Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching.

During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives--rather than responds to--metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture.

Visceral artery anomalies in patients with Alagille syndrome.

BACKGROUND: Intracranial and pulmonary vascular anomalies are well-known complications and causes of mortality in AGS; however, visceral artery anomalies are less commonly recognized. Herein, we present a retrospective analysis of our experience with pediatric LDLT that focuses on the current problems with and treatments for visceral artery anomalies in AGS after LDLT. METHODS: Between May 2001 and December 2017, 294 LDLTs were performed for 285 pediatric recipients. Of these, 13 LDLTs (4.4%) for 12 AGS patients were performed. We classified the visceral artery anomalies into aneurysms and stenosis. RESULTS: The overall incidence of visceral aneurysm was 2 of 12 recipients (16.7%) and included a SMA aneurysm in one patient and an IPDA aneurysm with a subsequent SPA aneurysm in one patient; the ages of the diagnosis of visceral aneurysm were 16.3, 21.1, and 21.7 y, respectively. An endovascular treatment was performed for a progressive IPDA saccular aneurysm (12.0 × 14.5 × 15.0 mm). The overall incidence of visceral artery stenosis was 7 of 12 recipients (58.3%) and the median age at the diagnosis of visceral artery stenosis was 15.5 y (range 1.7-22.9 y). All 3 AGS patients with RA stenosis suffered from renal dysfunction (eGFR of 51, 78, and 51 mL/min/1.73m2 ). CONCLUSION: The morbidity of visceral artery anomalies is not negligible. The performance of periodic imaging examinations is necessary, even for infants, because it is difficult to detect visceral vascular anomalies in the infant stage.

Venous-derived angioblasts generate organ-specific vessels during zebrafish embryonic development.

Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. Although it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions, the embryonic origins of tissue-specific vessels and the molecular mechanisms regulating their formation are poorly understood. The subintestinal plexus of the zebrafish embryo comprises vessels that vascularize the gut, liver and pancreas and, as such, represents an ideal model in which to investigate the early steps of organ-specific vessel formation. Here, we show that both arterial and venous components of the subintestinal plexus originate from a pool of specialized angioblasts residing in the floor of the posterior cardinal vein (PCV). Using live imaging of zebrafish embryos, in combination with photoconvertable transgenic reporters, we demonstrate that these angioblasts undergo two phases of migration and differentiation. Initially, a subintestinal vein forms and expands ventrally through a Bone Morphogenetic Protein-dependent step of collective migration. Concomitantly, a Vascular Endothelial Growth Factor-dependent shift in the directionality of migration, coupled to the upregulation of arterial markers, is observed, which culminates with the generation of the supraintestinal artery. Together, our results establish the zebrafish subintestinal plexus as an advantageous model for the study of organ-specific vessel development and provide new insights into the molecular mechanisms controlling its formation. More broadly, our findings suggest that PCV-specialized angioblasts contribute not only to the formation of the early trunk vasculature, but also to the establishment of late-forming, tissue-specific vascular beds.

Quantification of fluorescence angiography in a porcine model.

PURPOSE: There is no consensus on how to quantify indocyanine green (ICG) fluorescence angiography. The aim of the present study was to establish and gather validity evidence for a method of quantifying fluorescence angiography, to assess organ perfusion. METHODS: Laparotomy was performed on seven pigs, with two regions of interest (ROIs) marked. ICG and neutron-activated microspheres were administered and the stomach was illuminated in the near-infrared range, parallel to continuous recording of fluorescence signal. Tissue samples from the ROIs were sent for quantification of microspheres to calculate the regional blood flow. A software system was developed to assess the fluorescent recordings quantitatively, and each quantitative parameter was compared with the regional blood flow. The parameter with the strongest correlation was then compared with results from an independently developed algorithm, to evaluate reproducibility. RESULTS: A strong correlation was found between regional blood flow and the slope of the fluorescence curves (ROI I: Pearson r = 0.97, p < 0.001; ROI II: 0.96, p < 0.001) as the normalized slope (ROI I: Pearson r = 0.92, p = 0.004; ROI II: r = 0.96, p = 0.001). There was acceptable correlation of the slope of the curve between two independently developed algorithms (ROI I+II: Pearson r = 0.83, p < 0.001), and good resemblance was found with the Bland-Altman method, with no proportional bias. CONCLUSIONS: Perfusion assessment with quantitative indocyanine green fluorescence angiography is not only feasible but easy to perform with commercially available equipment and readily accessible software.

The natural history of splanchnic artery aneurysms and outcomes after operative intervention.

OBJECTIVE: Splanchnic artery aneurysms (SAAs) are uncommon, and standards for surveillance and intervention are lacking. The goal of this study was to review our 20-year experience with managing SAAs. METHODS: The Research Patient Data Registry at the Massachusetts General Hospital was queried, and all patients with SAAs identified by axial imaging from 1994 to 2014 were included. Aneurysms were stratified into two cohorts: those that underwent early intervention (<6 months after lesion discovery) and those that received surveillance. Primary study end points included aneurysm growth or rupture during surveillance and patient 30-day morbidity or mortality after aneurysm repair. RESULTS: There were 264 SAAs identified in 250 patients. In 166 patients, 176 SAAs (66.6%) were placed into the surveillance cohort; 38 SAAs (21.6%) did not have subsequent axial imaging and were considered lost to follow-up. Mean aneurysm size in the surveillance cohort at first imaging study was 16.28 mm (8-41 mm), and mean surveillance time was 36.1 months (2-155 months); 126 SAAs (91.3%) remained stable in size over time, and 8 SAAs (5.8%) required intervention for aneurysm growth after a mean of 24 months. There were no ruptures in the surveillance cohort. There were 88 SAAs (33.3%) repaired early. Mean size of SAAs that were repaired early was 31.1 mm (10-140 mm). For intact SAAs, 30-day morbidity and mortality rates after repair were 13% and 3%, respectively. In the early repair cohort, 13 SAAs (14.7%) were ruptured at presentation. The 30-day morbidity and mortality rates after rupture were 54% and 8%, respectively. Five ruptured SAAs (38%) were anatomically located in the pancreaticoduodenal arcade. On univariate analysis, pancreaticoduodenal aneurysms were strongly associated with rupture (P = .0002). CONCLUSIONS: Small SAAs (≤25 mm) are not prone to significant expansion and do not require frequent surveillance imaging. Imaging every 3 years for small SAAs is adequate. Aneurysms of the pancreaticoduodenal arcade and gastroduodenal aneurysms are more likely to rupture and therefore warrant a more aggressive interventional approach.

Arterial pseudoaneurysms complicating pancreatitis: literature review.

Arterial pseudoaneurysm formation of visceral arteries as a vascular complication of pancreatitis, either acute or chronic, is an uncommon phenomenon. This review article discusses the incidence, pathophysiology, imaging, treatment strategies, and prognosis of mesenteric pseudoaneurysms complicating pancreatitis.

Multi-phase postmortem CT angiography: recognizing technique-related artefacts and pitfalls.

BACKGROUND AND PURPOSE: Multi-phase postmortem CT angiography (MPMCTA) is increasingly being recognized as a valuable adjunct medicolegal tool to explore the vascular system. Adequate interpretation, however, requires knowledge about the most common technique-related artefacts. The purpose of this study was to identify and index the possible artefacts related to MPMCTA. MATERIAL AND METHODS: An experienced radiologist blinded to all clinical and forensic data retrospectively reviewed 49 MPMCTAs. Each angiographic phase, i.e. arterial, venous and dynamic, was analysed separately to identify phase-specific artefacts based on location and aspect. RESULTS: Incomplete contrast filling of the cerebral venous system was the most commonly encountered artefact, followed by contrast agent layering in the lumen of the thoracic aorta. Enhancement or so-called oedematization of the digestive system mucosa was also frequently observed. CONCLUSION: All MPMCTA artefacts observed and described here are reproducible and easily identifiable. Knowledge about these artefacts is important to avoid misinterpreting them as pathological findings.

Long-term results of surgical treatment of aneurysms of digestive arteries.

BACKGROUND: The aim of this study was to document the long-term results of open surgical treatment of aneurysms of the digestive arteries. METHODS: Between January 2000 and March 2010, 60 patients were operated on for 78 aneurysms of the digestive arteries at our institution. The mean age of patients was 61 years (31-84 years). The average lesion diameter was 33 mm (range 10-90 mm). Topographic distribution involved the coeliac trunk in 23 cases (30%), hepatic artery in 20 (26%), splenic artery in 19 (24%), superior mesenteric artery in 11 (14%), gastroduodenal artery in 3 (4%), and pancreaticoduodenal arteries in 2 (3%). Twenty patients (33%) were symptomatic, 1 of whom presented with aneurysmal rupture (1.7%). Follow-up was prospective and an actuarial analysis was carried out. Only 3 patients (5%) were lost to follow-up. RESULTS: Hospital mortality was 1.7% (upper gastrointestinal bleeding from gastric metastases of a kidney cancer). Postoperative complications were mainly respiratory (18%), digestive (18%), and renal (13%). Five reintervention procedures (8%) were necessary: 2 for colonic ischemia; 1 for intestinal bleeding; 1 for secondary graft infection due to peritonitis; and 1 for drainage of an acute pancreatitis. The average follow-up was 42 months (range 1-120 months). The actuarial survival rates were 98% at 1 month and 1 year, and 97% at 5 and 10 years, respectively. One late death occurred at 22 months (bronchopulmonary cancer). Three late reinterventions were carried out: 2 re-establishments of digestive continuity and 1 embolization for a recurrent aneurysm 7 years after the initial operation. The primary patency rate of the revascularizations was 98% at 1 month and 1 year, and 95% at 5 and 10 years. The rates of indemnity of restenosis or thrombosis were 98% at 1 month and 1 year, and 95% and 93% to 5 and 10 years, respectively. The rates of freedom of reintervention on bypasses were 98% at 1 month and 1 and 5 years, and 97% at 10 years. CONCLUSION: Open surgical treatment of aneurysms of the digestive arteries offers excellent long-term results in terms of patency. It is with these late results that endovascular techniques will have to be compared to define the best therapeutic strategy.

Cold-stress induced formation of calcium and phosphorous rich chloragocyte granules (chloragosomes) in the earthworm Eisenia fetida.

The cytochemical and functional characteristics of chloragocytes of both 'control' and cold-stressed Eisenia fetida were examined. Flow cytometry revealed the heterogeneity of chloragocytes: the first group was characterized by low, the second one by high acid phosphatase (AcP) content. In 'control' animals the former, in cold-stressed ones the latter type were the dominant form. The elevated AcP-activity correlated with the accumulation of autophagic vacuoles (AVs) in chloragocytes. Both AVs and all small chloragosomes showed high AcP activity, while most of the large chloragosomes did not display any. Most 'control' granules (0.75-1.25 µm) contained high amounts of Ca and P, with less and variable quantities of S, Cl, K, Fe and Zn. Small chloragosomes with low Ca and P concentrations were seldom found. In cold-stressed animals the number of small granules (0.25-0.75 µm) increased up to 40% of total population. Their Ca and P contents were significantly lower; S and Fe concentrations were higher than those of large chloragosomes (1.0-1.5 µm). Our results prove that the formation and elemental composition of chloragosomes can be influenced by environmental stressors and suggest that the mature chloragosomes are tertiary lysosomes and their formation is coupled to autophagocytosis.

Diagnostic value of multi-slice spiral CT (MSCT) combined with digestive tract angiography in gastric fundus cardia carcinoma.

PURPOSE: To evaluate the diagnostic value of multi-slice spiral CT (MSCT) combined with digestive tract angiography in patients with gastric fundus cardia carcinoma. METHODS: A total of 185 patients with suspected gastric fundus cardia carcinoma admitted in our hospital were collected. Among them, 93 patients were examined with MSCT combined with digestive tract angiography and were enrolled in the research group. Another 92 patients examined by MSCT alone comprised the control group. The diagnostic value of MSCT combined with digestive tract angiography in patients with gastric fundus cardia carcinoma was investigated. 185 patients were diagnosed by pathological examination and 166 had gastric fundus cardia carcinoma, with 84 patients in the research group, and 84 patients in the control group. Fifty nine patients with gastric fundus cardia carcinoma in the control group were diagnosed by MSCT. RESULTS: There were significant differences compared with pathological diagnosis (p<0.05). Eighty-two patients with gastric fundus cardia carcinoma in the research group were diagnosed by MSCT combined with digestive tract angiography. There were no significant differences compared with pathological diagnosis (p>0.05). Sensitivity, specificity and accuracy of the research group were significantly higher than those of the control group (p<0.05). The detectable rate in imaging results of the research group was higher than that of the control group (p<0.05). CONCLUSION: MSCT combined with digestive tract angiography is more accurate than single MSCT in the diagnosis of gastric fundus cardia carcinoma, which can effectively reduce the misdiagnosis and missed diagnosis and is worthy of clinical promotion.

Regional blood-flow changes during 72-hour avoidance schedules in the monkey.

Systemic and regional blood-flow measurements were made in five restrained monkeys before and during 72 hours of continuous work on an avoidance schedule. Systemic arterial pressures were elevated throughout the stress, initially owing to an increase in cardiac output, and after 72 hours owing to an increase in total peripheral resistance. Changes in the resistance in skeletal muscle blood vessels were closely related to these changes in total peripheral resistance.

Rosai-Dorfman Disease of the Digestive System-Beware Vasculopathy: A Clinicopathologic Analysis.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation that occurs in nodal and extranodal sites. Rare examples of the disease involving the digestive system have been described. To characterize the digestive tract manifestations of this disease, 12 specimens from 11 patients with extranodal RDD affecting the digestive organs were analyzed. Hematoxylin and eosin sections and available immunohistochemical stains were reviewed, and the clinical information was obtained from patients' electronic or submitted records. Eight patients were female and 3 male (median age, 65 y; range, 17 to 76 y). Abdominal pain was the most frequent symptom. Six patients had an associated immunologic or malignant disease. Nine lesions arose in the gastrointestinal tract (1 involving the appendix, 2 right colon, 6 left colon), 2 in the pancreas, and 1 in the liver. Two patients had the coexistent nodal disease, and 1 had bone and soft-tissue involvement. The lesions were generally composed of polygonal to spindle-shaped histiocytes with eosinophilic to clear cytoplasm admixed with lymphoplasmacytic cells. The inflammatory cells formed lymphoid aggregates in 7 cases and included focally scattered or small collections of neutrophils in 6 cases. Fibrosis was variable, and 4 cases had a storiform pattern. Vasculopathy in the form of a thickened capillary wall, medium-sized arterial wall infiltration by lesional and inflammatory cells and phlebitis was seen in 10, 5, and 2 cases, respectively. All cases were reactive for S100-protein. Of the 5 patients with follow-up, 1 developed immunoglobulin A nephropathy and died of renal failure.

Artemin is a vascular-derived neurotropic factor for developing sympathetic neurons.

Artemin (ARTN) is a member of the GDNF family of ligands and signals through the Ret/GFRalpha3 receptor complex. Characterization of ARTN- and GFRalpha3-deficient mice revealed similar abnormalities in the migration and axonal projection pattern of the entire sympathetic nervous system. This resulted in abnormal innervation of target tissues and consequent cell death due to deficiencies of target-derived neurotrophic support. ARTN is expressed along blood vessels and in cells nearby to sympathetic axonal projections. In the developing vasculature, ARTN is expressed in smooth muscle cells of the vessels, and it acts as a guidance factor that encourages sympathetic fibers to follow blood vessels as they project toward their final target tissues. The chemoattractive properties of ARTN were confirmed by the demonstration that sympathetic neuroblasts migrate and project axons toward ARTN-soaked beads implanted into mouse embryos.

Vascular lesions of the gastrointestinal tract.

Classification of vascular abnormalities of the gastrointestinal tract on the basis of anatomy and pathophysiology has recently been suggested. Angiodysplasia, an example of an arteriovenous lesion, may cause either acute or chronic bleeding. Diagnosis may be difficult. High-quality standard endoscopy, capsule endoscopy, and double-balloon enteroscopy are most efficacious. Therapy using argon plasma coagulation is currently preferred. Pharmacological therapy has been employed, but a final conclusion about its efficacy cannot yet be drawn. Dieulafoy lesion, an arterial type of vascular abnormality, is rare but serious. It can be responsible for severe haemorrhage. Mechanical endoscopic methods are the most efficacious. Gastric antral vascular ectasia (GAVE), a capillary lesion, can be safely biopsied; it coincides with several diseases (including liver cirrhosis), may cause chronic iron-deficiency anaemia, and is best treated by argon plasma coagulation. Haemangiomas, benign neoplastic lesions, usually occur as part of other specific syndromes; they are difficult to manage due to the multiplicity and size of the lesions.

The patient with circulatory shock: to feed or not to feed?

Controversy continues to surround the appropriate form and timing of nutrition support for the patient with circulatory shock. Clinical studies have demonstrated improvements in outcome with the administration of enteral nutrition to critically ill patients; however, the provision of enteral nutrition to critically ill patients with ongoing shock remains controversial. This article reviews gut perfusion during normal states and during circulatory shock as well as alterations in perfusion when enteral feeding is provided. Pharmaconutrients studied during ischemia and reperfusion are discussed.

[Paradoxical embolism and ischemia of the digestive tract]. / Embolie paradoxale et ischémie digestive.

The digestive tract is an uncommon location of acute ischemia, especially when caused paradoxical embolism. We report the case of a 69-year-old patient initially hospitalized for a acute ischemia of the upper limb. Physical examination and complementary tests enabled the diagnosis of paradoxical embolism with bilateral pulmonary embolism leading to elevated pressure in the pulmonary arteries, which opened the oval foramen. The patient also presented ischemia involving the digestive trunks, the upper limb and the kidneys. Rapid diagnosis is a major challenge in this condition controlling the prognosis of this uncommon disease.

Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor.

We have developed a rat model of ischemic bowel necrosis associated with shock by injection of platelet-activating factor (PAF) or a combination of PAF and endotoxin. Recent investigations have shown that tumor necrosis factor (TNF) also induces shock and necrosis of the gastrointestinal tract. The morphological changes of TNF-induced bowel lesions are indistinguishable from those caused by PAF. The mechanism of TNF-induced bowel necrosis is unclear. In the present study, we have shown that (a) TNF caused PAF production in bowel tissue; (b) the effects of TNF and LPS on PAF production in the intestine are additive; (c) TNF and LPS are synergistic in inducing bowel necrosis; and (d) TNF-induced bowel necrosis is due to PAF release and can be prevented by pretreatment with PAF antagonists.

Contribution of the pancreas to circulating somatostatin-like immunoreactivity in the normal dog.

These studies were performed to assess the contribution of the pancreas to the somatostatin-like immunoreactivity (SLI) circulating in arterial and portal venous plasma. Basal SLI concentrations in arterial, pancreatic venous, and portal venous plasma were 95 +/- 9, 277 +/- 32, and 130 +/- 12 pg/ml, (means +/- SEM), respectively. Measurement of pancreatic and portal venous blood flow (5 +/- 1 vs. 365 +/- 46 ml/min) and hematocrit allowed calculation of net, base-line SLI output from the right lobe of the pancreas (521 +/- 104 pg/min) and from the gastrointestinal tract (8,088 +/- 1,487 pg/min), which suggested that the contribution of the pancreas to circulating SLI was minor when the D cells were not stimulated. To stimulate the secretion of SLI from both pancreatic and nonpancreatic sources, isoproterenol, a beta-adrenergic agonist, was infused intravenously for 1 h into six anesthetized dogs. Arterial SLI increased by 52 +/- 9 pg/ml; superior pancreatico-duodenal venous SLI increased by 380 +/- 95 pg/ml; portal venous SLI increased by 134 +/- 14 pg/ml. Pancreatic venous blood flow remained unchanged at 5 +/- 1 ml/min, but portal venous blood flow increased to 522 +/- 62 ml/min. SLI output from the right lobe of the pancreas increased by 684 +/- 227 pg/min and that from the gastrointestinal tract increased by 23,911 +/- 3,197 pg/min, again suggesting that the pancreas was a minor source of circulating SLI even when the D cells were stimulated. We conclude that the measurement of arterial-venous SLI concentrations, in the absence of measurements of organ blood flow, can give a false impression of the organ's contributions of circulating SLI. To verify that the contribution of the pancreas was negligible, six dogs received an acute pancreatectomy and then an intravenous infusion of isoproterenol at the same rate. In these dogs, both the base-line level of SLI in arterial plasma (109 +/- 12 pg/ml) and the increment during isoproterenol (56 +/- 8 pg/ml) were similar to those of normal dogs. Likewise, in pancreatectomized dogs both the base-line level of SLI in portal venous plasma (129 +/- 16 pg/ml) and the increment during isoproterenol (174 +/- 34 pg/ml) were similar to those of normal dogs. We conclude that, in normal dogs, the pancreas makes a negligible contribution to the basal and stimulated level of SLI in arterial and portal venous plasma and therefore that these levels should not be used as an index of secretory activity of the pancreatic D cells.

Blunt abdominal trauma: current imaging techniques and CT findings in patients with solid organ, bowel, and mesenteric injury.

Imaging plays a critical role in the evaluation of patients with blunt abdominal trauma. In most institutions, computed tomography (CT) is the modality of choice when evaluating such patients. The purpose of this review is to highlight current techniques in trauma imaging and to review CT findings associated with solid organ, bowel, mesenteric, and diaphragmatic injury. In particular, emphasis is placed on the use of multidetector CT technology (MDCT), especially 64-row detector CT. The role of various techniques, including the use of oral and intravenous contrast, as well as the potential benefit of delayed imaging, is discussed.