as particularly complex due to the concept of mesenteric
discontinuity. Abdominal radiologists continue to face
challenges when they attempt to reconcile the radiological
appearance of the mesentery with classic appraisals
of mesenteric anatomy. In the 1980s, Oliphant and
Berne85 proposed mesenteric contiguity with “a posterior
abdominal core”, and Dodds and colleagues86 suggested
that the entire mesentery was extra retro peritoneal. Their
hypotheses resonate with current under standing of
mesenteric anatomy. Nevertheless, most updates on
mesenteric and peritoneal radiology still lead o? with the
assertion that it remains di? cult.
Clari? cation of mesenteric and peritoneal structure has
provided a basis on which to examine the radiological
appearance of the mesentery systematically, in normality
and disease. Advances in abdominal CT and MRI mean
that the ? exural and non-? exural regions of the mesentery
can be reproducibly identi? ed in adults with normal
anatomy, embryological variations, and abdominal
diseases.23 Although gaining traction, these advances
have yet to be included in educational programmes.
Endoscopic visualisation can be used to map the
mesentery and could facilitate transintestinal biopsy
in a similar way to transrectal prostate biopsy.
Transintestinal mesenteric biopsy would provide
diagnostic data on secondary mesenteric disorders
(eg, cardiovascular disease, diabetes, obesity, metabolic
syndrome, and Crohn’s disease). Endoscopic mapping
during colonoscopy can provide endoscopists, on a
patient-by-patient basis, with a trajectory along which
the large intestine may be traversed with minimum
discomfort to the patient.87 By combining longi tudinal
and axial positions, polyp location might be pinpointed
to guide future investigation or resection.
Mesenteric-based therapeutic strategies
The anatomical remoteness of the mesentery is such that
surgery is the only means of altering it. Surgical
manipulation of the mesentery is well developed in so far
as surgeons have long recognised the importance of
removing it as part of intestinal resection. Jamieson and
Dobson88 showed as early as 1909 the importance of
removing the lymphatic drainage of the colon during
resection for colon cancer. Miles89 showed similar
bene? ts in treatment of rectal cancer. In 1982, Heald and
colleagues90 found that removing an intact mesorectal
package was bene? cial in surgical management of the
rectum. Likewise, Hohenberger and colleagues91 showed
the importance of removing an intact mesocolic package
in resection of colon cancer.
The detachment and disconnection of an intact
mesenteric package by surgeons for many years is
striking because it was at odds with the reference surgical
and non-surgical texts which stated that persistence of a
right or left mesocolon was anomalous.9,10 Identi? cation
and con? rmation of mesenteric contiguity led to
resolution of disparity between surgical approaches17 and
provided a common anatomical basis for the concepts of
total mesorectal excision, total mesocolic excision, and
complete mesocolic excision. Indeed, it provides an
anatomical foundation for good-quality resectional
surgery from the duodenum to rectum.
Clari? cation of mesenteric anatomy will have many
bene? ts for colorectal surgery. Surgery can be more
systematised,28 which in turn will allow tailoring of
educational information and lead to standardisation of
the surgical process. Systematisation will also facilitate
rigorously controlled randomised trials, which have long
been called for but have not so far been possible.
The range of diseases that can be treated with
mesenteric strategies is increasing.92,93 Recommendations
that the mesentery should be included in resections for
Crohn’s disease have been largely ignored due to the
dangers (eg, extensive haemorrhage) associated with
division of the Crohn’s mesentery. Reoperation rates
remain as high as 40% after resection for Crohn’s
disease.94,95 However, data suggest that margin positivity
and reoperation rates can be substantially reduced if
resection is guided by mesenteric-based strategies.34
Mesenteric pharmacology is poorly developed. Few
data are available on drug pharmacokinetics or
pharmacodynamics within the mesentery. Early ? ndings
in mouse studies suggest that in? iximab can alter the
mesenteric cytokine environment.96 With increasing
recognition of the central functionality of the mesentery,
the number of studies is likely to expand.
Conclusions and future directions
Clari? cation of mesenteric structure has raised many
questions, but has simultaneously provided a platform
from which to direct future investigations across natural
and applied sciences. Various anatomical and other
features of the mesentery need to be detailed. Contiguity
of lymphatic, neurological, vascular, and connective
tissue means that the mesentery occupies a central
position.21,97 Whether the mesen tery should be viewed as
part of the intestinal, vascular, endocrine, cardiovascular,
or immunological systems is so far unclear, as it has
important roles in them all. Its e? ects are being
investigated at haematological, immunological, endo-
crine, metabolic, and other levels.98–101 Many, but not all,
organs have a distinct functional unit. The functional
unit of the mesentery is unknown, and whether a
distinctive cell type is primarily responsible for its
functionality should be investigated.
Several anatomical questions also remain unanswered.
For example, although early data suggest that the
mesentery proximal to the duodenojejunal ? exure is
contiguous with it, this is still unclear. If this is the case,
discovering the mesenteric factors that drive development
of the pancreas in one mesenteric region and not in
another will be of great interest. If the proximal mesentery Vol 1 November 2016
is contiguous, the anatomical correlate of the meso-
oesophagus could also be investi gated. The relation of the
greater omentum to the remainder of the mesentery
should be re-examined.
Mesenteric mesothelial plasticity and transformation
contribute to several disorders, including adhesion and
hernia formation. Focusing research on the molecular
and cellular cornerstones of mesothelial plasticity might
reveal that related events, such as postoperative adhesion
or hernia sac formation, can be altered. The multilevel
contiguity of mesentery and adjacent structures is being
investigated as a route for the spread of disease. Connective
tissue contiguity could explain the develop ment of
musculoskeletal, ocular, and cutaneous abnormalities in
intestinal diseases, such as ulcerative colitis and Crohn’s
disease, and might also account for so far unexplained
patterns of pathogen and disease spread.
Continued development of radiological and endoscopic
mesenteric diagnostics will improve the staging of
abdominal diseases by non-invasive and minimally
invasive means. Endoscopic mesenteric sampling aims
to provide clinically relevant data in an array of abdominal
and non-abdominal disorders and will be addressed in
studies.34,87 It is anticipated that these data will culminate
in the development of non-invasive mesenteric-based
therapies (ie, mesenteric pharmacotherapeutics), which
might obviate surgical intervention. Mesenteric pharma-
cology remains poorly developed, partly due to the
relative inaccessibility of the mesentery, but mainly due
to little investigation. Understanding of drug activities
within the mesentery and mesenteric pharmacokinetics
and dynamics is needed.
In summary, advances in understanding of the mesen-
tery now enable a rigorous and scienti? c study of it.
Accordingly, bene? ts to gastro enterology are anticipated
by improved diagnostics and an expansion of therapeutics
in general. Bene? ts to radiological appraisal of the
abdomen will be achieved by increased accuracy in the
interpretation of abdominal disease. Pathology will bene? t
from enahnced comprehensive understanding in an array
of abdominal and non-abdominal conditions. In surgery,
it is expected that surgical technique, standardisation of
the craft component of abdominal surgery, and its future
scienti? c investigation will all be improved.
JCC conceived the idea of the review on the basis of ? ndings reported by
him and his group. The manuscript was written by JCC and critically
reviewed and edited by DPO. The literature review was done by JCC and
DPO and the review bibliography was populated by DPO.
Declaration of interests
We declare no competing interests.
We thank Dara Walsh, University of Limerick, Limerick, Ireland for
generation of the ? gures.
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... Indeed, the gut microbiota is believed to be a driving factor for inflammation and the development of intestinal lesions, because the surgical diversion of the fecal stream has been shown to induce remission [7][8][9][10]. Mesenteric and intestinal disease manifestations are tightly coupled in CD and, in this context, some authors have recently claimed that the mesentery is a contiguous organ that may play an important role in immunological processes due to its anatomical position in the intestinal tract [11][12][13][14]. Hypertrophy of the mesenteric fat adjacent to the inflamed regions of the intestine, so-called "creeping fat (CF)" is a hallmark of CD and seems to be directly related to disease activity [15,16]. ...
... Hypertrophy of the mesenteric fat adjacent to the inflamed regions of the intestine, so-called "creeping fat (CF)" is a hallmark of CD and seems to be directly related to disease activity [15,16]. Indeed, it has been recently described that reoperation rates among patients with CD decrease dramatically, from 27% to 2.7%, when the mesentery is included during intestinal resection [13]. Mesenteric adipose tissue (AT) expansion in CD is mainly dependent on adipocyte hyperplasia, which occurs via recruitment and differentiation of AT precursors termed AT-derived stem cells (ASCs) [17,18]. ...
... Remarkably, PCoA of the microbiome between CF-VAT and MES-VAT of patients with active CD revealed a similar pattern of clustering, indicating no differences in the microbiome between the fat depots. These findings are in agreement with the concept that considers the mesentery as a continuous organ [13,42,43]. Accordingly, CF-VAT and MES-VAT might serve as a bacterial reservoir. ...
Full-text available
Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.
... From the clinical perspective, surgeons respect the intention-to-treat principle which entails removal of all tumor spreading pathways at surgery [10]. In bowel cancer surgery, the fatty tissue connecting the bowel to the body (the mesentery) contains all of these pathways together with vital blood vessels, which are mostly concealed by the thickness of the fat [11]. This visual obstacle is the main reason why most of the compromises in quality of surgery are made, due to higher risks for bleedings and other complications [12]. ...
Full-text available
Purpose: Mixed reality (MR) is being evaluated as a visual tool for surgical navigation. Current literature presents unclear results on intraoperative accuracy using the Microsoft HoloLens 1?. This study aims to assess the impact of the surgeon's sightline in an inside-out marker-based MR navigation system for open surgery. Methods: Surgeons at Akershus University Hospital tested this system. A custom-made phantom was used, containing 18 wire target crosses within its inner walls. A CT scan was obtained in order to segment all wire targets into a single 3D-model (hologram). An in-house software application (CTrue), developed for the Microsoft HoloLens 1, uploaded 3D-models and automatically registered the 3D-model with the phantom. Based on the surgeon's sightline while registering and targeting (free sightline /F/or a strictly perpendicular sightline /P/), 4 scenarios were developed (FF-PF-FP-PP). Target error distance (TED) was obtained in three different working axes-(XYZ). Results: Six surgeons (5 males, age 29-62) were enrolled. A total of 864 measurements were collected in 4 scenarios, twice. Scenario PP showed the smallest TED in XYZ-axes mean = 2.98 mm ± SD 1.33; 2.28 mm ± SD 1.45; 2.78 mm ± SD 1.91, respectively. Scenario FF showed the largest TED in XYZ-axes with mean = 10.03 mm ± SD 3.19; 6.36 mm ± SD 3.36; 16.11 mm ± SD 8.91, respectively. Multiple comparison tests, grouped in scenarios and axes, showed that the majority of scenario comparisons had significantly different TED values (p < 0.05). Y-axis always presented the smallest TED regardless of scenario tested. Conclusion: A strictly perpendicular working sightline in relation to the 3D-model achieves the best accuracy results. Shortcomings in this technology, as an intraoperative visual cue, can be overcome by sightline correction. Incidentally, this is the preferred working angle for open surgery.
... The spleen is located under the ribcage and above the stomach in the left upper quadrant of the abdomen [4]. A spleen is soft and generally looks purple. ...
... This site also offers advantages when considering downstream surgical applications and techniques including a procedure we have termed the "Tie In," in which the tHIO can be put into continuity with the host gut [6]. Importantly, the mesentery shares a blood supply with the intestine, and is thought to contribute to intestinal function, including peristalsis, immune function, and tissue repair [7]. While our previous studies have demonstrated that the mesentery is a viable alternative site for HIO transplantation, a direct comparison between the two transplantation sites has not been performed [8]. ...
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Our group has developed two transplantation models for the engraftment of Human Intestinal Organoids (HIOs): the renal subcapsular space (RSS) and the mesentery each with specific benefits for study. While engraftment at both sites generates laminated intestinal structures, a direct comparison between models has not yet been performed. Embryonic stem cells were differentiated into HIOs, as previously described. HIOs from the same batch were transplanted on the same day into either the RSS or mesentery. 10 weeks were allowed for engraftment and differentiation, at which time they were harvested and assessed. Metrics for comparison included: mortality, engraftment rate, gross size, number and grade of lumens, and expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism. Mortality was significantly increased when undergoing mesentery transplantation, however engraftment was significantly higher. Graft sizes were similar between groups. Morp顺心彩票tric parameters were similar between groups, however m-tHIOs presented with significantly fewer lumens than k-tHIO. Transcript and protein level expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism were similar between groups. Transplantation into both sites yields viable tissue of similar quality based on our assessments with enhanced engraftment and a dominant lumen for uniform study benefiting the mesenteric site and survival benefiting RSS.
... Keywords were further complemented and translated into free-text search terms. Then, a 'comprehensive pearl growing' [14] method using 16 known and topic-relevant studies [3,4,8,[15][16][17][18][19][20][21][22][23][24][25][26][27][28] as 'pearls' was utilized. These studies were explored by title in MEDLINE and Embase to establish the freetext search terms and indexed subject headings. ...
Objectives Recurrence after surgery for Crohn’s disease is common. Anastomotic configuration may influence recurrence and the mesentery may be key. Recently the Kono‐S anastomosis and radical mesenteric excision have been proposed as methods of reducing recurrence. We analysed the literature pertaining to these novel techniques Methods We searched MEDLINE, EMBASE and the Cochrane Library for, and selected, studies evaluating Kono‐S anastomosis and/or radical mesenteric excision in Crohn’s disease. We assessed methodological quality and risk of bias using the Cochrane risk of bias tool for randomized controlled trials and the Joanna Briggs Institute tool for non randomized trials. Narrative synthesis was used to summarise the findings. Results Nine studies (896 patients) were identified. Apart from one RCT with a low risk of bias the overall level of evidence was poor (Grade IV). The Kono‐S anastomosis was associated with a lower incidence of endoscopic and surgical recurrence (0‐3.4% vs 15‐24.4% respectively). Complications, particularly anastomotic leak rate were also lower (1.8% vs 9.3% respectively). Evidence from a single poor quality study suggested that mesenteric excision may reduce surgical recurrence rates when compared mesentery preservation. Discussion Existing literature suggests the Kono‐S anastomosis is safe and may reduce endoscopic and surgical recurrence, but level of evidence is mainly poor. One element of the Kono‐S technique, preservation of the mesentery, may be detrimental to recurrence. Further, higher quality, studies are required to investigate these techniques. Such studies should consider the impact of the degree of mesenteric resection in addition to the anastomosis on disease recurrence.
... Keywords were further complemented and translated into free-text search terms. Then, a 'comprehensive pearl growing' [14] method using 16 known and topic-relevant studies [3,4,8,[15][16][17][18][19][20][21][22][23][24][25][26][27][28] as 'pearls' was utilized. These studies were explored by title in MEDLINE and Embase to establish the freetext search terms and indexed subject headings. ...
Aim Recurrence after surgery for Crohn's disease is common. Anastomotic configuration may influence recurrence and the mesentery may be key. Recently the Kono-S anastomosis and radical mesenteric excision have been proposed as methods of reducing recurrence. We analysed the literature pertaining to these novel techniques. Method We searched MEDLINE, Embase and the Cochrane Library for, and selected, studies evaluating Kono-S anastomosis and/or radical mesenteric excision in Crohn's disease. We assessed methodological quality and risk of bias using the Cochrane risk of bias tool for randomized controlled trials and the Joanna Briggs Institute tool for nonrandomized trials. A narrative synthesis was used to summarize the findings.
... Excess secretion of adipocytokine and macrophage recruitment are features of obesity-related systemic inflammation which lead to lowgrade chronic inflammation [22]. Even in early disease stages visceral fat surrounding diseased non-malignant bowel, such as in Crohn's disease patients, has been shown to contain localized inflammation [23][24][25]. These complex relationships between obesity and inflammation may explain the different associations in patients undergoing cancer surgery and those having surgery for benign conditions. ...
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Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease. Keywords Postoperative complications, obesity, digestive tract, gastrointestinal tract, body mass index, body weight What does this paper add to the literature? There is conflicting evidence regarding the impact of obesity after gastrointestinal surgery. Our international data did not identify obesity as an independent risk factor for postoperative complications. Individual patient meta-analysis with previous data identified obesity to be associated with increased risk in cancer surgery but decreased risk in benign surgery
... The mesentery is considered to be an independent organ, and thus its function and role in various diseases have become issues of intense research interest (23,24). Histological study has confirmed that the epithelial cells and connective tissue of the mesentery are continuous with the intestinal wall (25). ...
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Background: The edema of left colonic and pelvic mesenteric adipose tissues has long been recognized in surgery as a characteristic feature of radiation proctitis (RP). However, the correlation between mesenteric adipose volume and RP has not been extensively clarified. The purpose of this study was thus to assess the variation of left colonic and pelvic mesenteric adipose volume in RP. Methods: From March 2013 to June 2015, the data of 52 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy, including 23 patients with RP and 29 with non-RP (nRP), were retrieved. The mesenteric adipose volume was quantified via a computed tomography (CT) reconstruction method. Corresponding analyses were conducted to observe the correlation between the relative change of mesenteric adipose volume and the thickening degree of the rectal wall. Results: The baseline data of the RP group and the nRP group were comparable. There was no significant difference in the relative change of the left colonic mesenteric adipose volume in each vertebral space from the third lumbar vertebra to the first sacral vertebra before and after radiotherapy. The relative change of pelvic mesenteric adipose volume (ΔVp%) was notably higher in the RP group compared to the nRP group. With a ΔVp% cutoff value of 3.67%, the sensitivity and specificity for the diagnosis of RP were 65.2% and 86.2%, respectively. According to the correlation analysis, ΔVp% in the RP group was significantly correlated with the thickening degree of the rectal wall after radiotherapy (r=0.47, P=0.024). Conclusions: The increment of the relative change of pelvic mesenteric adipose volume quantitatively measured by CT can be clinically useful in identifying RP.
Precise extrinsic afferent (visceral sensory) and efferent (sympathetic and parasympathetic) innervation of the gut is fundamental for gut-brain crosstalk. Owing to the limitation of intrinsic markers to distinctively visualize the three classes of extrinsic axons, which intimately associate within the gut mesentery, detailed information on the development of extrinsic gut-innervating axons remains relatively sparse. Here, we mapped extrinsic innervation of the gut and explored the relationships among various types of extrinsic axons during embryonic development in mice. Visualization with characterized intrinsic markers revealed that visceral sensory, sympathetic, and parasympathetic axons arise from different anatomical locations, project in close association via the gut mesentery, and form distinctive innervation patterns within the gut from embryonic day 10.5 to 16.5. Genetic ablation of visceral sensory trajectories results in the erratic extension of both sympathetic and parasympathetic axons, implicating that afferent axons provide an axonal scaffold to route efferent axons. Co-culture assay further confirmed the attractive effect of sensory axons on sympathetic axons. Taken together, our study provides key information regarding the development of extrinsic gut-innervating axons occurring through heterotypic axonal interactions and provides an anatomical basis to uncover neural circuit assembly in the gut-brain axis.Significance StatementUnderstanding the development of extrinsic innervation of the gut is essential to unravel the bidirectional neural communication between the brain and the gut. Here, with characterized intrinsic markers targeting vagal sensory, spinal sensory, sympathetic, and parasympathetic axons, respectively, we comprehensively traced the spatiotemporal development of extrinsic axons to the gut during embryonic development in mice. Moreover, in line with the somatic nervous system, pre-target sorting via heterotypic axonal interactions is revealed to play critical roles in patterning extrinsic efferent trajectories to the gut. These findings provide basic anatomical information to explore the mechanisms underlying the process of assembling neural circuitry in the gut-brain axis.
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Digestive symptoms are prominent in a significant fraction of Coronavirus disease-2019 (COVID-19) patients. Detection of the active virus (SARS-CoV-2) and viral RNA have been noted in the stool samples of some COVID-19 patients which indicates potential infectivity and replication of the virus in the human gut. Gut infectivity by the virus has been further substantiated by recent in situ and in vivo studies. Also, there are preliminary indications for the involvement of mesentery in COVID-19. In this article, we deliberate upon emerging empirical evidence indicating possible involvement of gut and mesentery in COVID-19 pathogenesis. Cite as: Kumar, Ashutosh and Kumari, Chiman and Faiq, Muneeb A. and Pareek, Vikas and Narayan, Ravi K., SARS-CoV-2 infectivity vis-a-vis human gut and mesentery: Pathogenic implications for COVID-19 (June 27, 2020). Available at SSRN:
Literature Review
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Ileal pouch-related adenocarcinoma remains a rarity; thus, guidelines on treatment are currently lacking. We present this case of a 54-year-old man who underwent restorative proctocolectomy with stapled ileal pouch–anal anastomosis formation for familial adenomatous polyposis during the 1980s. Despite undergoing annual surveillance endoscopy, the patient was noted to be anaemic and passing fresh blood per anus. Endoscopy and radiological investigation revealed the presence of a pouch-related adenocarcinoma. This was subsequently treated with short-course radiotherapy and pouch excision. The patient remains well until now and will follow six-monthly surveillance protocols with a transition to annual surveillance after 2 years.
Purpose of review: This article assesses the role of the mesentery in Crohn's disease. Recent findings: The mesentery is centrally positioned both anatomically and physiologically. Overlapping mesenteric and submucosal mesenchymal contributions are important in the pathobiology of Crohn's disease. Mesenteric contributions explain the topographic distribution of Crohn's disease in general and mucosal disease in particular. Operative strategies that are mesenteric based (i.e. mesocolic excision) may reduce rates of postoperative recurrence. Summary: The net effect of mesenteric events in Crohn's disease is pathologic. This can be targeted by operative means. VIDEO ABSTRACT:
A recent paper indicates that intraoperative and postoperative complications associated with complete mesocolic excision are increased when compared with conventional surgery. Variability in complication rates between studies highlights the need for standardization in colorectal surgery. This process should start by addressing factors that have hampered standardization to date.