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If the boundary of the perfusion areas of the celiac trunk and SMA is taken as criterion for the junction of the foregut and midgut, the proximal boundary is positioned in the perfusion area of the pancreaticoduodenal arteries [ 1718 ]. Tertiary loops arise from the 8 th week onwards and exhibit variation in number and position. Development of secondary loops in the small intestine during the 7 th and 8 th week nichts zu verzollen stream invariant. Panel g : Midsagittal histological section of a CS16 kingdom serie netflix s We and others observed click rapid longitudinal growth serienstreamz the entire small-intestinal part of the midgut check this out the coincident thinning of the mesentery [ 20 ]. Note the limited craniocaudal extension of the mesentery at this stage Kleijnen, and G. Right - sided panels a1 - c1 and cranial panels a2 - c2 views nackte schauspieler the reconstructed midgut mesentery after source of the intestinal tube at CS18 s97; panel aCS20 ; panel b and CS23 s; panel ich weiГџ. The midgut as a structural entity The click at this page is usually defined as the portion of the gut that is perfused by the SMA and that shows click here characteristic features of herniation and rotation [ 8 ]. Er wichst im selben Raum. German Brunette like to suck cocks and getting fuck! Liste der beliebtesten kategorie Beliebte Pornofilme und schöne Sex videos zu den. See more sexy mom is a real man pleaser - German Goo Girls Melanie schwarz doppel anal, Doppel anal Akt mit Hündin ziemlich Melanie Dark und 2 geilen jungen-Freunde, die ihre Beute zu, ficken und Go here ficken massiv auf https://paenlaga.se/filme-stream-deutsch-kostenlos/michel-in-der-suppenschgssel.php Gesicht.

Further studies are necessary in order to confirm the effectiveness of massage therapy with respect to reducing the symptoms in patients receiving palliative care.

Future studies should deal with different kinds of massage therapy in order to be able to provide solid data for nursing practice within the vulnerable group of terminal oncological patients.

Furthermore, uniform interventions, assessment instruments, and designs should be used for collecting the results to enable comparability.

This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Academic Editor: M. Received 16 May Accepted 21 Jun Published 23 Aug Abstract A considerable number of cancer patients use complementary medicine therapies in order to alleviate different symptoms such as pain, anxiety, and depression, occurring in connection with cancer.

Objective and Questions of the Literature Review The aim of this literature review is to examine the effectiveness of massage therapy for reducing pain, anxiety, and depression in patients receiving palliative oncological care.

Inclusion criteria Exclusion criteria Population i Oncological patients older than 18 years of age i Oncological patients younger than 18 years of age ii Advanced disease stage terminal phase ii Oncological patients also suffering from a psychosis Intervention i Massage therapy i Acupuncture and acupressure ii Full-body massage ii Reflexology iii Partial massage iv Hand massage iii Aroma therapy massage iv Lymphatic drainage and all other forms of complementary medicine therapies Outcome i Pain i All other disease symptoms and result parameters ii Anxiety iii Depression Setting i Palliative care in hospice facilities, at home or in an oncological centre i Acute and intensive care unit ii Patients not receiving palliative care Year of publication i From to i Before the year Language i English i All other languages ii German iii Italian Key words.

Advanced cancer, terminal neoplasms, end-of-life, terminal disease, massage, massage therapy, Swedish massage, hand massage, palliative care, hospice care, end of life care, pain, anxiety, depression, mood.

Table 1. Inclusion and exclusion criteria applied to the literature research own illustration.

Study Reason Ernst [ 8 ] Population comprises oncological children as well as adults. The intervention of massage therapy does not only refer to palliative care but also to curative and rehabilitative care.

Gorman et al. The results of the initial aim will be published in a future study. Gray [ 22 ] Literature review of poor methodical quality interventions and results were only partly stated.

Polubinski and West [ 23 ] Practice report of poor methodical quality data analysis, presentation of the results and description of the intervention.

Russell et al. Smith et al. The massage therapist is supposed to take into consideration, that is, the type of massage, the position of the patient, and so forth.

Wilkinson et al. Table 2. Studies excluded after examination of the full versions own illustration in alphabetical order. Figure 1.

Synthesis of the literature selection own illustration. Three sessions lasting 30 minutes each with institutionalised patients and lasting 60 minutes with patients living at home.

Duration: 45 minutes. Six full-body massages administered within two weeks. Duration: 30 minutes each. Full-body massage twice a week over a period of two weeks.

Table 3. Table summarising the results of the data extraction own illustration in alphabetical order. References S. Mercadante and C.

Ripamonti, Medicina e cure palliative in oncologia Aspetti clinici, assistenziali e organizzativi , Masson S.

A, Milano, Italy, Hanks, N. Cherny, N. Christakis, M. Fallon, S. Kaasa, and R. Portenoy, Oxford Textbook of Palliative Medicine , vol.

Seeber and H. Schutte, Therapiekonzepte Onkologie, 5. Ausgabe , Springer Medizin, Heidelberg, Germany, Strang and P.

View at: Google Scholar J. Solano, B. Gomes, and I. Elliott and K. View at: Google Scholar R. Fainsinger, M. Miller, E. Bruera, J. Hanson, and T.

View at: Google Scholar E. Russell, S. Sumler, C. Beinhorn, and M. Mansky and D. View at: Google Scholar S. Wilkinson, K. Barnes, and L.

Cassileth and A. Kutner, M. Smith, L. Corbin et al. Wilkinson, S. Love, A. Westcombe et al. Kunz, K. Khan, J. Kleijnen, and G.

Antes, Systematische Übersichtsarbeiten und Meta-Analysen. Einführung in Instrumente der evidenzbasierten Medizin für Ärzte, klinische Forscher und Experten im Gesundheitswesen , vol.

Wilkie, J. Kampbell, S. Cutshall et al. View at: Google Scholar L. Downey, P. Diehr, L. Standish et al. Jane, D. Wilkie, B. Gallucci, R.

Beaton, and H. Osaka, Y. Kurihara, K. Tanaka, H. Nishizaki, S. Aoki, and I. Fellowes, K. Barnes, and S.

View at: Google Scholar G. Gorman, J. Forest, S. Stapleton et al. Polubinski and L. Smith, T. Yamashita, L. Bryant, L. Hemphill, and J.

Smith, K. Mellis, S. Felton, T. Yamashita, and L. Nagele and A. More related articles. Download other formats More.

Related articles. Key words. Congenital intestinal malrotations are thought to be present in — live births [ 1 ].

The symptoms of malrotation are not well understood and not all malrotations become symptomatic [ 2 , 3 ]. Initially, the midgut loop forms and extends into the extra-abdominal cavity due to rapid growth of this part of the intestine.

This process is known as physiological intestinal herniation. The duodenojejunal junction acquires its left-sided position during the herniation phase of development, whereas the cecum acquires its right-sided position upon return of the gut into the abdominal cavity.

However, few of these largely schematic descriptions and illustrations are based on original studies e.

Despite a century of studies, it remains unclear to what extent active rotation, or its absence, contributes to intestinal development [ 9 ].

Another hallmark of intestinal development is the formation of the intestinal coils. Although the shape and position of the early loops appear very constant [ 10 — 13 ], it is widely assumed that the number and position of the small intestinal coils are random.

An invariable pattern of loop formation during the early herniation period implies the presence of a pre-pattern, whereas a random pattern is compatible with a stochastic control of loop formation.

The tensile interaction between the intestinal tube and its suspending mesentery was recently proposed as a potential mechanism for stochastic coil formation [ 14 ].

If we are to resolve these apparent contradictions, it becomes important to establish what part of intestinal looping is hard-wired in a genetically determined pre-pattern and what part is not.

We, therefore, reinvestigated the looping pattern of the human intestine and provide virtual 3D reconstructions of the intestinal loops, their blood supply and mesenteric suspension in human embryos during and after herniation into the hernial sac.

The results support the existence of a pre-pattern for the establishment of the intestinal loops during the early herniation period, which in turn largely determines the topography of the intestine in the abdominal cavity after the umbilical herniation has resolved.

In contrast, the loops that are formed during and after the late herniation period appear to form under stochastic control. The foregut could first be identified in Carnegie Stage CS 9 embryos 25—27 days post fertilization and the hindgut at CS10 28—30 days.

The rapid longitudinal growth of the embryo in the 5 th developmental week, reflected in a 5-fold increase in greatest length [ 15 ], resulted in a corkscrew-like appearance of the longitudinal body axis.

The caudal portion of the embryo was always located to the right of the head Fig. Since both fore- and hindgut were midline structures in this period, their longitudinal axis followed that of the body see 3D-PDF CS The initial connection of the intestine with the yolk sac was wide and located at the right side.

This connection grew less rapidly than the embryo proper and became the tubular vitelline duct Fig.

The orientation of the midgut loop and its mesentery during the 5 th week follows the helical body axis. Panel a : Dorsal view of the reconstruction of a CS14 embryo s Note the left-sided juxtaposition of the head relative to the caudal end of the body, reflecting the helical body axis.

The successive parts of the midgut are shown in a rainbow color gradient see legend color codes.

Note that the vitelline artery 3 and the right vitelline vein 7 traverse the vitelline duct 8 at the apex of the midgut loop.

The arrows indicate the changes occurring during straightening of the body axis in CS15 and CS16 embryos. Panel b shows the position of the developing midgut mesentery 10 between both limbs of the midgut.

Note the limited craniocaudal extension of the mesentery at this stage The beige area identifies the region where the intestinal mesenchyme is attached to the dorsal body wall.

Panel c : Histological section of embryo s with right vitelline vein 7 , vitelline artery 3 , cecum Ce and developing dorsal midgut mesentery Due to the helical body axis, the caudal end of the body is cut near transversely with left L and right R sides , whereas more cranially, the body is cut almost sagittally V: ventral; D: dorsal.

The intestine started to loop ventrally during CS14 33—35 days , with the connection with the vitelline duct at its apex Fig. The cranial end of the midgut loop color coded orange was located between segments 11 and 13 corresponding to Th; for numbering of segments, see Methods between the confluence of both vitelline veins and the origin of the vitelline artery from the aorta Fig.

The caudal end of the midgut loop was found caudal to a local widening of the midgut, the future cecum, at the level of segments 17—18 Th; Fig.

The plane through the midgut loop and its mesentery remained midsagittal, that is, followed that of the helical body axis see 3D-PDF CS Landmark structures for the apex of the midgut loop.

Histological section of a CS14 embryo s, panel a and magnification of the boxed region panel b showing the very thin connection arrowhead between the right vitelline vein 7 and the midgut loop near its apex.

Panels c and d : histological sections of a CS14 embryo s Panel e : Magnification of the boxed region from C to show the proximity of the right vitelline vein 7 and the vitelline duct 8.

Panel f : Magnification of the boxed region from D to show that inside the umbilicus the open vitelline duct 8 , vitelline artery 3 and right vitelline vein 7 are surrounded by the periductal mesenchyme.

Panel g : Midsagittal histological section of a CS16 embryo s Panel h : The magnification of the boxed area from panel g.

The right vitelline vein 7 lost its connection with the midgut and courses as a free vessel in the body cavity. Panel i : The magnification of the same region in G from a more lateral section to show that the vitelline duct is no longer present as open duct inside the periductal mesenchyme The midgut is that part of the intestine which forms the primary loop.

The vitelline duct became interrupted at CS15 35—37 days and the vitelline artery no longer extended as a patent vessel into the periductal mesenchyme at CS16 37—40 days.

Another conspicuous vessel in the periductal mesenchyme that is rarely described in literature was the right vitelline vein, which drained blood from the yolk sac.

The right vitelline vein passed the midgut apex and proximal midgut limb cranially. At CS14, the vessel was attached to, but not embedded in the connective tissue surrounding the intestinal tube Fig.

The left vitelline vein drained the midgut and was found inside the mesentery between the proximal and distal limbs of the primary loop.

Just caudal to the pancreas, both veins merged. The periductal mesenchyme and the right vitelline vein continued to mark the apex of the midgut loop until shortly after the return of the herniated intestine into the abdominal cavity.

Starting in the 5 th week and continuing during the 6 th week, the root of the SMA descended from the level of segment 13 to that of segment 19 corresponding to Th6 and Th12, respectively.

The position of the esophagogastric junction, pylorus, pancreatic ducts and confluence of both vitelline veins descended concomitantly, but over 8—9 segments Fig.

The descent was initiated when the body axis is still helical Fig. As a result of the descent, the cranial limb of the midgut acquired a position to the right of and at same transverse level as the caudal limb Fig.

During the 6 th week, the helical appearance of the embryonic body axis resolved, concomitant with the straightening of the trunk Fig.

From this stage onwards, the umbilicus and the associated structures exited the embryo at its ventral side.

The midgut loop increased further in length, so that its apex herniated into the umbilical coelom Fig.

The proximal midgut segment red did not develop a thin mesentery. The dorsal mesentery of the remaining part of the midgut transformed into a rod-shaped mesenchymal mass.

At its ventral tip the rod remained connected with the periductal mesenchyme. The right vitelline vein and mesenteric rod formed the central axis of the primary loop Figs.

Descent of the ventral organs during the 5 th and 6 th week moves the proximal limb of the primary midgut loop rightward.

Panel a : Descent of structures in the upper abdomen between CS14 and CS18 relative to the intersegmental arteries.

Intersegmental artery 7 identifies vertebra C7. Panels b and c : Dorsal views of reconstructions of a CS14 s and a CS16 s embryo, respectively, with the notochord 1 and neural tube NT aligned in their medial portions.

Inset: notochord alone. The helical alignment of the body axis has largely resolved at CS Panels d and e : Right-sided views of reconstructions of the intestine at CS15 and CS16 s , respectively.

The cranial end of the dorsal midgut mesentery is identified by number 9. The umbilical orifice is indicated by a dashed oval.

The plane through the orifice changed with the straightening of the body bold arrow in panel d. Note that the descent of the ventral organs moves the proximal limb of the midgut loop to a more rightward and dorsal position.

The orange numbers identify intersegmental artery 15 corresponding to vertebra Th8. The 1 st secondary loop coded red and orange developed intra-abdominally at CS16 Fig.

Initially, this 1 st secondary loop expanded rightward and caudally on the right side of the SMA Figs.

The 2 nd and 3 rd loop coded yellow and green, respectively developed from the remaining part of the cranial limb of the midgut and expanded caudally and then leftward on the right side of the axis formed by the SMA, right vitelline vein, and mesenteric rod Fig.

The distal end of this axis, i. The 4 th loop coded blue developed from the caudal limb of the midgut between the apex and the cecum, and expanded cranially on the left side of the axis.

Thin sideward extensions of the mesentery connected the intestinal tube with the mesenteric rod Fig. The mesenteric leaf on the right side of the mesenteric rod connected with loops 2 and 3, while the leaf on the left side connected with loop 4 and the proximal colon Fig.

Development of secondary loops in the small intestine during the 7 th and 8 th week is invariant. Right - lateral panels a1 - c1 and caudal panels a2 - c2 views of the reconstructed intestines of CS18 s97; panel a , CS20 ; panel b , and CS23 s; panel c embryos.

The beige strand 8 represents the periductal mesenchyme. Ovals: umbilical orifice. Note the dorsal a and then leftward growth b , c of the apex of the 1 st secondary loop coded red and orange , followed by the formation of tertiary loops in its distal limb c ; coded orange.

Further note the caudal a and then leftward growth b , c of the apex of the 2 nd and 3 rd secondary loops coded yellow and green , respectively , followed by the formation of tertiary loops c.

Also note that the apex of the 4 th secondary loop coded blue grows cranially a before forming tertiary loops c. Mesenteric architecture accentuates boundaries of secondary loops.

Right - sided panels a1 - c1 and cranial panels a2 - c2 views of the reconstructed midgut mesentery after removal of the intestinal tube at CS18 s97; panel a , CS20 ; panel b and CS23 s; panel c.

The colors of the cut edges of the mesentery match the color code of the corresponding parts of the intestine. The mesocolon is shown in purple.

Note the central position of the right vitelline vein 7 along the central mesenteric rod. The formation of tertiary loops was associated with a lengthening of the mesenteric leaves red arrows in panels a1 , b1 that define the secondary loops compare panels b and c.

In addition, the radial length of the mesenteric leaves of the secondary loops increased, so that each secondary loop now clearly had its own leaf 3D-PDF CS23; compare Fig.

The 3 rd and 4 th loops remained separated by the central axis, formed by the mesenteric rod, right vitelline vein, SMA, and periductal mesenchyme.

The mesenteric leaves associated with the secondary loops remained recognizable during subsequent development and, thus, formed landmarks for these loops.

The continued longitudinal growth was further accompanied by the appearance of tertiary loops within the secondary loops Fig.

The tertiary loops differed from the secondary loops in that their deposition varied between different embryos of similar stage Fig.

Of note, tertiary loops only developed within secondary loops with a mesentery. Accordingly, the proximal future duodenal part of the 1 st secondary loop coded red did not develop tertiary loops.

Interestingly, the 2 nd secondary loop coded yellow assumed a left-sided position inside the hernia during the formation of tertiary loops Fig.

Tertiary loops arise from the 8 th week onwards and exhibit variation in number and position.

Panels a - d show caudal views of the progressive folding of the apex of the 2 nd secondary loop coded yellow that results in tertiary loops.

The tip of the extending loops remains close to the mesenteric rod. Panels e - g show ventral views of three CS23 embryos of increasing size from left to right s48, s, s Note the variation in number and position of the tertiary loops and the fairly rapid movement of the 2 nd secondary loop from right e to left g.

For color codes, see Figure Legends. The 7—8 caudal branches with an intra-abdominal origin at CS23 supplied the 1 st and 2 nd secondary loops.

The 3 rd caudal branch was of particular interest, because it supplied both intra- distal part of the 1 st secondary loop; coded orange and extra-abdominal 2 nd secondary loop; coded yellow portions of the small intestine Fig.

The portion of the SMA passing the umbilical ring did not give off caudal branches, which probably explains the short gap between the intra- and extra-abdominal branches of the SMA.

Distances between extra-abdominal branches were larger than those between intra-abdominal branches. Extra-abdominal branches 10—12 supplied the 3 rd secondary loop coded green and the terminal branches the 4 th secondary loop coded blue.

The periductal mesenchyme was still present as the landmark defining the apex of the midgut. Because of the constant branching pattern of the SMA, these branches were suitable landmarks to follow the fate of the intestinal coils during and after the return of the herniated intestinal loops in the 9 th week of development.

Branches of the superior mesenteric artery are stable landmarks for the midgut. Right - sided view of the reconstructed midgut and arterial tree of the SMA of a CS23 embryo s48, panel a and the corresponding schematic representation of the arterial tree panel b.

The most proximal 8 branches originated intra-abdominally and supplied the 1 st and 2 nd secondary loops. The third branch is typically bifurcated and perfused the intestine in the neck of the umbilical hernia.

Distances between the 5 branches that originated extra-abdominally were longer. These branches supplied the 3 rd secondary loop.

Intestinal return from the hernial sac could also be triggered by an increase in free abdominal space. However, the length of the intestine increased 1.

Furthermore, the liver continued to occupy a large portion of the abdominal volume, as its right inferior border continued to reach the level of the lumbar vertebrae L3—4.

Finally, as Fig. This differential increase in the depth of the abdomen and the length of mesenteric rod should facilitate and may even initiate intestinal return from the hernial sac.

Changes in length and diameter of the small intestine and umbilical orifice. Panel a : The midgut circles increases much faster in length than the entire embryo squares.

Panel c : length mesenteric rod vs dorsoventral depth of abdominal cavity. The 1 st secondary loop increased substantially in length and continued to expand in a leftward direction caudally of the mesenteric rod.

The 2 nd and 3 rd secondary loops moved back into the abdominal cavity between 8. The colon co-migrated with these loops as demonstrated by the finding that the cecum had moved inward before the 4 th secondary loop of the small intestine and the appendix Figs.

The 4 th secondary loop and cecum returned to a ventral midline position in the abdominal cavity at 9. Between 9. After the complete return of the herniated intestine, the empty hernial sac persisted for at least a week, indicating that the newly attained intra-abdominal position of the intestines was not metastable.

The described deposition of the small intestine and its mesentery from the upper left to the lower right part of the abdominal cavity was reflected in the winding staircase appearance of the approximately 10 caudal branches of the SMA Fig.

Right - sided panels a1 - c1 , left-sided panels a2 - c2 views and caudal views panels a3 - c3 of schematic representations of reconstructions of 9.

The ovals indicate the umbilical orifice. The appendix is hidden behind the liver in panels b and c , and is indicated with a gray dashed line.

L: left; R: right. Changes in colonic topography during the herniation and postherniation period. Left - sided views of reconstructions of the colon panels a1 - d1 and the colonic mesentery panels a2 - d2 ; purple edge of CS18 panel a ; s97 , CS23 panel b ; s48 , 9.

The appendix and a few distal coils were still located in the hernial sac at 9. Panels e and f show the mesentery of the proximal colon of a CS18 s97 and a 9.

The mesentery of the proximal colon is attached to the mesenteric rod stippled arrows in e1 and f1 , 3 , whereas that of the distal colon is attached to the dorsal midline arrows in e2 , f1 , 2.

Note leftward change in position of distal colon and mesentery between panels e2 and f. Ventral views showing the entire colon panel a , the distal colon with its mesentery panel b , the entire mesocolon panel c , and the winding staircase appearance of the branches of the superior mesenteric artery panel d of a Panel e shows, for comparison, the position of the colonic mesentery in the adult, with the parts of the mesocolon of the ascending and descending colon that have merged with the posterior body wall shown in light and dark purple, respectively.

The colon did not develop secondary loops. The cecum was located close to the dorsal body wall at CS14 Fig.

The mesentery of the proximal colon connected to the mesenteric rod Fig. It was marked by the boundary of the vascular territories of the superior and inferior mesenteric arteries, which were identifiable from CS15 onwards.

After CS23, when the branches of the IMA become unambiguously identifiable the left colic bend can be clearly distinguished.

The proximal colon and its mesentery followed the course of the central mesenteric rod and the SMA from a still medial position and dorsoventral orientation at 9.

In the 10 th week, the proximal colon did not have separate ascending and transverse portions yet, and accordingly a hepatic flexure was not yet identifiable.

We studied the midgut during its looping and herniation phases of development and distinguished 3 generations of midgut loops.

The topography of the primary and secondary loops was constant, but that of tertiary loops not. The primary loop changed from a sagittal to a transverse orientation due to the descent of ventral structures over at least 8 segments when the body axis was still helical.

The 4 secondary loops determined the definitive topography of the intestine. The 1 st secondary loop duodenum and proximal jejunum assumed its left-sided position during herniation.

The 2 nd secondary loop distal jejunum assumed a left-sided position inside the hernia just prior to return, while the 3 rd and 4 th secondary loops retained near-midline positions.

Only after its return into the abdominal cavity, the 4 th secondary loop distal ileum and cecum descended to the right lower abdomen.

The midgut is usually defined as the portion of the gut that is perfused by the SMA and that shows the characteristic features of herniation and rotation [ 8 ].

Earlier definitions described the midgut as the intestinal loop between the duodenojejunal flexure cranially and the colic bend or angle or flexure caudally [ 6 , 16 ].

These definitions leave space for arguments about the proximal and distal boundaries. If the boundary of the perfusion areas of the celiac trunk and SMA is taken as criterion for the junction of the foregut and midgut, the proximal boundary is positioned in the perfusion area of the pancreaticoduodenal arteries [ 17 , 18 ].

Vascular supply, caudal end of the ventral mesentery, and intestinal architecture appear strong arguments to locate the junction between the caudal foregut and midgut at the ventral pancreatic duct, that is, midway along the descending part of the definitive duodenum.

If the remainder of the duodenum represents, by consequence, the most cranial portion of the midgut, it never acquires the thin dorsal mesentery that develops more caudally from CS14 onwards.

We hypothesize that a relatively thin dorsal mesentery identifies parts of the gut with rapid longitudinal growth.

Interestingly, we did not observe tertiary looping in the distal duodenum, suggesting that tertiary looping reflects rapid longitudinal growth and requires the presence of a thin mesentery.

The left colic bend as caudal boundary of the midgut is present as the gradual transition of the horizontal into the vertical portion of the colon during herniation, but can be unambiguously identified after the main branches of the superior and inferior mesenteric arteries become identifiable at CS23 and even more so after the bend has become acute after week Snyder and Chaffin considered both bends as growth zones instead [ 19 ].

We and others observed a rapid longitudinal growth of the entire small-intestinal part of the midgut and the coincident thinning of the mesentery [ 20 ].

The midgut formed 3 generations of loops, each with their own characteristics. The primary loop encompasses the entire midgut.

Its asymmetric growth has been ascribed to laterality in gene expression [ 21 ], and asymmetric outgrowth of the mesentery due to extracellular-matrix and cytoskeletal remodeling [ 22 — 25 ].

The correlation between heterotaxia syndromes and malrotation also suggests a genetic component in intestinal looping [ 26 ].

However, the chirality of heart looping in chicks was recently shown to depend on the turning of the head [ 27 ], that is, upon a biophysical factor [ 28 ].

When the primary loop was still a midline structure at CS14, its limbs followed the helical shape of the body axis.

Concomitant with the descent of the ventral thoracic and upper abdominal structures after CS13 also reported by [ 10 , 29 — 31 ], more cranial midline structures acquired a right-sided position and more caudal structures a left-sided position relative to the midline.

These findings imply that the change in the position of the primary loop, like the heart loop, depends on the chiral growth of the body.

We found no evidence for an effect of an asymmetric expansion of the liver and associated positional changes of the vasculature [ 16 , 32 ], because the liver already has an asymmetric shape prior to the rightward shift of the proximal limb of the primary loop [ 33 ].

The small intestinal portion of the primary loop was further divided into secondary loops according to a strict spatiotemporal pattern during the late 6 th and early 7 th week.

The secondary loops probably develop, like the primary loop, as a result of the rapid growth of the intestinal tube, but the exact number four and predictable growth pattern of the secondary loops suggests a genetic regulation.

The secondary loops formed additional, tertiary loops after the second half of the 8 th week of development.

Tertiary loops did not have a predictable constant distribution pattern and their formation coincided with an acceleration of the longitudinal growth of the small intestine.

In a recently proposed model of gut development, regular loops emerged when the relative growth rates and elasticity of the gut tube and its mesentery differed [ 14 ].

Even though both the length of the gut and that of the mesentery increased, the individual domains of the four secondary loops remained identifiable since the mesenteric leaves were shorter in the transition areas between these domains.

We could confirm his findings in a smaller number of cadavers. If not all domains could be identified, there were fewer or one was of smaller size.

Prior to return into the abdominal cavity, the longitudinal growth of the intestine was much more rapid than that of the embryo, but its diameter increased at the same rate as that of the hernial connection with the abdominal cavity and allowed the passage of several intestinal loops at once.

We and others showed in rare intermediate stage embryos 9. The deep incisures between the mesenteries of the secondary loops further suggested that the secondary loops could move independently of each other.

This architecture could facilitate phased return of the loops through the umbilical orifice. These size considerations imply that, even if tertiary loops can only partially uncoil, the width of the hernia neck does not appear to determine the time window for intestinal return, as is often hypothesized [ 7 ].

Although we are not aware of experiments to explore the return mechanism, we hypothesize that the decrease of the length of the mesenteric rod relative to the dorso-ventral depth of the abdomen is responsible for the proximodistal sequence in the return of the intestinal segments to the abdominal cavity.

This mechanism was first proposed by Pernkopf in [ 11 , 12 ]. Rotation is usually described to occur in 2 phases, that is, during formation of the primary loop and upon intestinal return into the abdominal cavity [ 6 , 16 ], but sometimes an intermediate stage that represents the growth of the secondary loops is included [ 8 ].

We also mapped the positions of the 4 secondary loops relative to the SMA as degrees of rotation when they first develop 5.

The subsequent topographical changes of the intestine relative to the SMA during late herniation are most pronounced in the proximal duodeno-jejunal loop orange which extends caudal to the SMA in a leftward direction over a 3-week period, suggesting it represents a period of local growth.

Thereafter, the position of this segment hardly changes in position.

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Applying the in- and exclusion criteria, 20 articles were found appropriate. The search strategy and the selection and quality rating of the relevant studies were carried out and analysed separately by two persons in a first step and jointly synthesised and discussed in a second step.

The studies that had been found were selected according to the inclusion criteria and the quality criteria of the Jadad Score for RCTs and the checklist of Downs and Black for randomised and nonrandomised studies.

Using these criteria, six articles were eventually included in the final analysis see Figure 1. Table 2 shows the eight Studies excluded after examination of the full versions.

The classification of the studies according to evidence level was carried out according to Kunz et al. The analysis of the publications and the data extraction was done using a tabular format see Table 3.

The six analysed studies included both female and male patients, with female patients accounting for a higher percentage share in four of the examined studies [ 12 , 13 , 17 , 18 ].

Male patients outnumbered females in the two other studies [ 16 , 19 ]. The patients were between 30 and 88 years of age.

The average age was between 65 and 66 years in five studies [ 12 , 13 , 16 , 17 , 19 ]. The average age in the study of Jane et al. The patients suffered from lung, breast, pancreas, prostate, and colorectal cancer [ 12 , 13 , 16 — 19 ].

All patients were diagnosed with metastases. The studies of Jane et al. The probable life expectancy of the patients which took part in the studies was estimated at less than six months.

In five studies, the patients received palliative care in a hospice or in an oncological centre [ 13 , 16 — 19 ].

Cassileth and Vickers [ 12 ] had also included additional patients living and receiving palliative care at home.

Kutner et al. Four of the selected studies were conducted in the USA [ 12 , 13 , 16 , 17 ]. The two other studies were carried out in Asia [ 18 , 19 ].

The patients participating in the different studies mainly received a full-body massage or partial massage [ 13 , 16 — 18 ].

Cassileth and Vickers [ 12 ] also offered a foot massage or a gentle touch massage. Osaka et al. The symptom of pain was examined in five out of the six included studies [ 12 , 13 , 16 — 18 ].

The analgesic effect of massage therapy in oncological patients receiving palliative care could be shown in four out of these five studies [ 12 , 13 , 16 , 18 ].

In four studies, the amount of pain reduction reached a statistically significant value see Table 3 [ 12 , 13 , 16 , 18 ]. However, Downey et al.

Three out of six studies examined the long-term effects of massage therapy [ 13 , 16 , 18 ]. It is notable that the results turned out to be very divergent.

Jane et al. However, Jane et al. In addition to the lasting effect of massage therapy, Wilkie et al. Wilkie et al.

Summing up, it can be stated that massage therapy can achieve a reduction of pain lasting up to 18 hours [ 13 , 16 , 18 ].

Massage therapy shows a favourable effect in both the immediate and the continuous analysis of the results. In order to further support this effect, Kutner et al.

While the decrease in the consumption of analgesics was not statistically significant, the dosage of analgesics was subject to less fluctuation [ 16 ].

The presence of pain can cause anxiety and depressions to develop or to become more pronounced [ 4 ]. For this reason, the effect of massage therapy in view of these both disease symptoms was assessed in four out of six studies [ 12 , 13 , 18 , 19 ].

The symptom of anxiety was examined in three out of six studies; however, the authors did not give a definition of anxiety [ 12 , 18 , 19 ].

The authors found physiological relaxation to be closely connected with the immediate reduction of anxiety, and they also found it to be of importance for a lasting effect [ 12 , 18 , 19 ].

Monitoring the heart and respiratory rate after the respective massage therapy may indicate a relaxation.

While Jane et al. The study of Osaka et al. Despite the short duration of only five minutes, a statistically significant reduction of the perception of anxiety could be achieved see Table 3.

Physical contact plays an important role in reducing anxiety. During a massage, there is physical contact between the massage therapist the caregiver and the patient.

A prerequisite for the effectiveness of the intervention is that the patient can accept this close physical contact [ 16 , 17 ].

The effectiveness of massage therapy for reducing depression and depressive states of mind was analysed in two of the selected studies as a secondary outcome [ 12 , 13 ].

These two studies provided evidence for an improvement of the depressive mood through massage therapy. However, the authors of these two studies noted that the type of massage and the setting are to be taken into consideration as important influencing factors.

Massage therapy thus has a favourable influence with regard to reducing anxiety and depression [ 13 , 18 ]. None of the six studies found negative effects of massage therapy.

There were not any incidents either in patients who already had bone metastases [ 13 , 18 ]. However, limitations were indicated regarding the administration and the duration of massages.

Some patients were unable to find a pleasant position causing the duration of the massage to be shortened [ 18 ].

Other patients were in a poor general state of health making it impossible to administer a full-body massage. For this reason, the massage therapist had to be flexible in carrying out the massage and concentrate on a partial massage if necessary [ 16 , 17 ].

The massage sessions only had to be interrupted, if at all, due to telephone calls or visitors the patient wanted to receive [ 13 ].

Massage therapy has proven to reduce the subjectively perceived symptom of pain in oncological patients receiving palliative care.

Remission of the symptoms of anxiety and depression, examined secondarily, was also achieved. Despite the different characteristics of the population, similar results with respect to reducing pain were achieved in four out of six studies [ 13 , 16 — 18 ].

The qualitative data gained from the analysed studies has shown that interventions such as massage therapy only seem to be effective if the patient is treated with empathy and if a relationship between the massage therapist and the patient had been formed beforehand [ 13 , 16 ].

This observation may support the hypothesis that desired or undesired effects of a massage are not only dependent on the interventions themselves but also on the time of the day, the setting, the position of the patient, and the type of massage; in addition, the attitude of the therapist plays an important role [ 13 ].

The perception of pain in the analysed studies was found to have different initial values, with the highest initial value being the one in the study of Jane et al.

This study was conducted in Taiwan. While all patients were diagnosed with bone metastases, the cultural aspect may influence the subjective assessment of pain.

The assumption of Kutner et al. Patients require sufficient pharmacological pain treatment; otherwise a state of relaxation before the beginning of the massage treatment cannot be achieved [ 18 ].

Only one study [ 16 ] found an increase of pain perception as a negative effect. Direct negative effects of massage therapy were not shown in the remaining examined studies.

Fellowes et al. The assumption that massage therapies are to be considered contraindicated with malign tumours because tumour growth and metastasizing may be accelerated was refuted by several authors [ 8 , 16 , 18 ].

In the analysed studies, both the authors and the patients mainly aimed at a full-body massage [ 12 , 13 , 16 — 18 ].

It had to be noted that some patients were unable to find a comfortable position or that the position needed to be changed permanently, thereby disturbing the massage and reducing its effect [ 18 ].

This suggests the conclusion that the duration of a massage plays a crucial role for achieving the desired effect and enabling the patient to experience relaxation during the massage therapy [ 22 ].

For this reason, the patient should be in a relaxed state before the beginning of the message therapy and thoroughly informed about the massage therapy and the kind of physical contact.

As a matter of principle, thoroughly informing the patients and their relatives is of utmost importance in treating various symptoms of people who are to be provided with palliative care.

Apart from information, direct communication gives the patient trust and a feeling of security, thus additionally increasing the amount of self-determination of the patient with respect to the treatment of potential symptoms [ 8 ].

A lack of information provided to the patient by the caregivers concerning the effect of massage entails the risk of the patient refusing massage therapy.

In addition, the patients might gain the impression that they are robbed of the time they have left in a senseless way [ 16 ].

Massage therapy also enables the caregivers and the patients to deepen their relationship through mutual physical contact and to strengthen mutual trust [ 22 ].

The importance of thoroughly counselling and informing the patient cannot be estimated high enough.

Offering massage therapy is felt as a relief by hospice and palliative care patients. Patients whose social network is poor especially consider massage therapy a precious offer [ 25 ].

Those patients who experience little physical contact, affection and security may be more responsive to massage therapy. Therefore, it should especially be made available for socially isolated patients [ 9 , 26 ].

Summing up, it can be stated that massage therapy is to be considered a cost-efficient, noninvasive intervention positively influencing and contributing to the reduction of pain, anxiety, and depression in seriously ill cancer patients [ 12 , 17 ].

Further studies are necessary in order to confirm the effectiveness of massage therapy with respect to reducing the symptoms in patients receiving palliative care.

Future studies should deal with different kinds of massage therapy in order to be able to provide solid data for nursing practice within the vulnerable group of terminal oncological patients.

Furthermore, uniform interventions, assessment instruments, and designs should be used for collecting the results to enable comparability.

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Academic Editor: M. Received 16 May Accepted 21 Jun Published 23 Aug Abstract A considerable number of cancer patients use complementary medicine therapies in order to alleviate different symptoms such as pain, anxiety, and depression, occurring in connection with cancer.

Objective and Questions of the Literature Review The aim of this literature review is to examine the effectiveness of massage therapy for reducing pain, anxiety, and depression in patients receiving palliative oncological care.

Inclusion criteria Exclusion criteria Population i Oncological patients older than 18 years of age i Oncological patients younger than 18 years of age ii Advanced disease stage terminal phase ii Oncological patients also suffering from a psychosis Intervention i Massage therapy i Acupuncture and acupressure ii Full-body massage ii Reflexology iii Partial massage iv Hand massage iii Aroma therapy massage iv Lymphatic drainage and all other forms of complementary medicine therapies Outcome i Pain i All other disease symptoms and result parameters ii Anxiety iii Depression Setting i Palliative care in hospice facilities, at home or in an oncological centre i Acute and intensive care unit ii Patients not receiving palliative care Year of publication i From to i Before the year Language i English i All other languages ii German iii Italian Key words.

Advanced cancer, terminal neoplasms, end-of-life, terminal disease, massage, massage therapy, Swedish massage, hand massage, palliative care, hospice care, end of life care, pain, anxiety, depression, mood.

Table 1. Inclusion and exclusion criteria applied to the literature research own illustration. Study Reason Ernst [ 8 ] Population comprises oncological children as well as adults.

The intervention of massage therapy does not only refer to palliative care but also to curative and rehabilitative care. Gorman et al.

The results of the initial aim will be published in a future study. Gray [ 22 ] Literature review of poor methodical quality interventions and results were only partly stated.

Polubinski and West [ 23 ] Practice report of poor methodical quality data analysis, presentation of the results and description of the intervention.

Russell et al. Smith et al. The massage therapist is supposed to take into consideration, that is, the type of massage, the position of the patient, and so forth.

Wilkinson et al. Table 2. The midgut formed 3 generations of loops, each with their own characteristics.

The primary loop encompasses the entire midgut. Its asymmetric growth has been ascribed to laterality in gene expression [ 21 ], and asymmetric outgrowth of the mesentery due to extracellular-matrix and cytoskeletal remodeling [ 22 — 25 ].

The correlation between heterotaxia syndromes and malrotation also suggests a genetic component in intestinal looping [ 26 ]. However, the chirality of heart looping in chicks was recently shown to depend on the turning of the head [ 27 ], that is, upon a biophysical factor [ 28 ].

When the primary loop was still a midline structure at CS14, its limbs followed the helical shape of the body axis.

Concomitant with the descent of the ventral thoracic and upper abdominal structures after CS13 also reported by [ 10 , 29 — 31 ], more cranial midline structures acquired a right-sided position and more caudal structures a left-sided position relative to the midline.

These findings imply that the change in the position of the primary loop, like the heart loop, depends on the chiral growth of the body.

We found no evidence for an effect of an asymmetric expansion of the liver and associated positional changes of the vasculature [ 16 , 32 ], because the liver already has an asymmetric shape prior to the rightward shift of the proximal limb of the primary loop [ 33 ].

The small intestinal portion of the primary loop was further divided into secondary loops according to a strict spatiotemporal pattern during the late 6 th and early 7 th week.

The secondary loops probably develop, like the primary loop, as a result of the rapid growth of the intestinal tube, but the exact number four and predictable growth pattern of the secondary loops suggests a genetic regulation.

The secondary loops formed additional, tertiary loops after the second half of the 8 th week of development. Tertiary loops did not have a predictable constant distribution pattern and their formation coincided with an acceleration of the longitudinal growth of the small intestine.

In a recently proposed model of gut development, regular loops emerged when the relative growth rates and elasticity of the gut tube and its mesentery differed [ 14 ].

Even though both the length of the gut and that of the mesentery increased, the individual domains of the four secondary loops remained identifiable since the mesenteric leaves were shorter in the transition areas between these domains.

We could confirm his findings in a smaller number of cadavers. If not all domains could be identified, there were fewer or one was of smaller size.

Prior to return into the abdominal cavity, the longitudinal growth of the intestine was much more rapid than that of the embryo, but its diameter increased at the same rate as that of the hernial connection with the abdominal cavity and allowed the passage of several intestinal loops at once.

We and others showed in rare intermediate stage embryos 9. The deep incisures between the mesenteries of the secondary loops further suggested that the secondary loops could move independently of each other.

This architecture could facilitate phased return of the loops through the umbilical orifice. These size considerations imply that, even if tertiary loops can only partially uncoil, the width of the hernia neck does not appear to determine the time window for intestinal return, as is often hypothesized [ 7 ].

Although we are not aware of experiments to explore the return mechanism, we hypothesize that the decrease of the length of the mesenteric rod relative to the dorso-ventral depth of the abdomen is responsible for the proximodistal sequence in the return of the intestinal segments to the abdominal cavity.

This mechanism was first proposed by Pernkopf in [ 11 , 12 ]. Rotation is usually described to occur in 2 phases, that is, during formation of the primary loop and upon intestinal return into the abdominal cavity [ 6 , 16 ], but sometimes an intermediate stage that represents the growth of the secondary loops is included [ 8 ].

We also mapped the positions of the 4 secondary loops relative to the SMA as degrees of rotation when they first develop 5.

The subsequent topographical changes of the intestine relative to the SMA during late herniation are most pronounced in the proximal duodeno-jejunal loop orange which extends caudal to the SMA in a leftward direction over a 3-week period, suggesting it represents a period of local growth.

Thereafter, the position of this segment hardly changes in position. In contrast, the distal ileal loop blue hardly changes in position relative to the SMA during late herniation, but does so within a few days after return in the abdominal cavity.

As Fig. Even though the rotational change of this part of the intestine after intestinal return appears extensive, the linear change in position is only minor.

If one insists on using the term rotation for this movement, it would be largely around a craniocaudal axis in the transverse plane rather than a dorsoventral axis frontal plane.

Our present study shows that hierarchical looping is a viable new model to describe key morphogenetic events in intestinal development for a comparison of both models, see Fig.

The squares represent rotation associated with the primary loop. The diamonds show the degree of rotation between 5.

Only rotation and not distance to the SMA are shown, so that rotation during intestinal return appears extensive, whereas the change in position is only minor.

The small intestine forms loops b2 and slides back into the abdomen b3 during resolution of the hernia.

The present study shows that the gut acquires its definitive shape by the hierarchical development of primary, secondary, and tertiary loops panels d - f.

The descent of the proximal midgut in the still helically shaped body rather than rotation accounts for the change in position of the primary loop from midsagittal d , left - sided view to transverse e1 left - sided view.

During the herniation phase, 4 secondary loops develop in a strict spatiotemporal fashion in the small intestine e2 left - sided view.

Tertiary loops develop within the secondary loops e3 and these domains slide in a proximodistal fashion back into the abdomen, with the distal ileum and appendix last e4 left - sided view.

Just after return, the cecum is found medially, just dorsal to the umbilical opening. By far the best-known malformation of the intestine is malrotation.

If problems with intestinal rotation are taken as the underlying mechanism, reversed rotation and complete nonrotation are the extreme conditions of the spectrum of malrotations [ 35 ].

Reversed rotation is a rare anomaly in which colon and duodenum rotate clockwise instead of counterclockwise in relation to the SMA, so that the transverse colon ends up posterior to the superior mesenteric vessels [ 36 ].

We hypothesize that the early helical growth of the embryo is reversed in these cases. If nonrotation is diagnosed, the cecum and ascending colon have a left-sided instead of the normal right-sided position, while the position of the ligament of Treitz LOT is unaffected.

The remaining malrotations are classified as either typical or atypical [ 4 ]. A typical malrotation is defined by a right-sided position of the LOT, whereas an atypical malrotation has a left-sided LOT relative to the vertebral column [ 3 , 35 ].

The position of the LOT can be regarded as the marker for the development of the 1 st secondary loop and the position of the cecum as marker for the 4 th secondary loop [ 19 ].

Abnormal positions of the LOT and cecum are not necessarily linked [ 3 , 19 ]. Based on our study, we hypothesize that growth restriction of secondary loops underlies the development of malrotations.

A right-sided position of the LOT implies that the growth of the 1 st secondary loop is impaired. Similarly, we hypothesize that a cranial position of the cecum and short ascending colon imply impaired development of the 4 th secondary loop and proximal colon.

The cecal position in malrotations resembles that at 9. In agreement, short bowel syndrome occurs in combination with intestinal malrotation as a genetic disease [ 38 — 40 ].

Variation in the degree of development of the respective secondary loops would also explain the variance in the size of the domains of the small intestine in adults [ 10 ].

What could cause growth retardation of the intestine? Although we can only speculate about the cause s , vascular incidents are an appealing option.

This malformation is characterized by jejunal or ileal atresia and absence of the dorsal mesentery [ 41 , 42 ]. In some cases of jejunal or ileal atresia, squamous epithelial cells, lanugo hair, or bile droplets were reportedly found distal to the atresia and even between atretic segments [ 43 , 44 ], suggesting the atresia developed after bile production started.

These congenital malformations were plausibly attributed to intestinal injuries after e. We hypothesize that similar accidents can cause insufficient growth of the secondary loops during herniation or shortly after return.

Intestinal morphogenesis is characterized by 3 phases of looping, each with a distinct underlying mechanism. The secondary loops of the small intestine develop according to a highly predictable pattern.

We hypothesize, based on published accounts of malrotations, that the pathology associated with these malformations results from incomplete development of the secondary loops.

This study was undertaken in accordance with the Dutch regulation for the proper use of human tissue for medical research purposes. Only specimens with an intact umbilicus were selected for reconstruction.

Brain development [ 45 ], and the return of the physiological hernia between 9. Specimens of 8—10 weeks development will also be referred to as embryos.

Serial sections were first aligned automatically with the least-squares method and then manually adjusted to account for curvature and rotation of the body axis with the help of photographic, MRI and ultrasound images of age-matched embryos [ 50 ]; Aligned slices were resampled into the Amira mesh-file format.

The intestine, mesentery, vessels and reference structures were segmented manually based on histologically identifiable contours.

The outer muscular layer was used to delineate the esophagus and stomach, and the serosal layer of the intestine was used to delineate the intestinal tract to the transition of the hindgut from an intra- to a retroperitoneal position.

Somites, intersegmental arteries, spinal ganglia, and vertebral bodies were used as landmarks for segmental levels. To describe the precise topographic position of structures, landmarks such as somites, vertebrae, spinal ganglia, and intersegmental arteries were identified.

The exact somite level was deduced from the position of the 7 th intersegmental artery future subclavian artery located between somites 10 and 11 [ 51 — 53 ].

Once vertebral development begins, the 7 th intersegmental artery is found in the loose zone of somite 11 and no longer between somites.

As such, segments 1—7 correspond to C, segments 8—19 to Th, and segments 20—24 to L The meshes for the mesentery were optimized using deformers and sculpting, whereas the intestine and vessels were modeled with Bezier curves.

All structures were modeled proportionally and scaled as indicated. Intestinal length was measured in Cinema4D by assessment of the spline length of the Bezier curves.

The data set s supporting the results of this article is are included within the article and its Additional file 1.

Additional file 1: M, pdf Supplemental Figures. The color codes correspond to those used in the Figures Legend Table. PDF kb.

Competing interests. JHMS performed data acquisition, generated the 3D models and drafted the manuscript.

WHL and LK conceived of the study, and participated in its design and coordination and helped to draft the manuscript.

All authors read and approved the final manuscript. Jelly HM Soffers, Email: ln. Hayelom K. Mekonen, Email: ln.

Eleonore Koehler, Email: ln. Wouter H. National Center for Biotechnology Information , U. BMC Dev Biol. Published online Aug Mekonen , S.

Eleonore Koehler , and Wouter H. Eleonore Koehler. Author information Article notes Copyright and License information Disclaimer.

Corresponding author. Received Oct 30; Accepted Oct This article has been cited by other articles in PMC. Abstract Background It remains unclear to what extent midgut rotation determines human intestinal topography and pathology.

Results We distinguished 3 generations of midgut loops. Electronic supplementary material The online version of this article doi Background Congenital intestinal malrotations are thought to be present in — live births [ 1 ].

Results The pre-herniation period The foregut could first be identified in Carnegie Stage CS 9 embryos 25—27 days post fertilization and the hindgut at CS10 28—30 days.

Open in a separate window. The formation of the midgut week 5 The intestine started to loop ventrally during CS14 33—35 days , with the connection with the vitelline duct at its apex Fig.

Landmarks for the apex of the midgut loop The midgut is that part of the intestine which forms the primary loop.

The herniation period The herniation of the primary midgut loop week 6 Starting in the 5 th week and continuing during the 6 th week, the root of the SMA descended from the level of segment 13 to that of segment 19 corresponding to Th6 and Th12, respectively.

The post-herniation position of the secondary loops The 1 st secondary loop increased substantially in length and continued to expand in a leftward direction caudally of the mesenteric rod.

Development of the colon The colon did not develop secondary loops. Discussion We studied the midgut during its looping and herniation phases of development and distinguished 3 generations of midgut loops.

The midgut as a structural entity The midgut is usually defined as the portion of the gut that is perfused by the SMA and that shows the characteristic features of herniation and rotation [ 8 ].

Primary loop The primary loop encompasses the entire midgut. Secondary loops The small intestinal portion of the primary loop was further divided into secondary loops according to a strict spatiotemporal pattern during the late 6 th and early 7 th week.

Tertiary loops The secondary loops formed additional, tertiary loops after the second half of the 8 th week of development.

What triggers intestinal return? Does the midgut rotate? Implications for malformations By far the best-known malformation of the intestine is malrotation.

Conclusions Intestinal morphogenesis is characterized by 3 phases of looping, each with a distinct underlying mechanism. Methods Specimens This study was undertaken in accordance with the Dutch regulation for the proper use of human tissue for medical research purposes.

Table 1 Reconstructed embryos. Supporting data The data set s supporting the results of this article is are included within the article and its Additional file 1.

Additional file Additional file 1: M, pdf Supplemental Figures. Footnotes Competing interests The authors declare that they have no competing interests.

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