Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity.

Visceral adipose tissue (VAT) encases mesenteric lymphatic vessels and lymph nodes through which lymph is transported from the intestine and mesentery. Whether mesenteric lymphatics contribute to adipose tissue inflammation and metabolism and insulin resistance is unclear. Here we show that obesity is associated with profound and progressive dysfunction of the mesenteric lymphatic system in mice and humans. We find that lymph from mice and humans consuming a high-fat diet (HFD) stimulates lymphatic vessel growth, leading to the formation of highly branched mesenteric lymphatic vessels that 'leak' HFD-lymph into VAT and, thereby, promote insulin resistance. Mesenteric lymphatic dysfunction is regulated by cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-C-VEGF receptor (R)3 signalling. Lymph-targeted inhibition of COX-2 using a glyceride prodrug approach reverses mesenteric lymphatic dysfunction, visceral obesity and inflammation and restores glycaemic control in mice. Targeting obesity-associated mesenteric lymphatic dysfunction thus represents a potential therapeutic option to treat metabolic disease.

Misdiagnosis of appendiceal abscess with intestinal malrotation: A case report.

Here, we report the case of a 75-year-old male with abdominal pain who was admitted to our Emergency Department. Computed tomography (CT) scan revealed torsion of the mesenteric root with fluid surrounding the area. Emergency laparotomy, performed under general anesthesia, revealed appendiceal abscess with intestinal malrotation. Appendicectomy was performed after the torsional mesentery restoration. Antibiotics and other symptomatic treatments were administered postoperatively. The patient recovered well and was discharged one week after surgery. Intestinal malrotation is more common in neonates than in adults. The diagnosis of appendicitis could be further obscured by intestinal malrotation. Therefore, the rare situation of intestinal malrotation and ectopic appendicitis in the abdomen should be considered in cases with an absence of right lower abdominal pain, where preoperative abdominal CT shows mesenteric volvulus and the surrounding intestinal wall is thickened and demonstrating exudation.

Sclerosing Mesenteritis Mimicking IgG4-related Disease.

A 72-year-old man was followed as an outpatient at our hospital for 6 years after surgery for small cell carcinoma of left adrenal gland origin. Follow-up abdominal computed tomography showed a 6-cm mass in the left lower mesentery. The patient underwent open laparotomy. The histological diagnosis was sclerosing mesenteritis. The previous specimens of the left adrenal mass were then re-examined with a microscope, and panniculitis was found around the small cell carcinoma. Both lesions were histologically similar to IgG4-related disease (RD), but they did not completely meet the diagnostic criteria of IgG4-RD clinically or histologically.

Differences in the response to periarterial nerve stimulation or exogenous noradrenaline infusion in the mesenteric vascular bed with the intestinal tract harvested from commonly used rat models of hypertension.

Many hypertensive animal models have been developed and used to elucidate the pathophysiology of hypertension and to develop antihypertensive drugs. Among them, the spontaneous hypertensive rat (SHR), deoxycorticosterone acetate (DOCA)-treated and high salt intake rat (DOCA-salt), and high sodium-fed Dahl salt-sensitive rat (HS) models are commonly used. Multiple studies have been conducted, however, elevation in blood pressure in these models due to the reactivity of adrenergic vasoconstriction has not been well characterized in a centralized experiment. In this study, the pressor responses to periarterial nerve stimulation (PNS) or exogenous noradrenaline (NA) infusion were measured in the isolated mesenteric vascular bed with the intestinal tract to investigate the reactivity of mesenteric adrenergic vasoconstriction. The systemic arterial blood pressure of the hypertensive rat models was uniformly elevated compared with their respective controls. However, the changes in perfusion pressure in the mesenteric vascular bed in response to PNS and exogenous NA infusion were quite different depending on the model. The pressor responses to PNS in SHRs and Dahl S HS rats were significantly higher, and those in DOCA-salt rats were significantly lower than those in the controls. The pressor responses to exogenous NA infusion in SHRs were significantly higher, and those in Dahl S HS rats were significantly lower than those in their respective controls. No difference was observed in the pressor responses to the exogenous NA between the DOCA-salt and sham groups. These results demonstrate that the reactivity of adrenergic vasoconstriction is different for each type of experimental hypertensive model rat.

The Mesentery, Systemic Inflammation, and Crohn's Disease.

Initially thought to be a structure that only provided support to the abdominal contents, the mesentery has now gained special attention in the scientific community. The new approach of studying the mesentery as an individual organ has highlighted its importance in the development of local and systemic inflammatory diseases and its potential role in Crohn's disease. Its topographical relationship with the intestine in the setting of active inflammation and "creeping fat" is possibly one of the most important arguments for including the mesentery as an important factor in the pathogenesis of Crohn's disease. In this review, we discuss the importance of the mesentery from the anatomical and embryological standpoints. We also will summarize data on mesenteric inflammation in patients with Crohn's disease. The significance of the mesentery in systemic inflammatory syndromes will be discussed, and we provide an overview of primary inflammatory disorders of the mesentery. Finally, we discuss surgical approaches for patients requiring resection for Crohn's disease that incorporate mesenteric factors, pointing out recent data suggesting that these have the potential for improving outcomes and reducing disease recurrence.10.1093/ibd/izy201_video1izy201.video15794169491001.

The Mesenteric Fat and Intestinal Muscle Interface: Creeping Fat Influencing Stricture Formation in Crohn's Disease.

Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called "creeping fat") was described as a characteristic feature of Crohn's disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat-mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.

An Unusual Case of Cecal Mesenteric Dedifferentiated Liposarcoma Involving the Ileocolic Artery Resected by Right Hemicolectomy.

BACKGROUND: Colonic mesenteric dedifferentiated liposarcoma is a rare entity. CASE REPORT: A 65-year-old male developed a 6 cm diameter right-side intra-abdominal mesenteric mass. A biopsy of the mass was performed and the pathology diagnosis was a spindle cell neoplasm most consistent with low-grade sarcoma. The mass was found to involve the ileocolic vessels in the mesentery on the right side of the abdomen, and therefore the patient received right hemicolectomy with mesenteric mass resection. Pathology confirmed a dedifferentiated liposarcoma (DDLPS) arising in a well-differentiated liposarcoma/atypical lipomatous tumor with myxoid changes. The tumor cells were positive for MDM2 amplification by fluorescence in situ hybridization. After 6 months of follow-up, our patient showed no sign of recurrence. CONCLUSION: We report an unusual cecal mesenteric DDLPS which was successfully resected by right hemicolectomy. The results suggest that DDLPS should be considered in the differential diagnosis of patients presenting with a spindle cell neoplasm in the mesentery.

Detection of patients at high risk for nonocclusive mesenteric ischemia after cardiovascular surgery.

OBJECTIVES: Nonocclusive mesenteric ischemia (NOMI) is a rare but life-threatening complication after cardiovascular surgery. Early diagnosis and treatment is essential for a chance to cure. The aim of this study is to identify the independent risk factors for NOMI based on the evaluation of 12 cases of NOMI after cardiovascular surgery. METHODS: We retrospectively analyzed 12 patients with NOMI and 674 other patients without NOMI who underwent cardiovascular surgery in our hospital. We reviewed the clinical data on NOMI patients, including their characteristics and the clinical course. In addition, we performed a statistical comparison of each factor from both NOMI and non-NOMI groups to identify the independent risk factors for NOMI. RESULTS: The median duration between the cardiac surgery and the diagnosis of NOMI was 14.0 (10.3-20.3) days. The in-hospital mortality of NOMI patients was 75.0%. Age (p < 0.05), peripheral arterial disease (p < 0.001), postoperative hemodialysis (p < 0.001), intraaortic balloon pump (p < 0.05), norepinephrine (NOE) > 0.10γ (p < 0.0001), percutaneous cardiopulmonary support (p < 0.001), sepsis (p < 0.05), loss of sinus rhythm (p < 0.05), prolonged ventilation (p < 0.0001), and resternotomy for bleeding (p < 0.05) showed significant differences between NOMI and non-NOMI groups. In the multivariate logistic regression model, prolonged ventilation [odds ratio (OR) = 18.1, p < 0.001] and NOE > 0.10 µg/kg/min (OR = 130.0, p < 0.0001) were detected as independent risk factors for NOMI. CONCLUSIONS: We have identified the risk factors for NOMI based on the evaluation of the 12 cases of NOMI after cardiovascular surgery. This result may be useful in predicting NOMI, which is considered difficult in clinical practice. For the patient with suspected of NOMI who has these risk factors, early CT scan and surgical exploration should be performed without delay.

The role of adipose tissue in inflammatory bowel diseases.

PURPOSE OF REVIEW: The occurrence of creeping fat wrapping segments of inflamed gut represents a characteristic yet incompletely understood hallmark of Crohn's disease. Over the last decade, numerous studies have provided a limited understanding of this feature. Still, deciphering the detailed mechanisms and the pathophysiologic relevance of the interplay between creeping fat, barrier function and intestinal inflammation will be the aim of future studies. RECENT FINDINGS: The last 18 months have substantially contributed to this field, starting with an elegant three-dimensional study revealing B cell aggregates around lymphatic vessels embedded in the mesenteric fat, thus bringing back the idea that Crohn's disease might represent a 'lymphatic disease'. Furthermore, studies on a cellular level elucidated the interplay of mesenteric adipocytes, immune cells and intestinal epithelial cells. Last, imaging studies provide evidence indicating that changes depicted by computed tomography within the mesenteric fat compartment rather than of the bowel wall are predictive for the presence of endoscopic lesions. This underlines the impact of mesenteric changes on Crohn's disease activity. SUMMARY: The findings of the last 18 months further contribute to solving the puzzle that will ultimately reveal the role of the mesenteric fat tissue in the control of intestinal immunity and inflammation.

Mesenteric organ lymphatics and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex gastrointestinal disorder and its etiology is unclear yet. Current theory in IBD is focused on genetics, immunity and intestinal microbes. Emerging clinical evidence and experimental results suggest that morphologic abnormalities and dysfunction of mesenteric lymphatics may have potential roles in the pathogenesis and disease course of IBD. In this review, we summarize the findings of specific investigations of the lymphatics and explore its role in IBD.

Etanercept restores vasocontractile sensitivity affected by mesenteric ischemia reperfusion.

BACKGROUND: The aim of the study is to evaluate in vivo and in vitro effects of etanercept, a soluble tumor necrosis factor receptor, on the contractile responses of superior mesenteric artery in an experimental mesenteric ischemia and reperfusion model. MATERIAL AND METHODS: After obtaining animal ethics committee approval, 24 Sprague-Dawley rats were allocated to three groups. Control group (Gr C, n = 6) underwent a sham operation, whereas ischemia/reperfusion and treatment groups underwent 90 min ischemia and 24-h reperfusion (Gr I/R, n = 12; Gr I/R+E, n = 6). The treatment group received 5 mg/kg etanercept intravenously at the beginning of reperfusion. At the end of reperfusion, all animals were sacrificed, and third branch of superior mesenteric artery was dissected for evaluation of contractile responses. In vitro effects of etanercept on vasocontractile responses were also evaluated. The excised ileums were analyzed under light microscope. Two-way analysis of variance following Bonferroni post hoc test was used for evaluation of contractile responses. RESULTS: Endothelin-1 and phenylephrine-mediated vasocontractile sensitivity were found increased in Gr I/R when compared with Gr C. Both intravenous administration and organ bath incubation of etanercept decreased the sensitivity of contractile agents for Gr I/R. Mucosal injury, lamina propria disintegration, and denuded villous tips were observed in Gr I/R, whereas the epithelial injury and the subepithelial edema were found to be milder in Gr I/R+E. CONCLUSIONS: Etanercept can be a promising agent in mesenteric ischemic reperfusion injury as it does not only inhibit inflammation by blocking tumor necrosis factor-α in circulation but also restores vascular contractility during reflow. These findings support an unexplained recuperative effect of drug beyond its anti-inflammatory effects.

Transmesenteric hernia: a rare case of acute abdominal pain in children: a case report and review of the literature.

In this report, we discuss the case of an 11-year old girl presenting with acute abdominal pain caused by gangrene of a large part of the small bowel. During urgent surgical exploration, the cause of gangrene appeared to be herniation of the small bowel through a congenital defect in the mesentery with subsequent strangulation. A resection was performed leaving the patient with only 130 cm of small bowel remaining. Transmesenteric hernia is a rare type of internal herniation consisting of a small congenital defect in the small bowel mesentery through which the intestine can herniate and subsequently become strangulated. We present a case of transmesenteric hernia with disastrous effects and review the literature regarding this rare type of hernia.

Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry.

INTRODUCTION: The paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry. MATERIALS AND METHODS: Mice of C57Bl strain were used in the study. ADP was injected to the vena cava and blood flow was monitored with the use of a laser Doppler flowmeter in the mesentery. Measurements in platelet-depleted mice, mice pretreated with cangrelor, an ADP receptor antagonist, and eptifibatide, a blocker of fibrinogen binding to GPIIbIIIa, were conducted as the proof-of-concept in the performed experiments. Intravital microscopy and ex vivo imaging of organs was performed to identify the sites of aggregate formation resulting from ADP injection. RESULTS: The injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung. CONCLUSIONS: Injection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates.

The mesentery: structure, function, and role in disease.

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.

Printing cancer cells into intact microvascular networks: a model for investigating cancer cell dynamics during angiogenesis.

While cancer cell invasion and metastasis are dependent on cancer cell-stroma, cancer cell-blood vessel, and cancer cell-lymphatic vessel interactions, our understanding of these interactions remain largely unknown. A need exists for physiologically-relevant models that more closely mimic the complexity of cancer cell dynamics in a real tissue environment. The objective of this study was to combine laser-based cell printing and tissue culture methods to create a novel ex vivo model in which cancer cell dynamics can be tracked during angiogenesis in an intact microvascular network. Laser direct-write (LDW) was utilized to reproducibly deposit breast cancer cells (MDA-MB-231 and MCF-7) and fibroblasts into spatially-defined patterns on cultured rat mesenteric tissues. In addition, heterogeneous patterns containing co-printed MDA-MB-231/fibroblasts or MDA-MB-231/MCF-7 cells were generated for fibroblast-directed and collective cell invasion models. Printed cells remained viable and the cells retained the ability to proliferate in serum-rich media conditions. Over a culture period of five days, time-lapse imaging confirmed fibroblast and MDA-MB-231 cell migration within the microvascular networks. Confocal microscopy indicated that printed MDA-MB-231 cells infiltrated the tissue thickness and were capable of interacting with endothelial cells. Angiogenic network growth in tissue areas containing printed cancer cells was characterized by significantly increased capillary sprouting compared to control tissue areas containing no printed cells. Our results establish an innovative ex vivo experimental platform that enables time-lapse evaluation of cancer cell dynamics during angiogenesis within a real microvascular network scenario.

Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock.

PURPOSE: To evaluate whether post-hemorrhagic shock mesenteric lymph (PSML) is involved in cardiac dysfunction induced by hemorrhagic shock. METHODS: The hemorrhagic shock model (40±2 mmHg, 3h) was established in rats of the shock and shock+drainage groups; and PSML drainage was performed from hypotension 1-3h in the shock+drainage rats. Then, the isolated hearts were obtained from the rats for the examination of cardiac function with Langendorff system. Subsequently, the isolated hearts were obtained from normal rats and perfused with PSML or Krebs-Henseleit solution, and the changes of cardiac function were observed. RESULTS: The left ventricular systolic pressure (LVSP) and the maximal rates of LV developed pressure (LVDP) rise and fall (±dP/dt max) in the shock and shock+drainage groups were lower than that of the sham group; otherwise, these indices in the shock+drainage group were higher compared to the shock group. In addition, after isolated hearts obtained from normal rats perfusing with PSML, these cardiac function indices were gradual decline along with the extension of time, such as heart rate, LVSP, ±dP/dt max, etc. CONCLUSION: Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock.