Mesenteric Vessels Research Articles

Imaging of the Inferior Mesenteric Vasculature.

The inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) supply and drain blood from the distal colon and rectum, respectively. Routinely imaged at cross-sectional imaging of the abdomen and pelvis, these vessels play a vital role in gastrointestinal tract health but may be neglected due to their diminutive caliber relative to other mesenteric vessels and potential lack of inclusion in routine search patterns. The authors describe and illustrate normal and abnormal appearances of the IMA and IMV and findings that are diagnostic of primary vascular abnormalities or can offer diagnostic clues. After the embryologic features, normal anatomy, and anatomic variants of the IMA and IMV are reviewed, various manifestations of IMA and IMV abnormalities, such as aneurysm and pseudoaneurysm, stenosis, occlusion, dissection, hemorrhage, arteriovenous malformations and fistulas, tumoral invasion, vasculitis, and perivascular lymphatic dilatation, are explored with use of case examples. The role of the IMA and IMV as collateral vasculature, including the clinical scenarios of superior mesenteric arterial occlusion, aortic endoleak, and portosystemic venous shunt, are discussed. Finally, diagnostic clues that the inferior mesenteric vessels and adjacent soft tissues can provide, including mesenteric venous gas, compression or displacement from bowel volvulus or internal hernias, lymphadenopathy, and venous flow artifacts, are highlighted. The authors provide a comprehensive reference for radiologists who evaluate the IMA and IMV on cross-sectional images and shine a spotlight on these neglected but important vessels. ©RSNA, 2024 Supplemental material is available for this article.

Clinical features, imaging findings, and outcomes of acute abdominal pain in systemic lupus erythematosus: comparing mesenteric vasculitis, non-mesenteric vasculitis, and surgical conditions.

To determine the spectrum, clinical features and outcomes in systemic lupus erythematosus (SLE) patients with acute abdominal pain (AAP). Medical records of SLE patients in a lupus cohort from January 1987 to June 2023 were reviewed. Patients with AAP requiring hospitalization were identified and categorized into 3 groups: lupus mesenteric vasculitis (LMV), non-LMV, and surgical AAP. Each AAP episode represented one patient. Of 1,538 patients in the cohort, 62 (4.03%) had 93 episodes of AAP. After exclusion, 31 patients had 39 LMV episodes, and 30 had 40 non-LMV episodes (19 due to surgical AAP). Seventy-six of the 79 AAP episodes (96.20%) were in females, with a mean ± SD age and median (IQR) disease duration of 36.76 ± 13.60 years and 6 (2, 9) years, respectively. Patients in the LMV group had more fever, nausea and vomiting, and diarrhea than those in the non-LMV group. They also had more small bowel involvement, bowel wall thickening, target water enhancement signs, mesenteric vessels engorgement and mesenteric fat cloudiness, and higher SLE disease activity. These differences were more pronounced when compared to the surgical AAP group. Treatment with corticosteroids and immunosuppressive drugs gave favorable outcomes in the LMV group. Two of 40 (5.00%) non-LMV AAP patients died, of which 1 (5.26%) was in the surgical AAP group. LMV was common among SLE patients admitted for AAP. LMV usually presented with fever, gastrointestinal dysmotility symptoms, diffused abdominal pain, together with evidence of active disease. Localized abdominal pain with peritoneal signs favored surgical AAP. Key Points • Lupus mesenteric vasculitis is common among SLE patients presenting with acute abdominal pain. Its presence often associates with gastrointestinal symptoms together with other clinical manifestations of SLE • The signs in abdominal computed tomography findings are not specific and could be observed in other causes of abdominal pain in SLE. Interpretation of these signs should be cautionary and accompanied by history taking and physical abdominal findings • Treatment of lupus mesenteric vasculitis with corticosteroids alone, or in combination with immunosuppressive drugs, usually results in good outcomes.

Endovascular Treatment of Complex Aorto-Iliac Atherosclerotic Occlusive Disease With Chimney Covered Endovascular Reconstruction of Aortic Bifurcation.

Treatment of atherosclerotic occlusive disease of the infrarenal aorta poses several challenges. Traditionally, open surgery has been the preferred method of treatment in standard risk patients, although, it is burdened by high morbidity and mortality. There are many classifications to establish the patient risk for surgery. Among the most common is the American College of Cardiology (ACC)/American Heart Association (AHA) classification. ACC/AHA high-risk patients benefit from the increase in endovascular technology and skills. The treatment modality of atherosclerotic aortic disease has shifted towards a minimally invasive approach, including kissing stents, covered endovascular reconstruction of the aortic bifurcation (CERAB) and, aorto-uniiliac stent grafts. When there is an involvement of vital branches such as the inferior mesenteric (with concomitant occluded superior mesenteric artery) or the renal arteries, Chimney- CERAB technique has been successfully utilized to overcome this challenge. We present three patients with aortoiliac occlusive disease (AIOD) successfully treated with the chimney- CERAB technique to preserve a large inferior mesenteric artery in the setting of occlusion/near occlusion of the other mesenteric vessels.

Assessing anatomical variations of the superior mesenteric artery via three-dimensional CT angiography and laparoscopic right hemicolectomy: a retrospective observational study.

This study aimed to analyse the anatomical relationships and differences between the superior mesenteric vessels and their branches by reviewing a laparoscopic right hemicolectomy surgery video and comparing it with preoperative three-dimensional computed tomography (3D-CT) angiography and to verify the accuracy of 3D-CT vascular reconstruction techniques. Surgical videos and preoperative imaging data of 52 patients undergoing laparoscopic right hemicolectomy were analysed to observe and summarize the probability of occurrence and adjacency of superior mesenteric vascular branches, and the lengths of specific sites of their branches were measured using the above two methods. Preoperative CT images and surgical video showed that the ileocolic artery (ICA) was present in 98.1% (51/52) and the ileocolic vein (ICV) was present in 100% (52/52), and ICA was present in 13.7% (7/51) of the ICV directly anteriorly, 13.7% (7/51) anteriorly superiorly, 3.9% (2/51) anteriorly inferiorly, 11.8% (6/51) directly posteriorly, 37.2% (19/51) post superiorly, and 19.7% (10/51) posteriorly inferiorly. In the surgical video, the probability of presence of the right colic artery (RCA) was 21.2% (11/52). On CT images, the RCA was present in 10 patients. The length of the origin of the middle colic artery (MCA) from its bifurcations was 2.33 ± 0.87 cm measured intraoperatively using a sterile isometric filament, and the length measured using 3D-CT vascular reconstruction was 2.36 ± 0.91 cm; the difference was not statistically significant (P = 0.348). The length of the MCA and ICA initiation points was 3.22 ± 0.75 cm measured intraoperatively using sterile isometric filaments and 3.36 ± 0.72 cm measured using 3D-CT vascular reconstruction, which was a statistically significant difference (P < 0.001). 3D-CT vascular reconstruction can accurately predict the vessels related to right hemicolectomy in most cases. It is an important method for preoperative prediction of superior mesenteric vessels, which can guide surgeons in the intraoperative vessel identification.

Intraoperative indocyanine green fluorescence for precise resection of nonocclusive mesenteric ischemia: a case report and diagnostic considerations based on pathology findings

BackgroundNonocclusive mesenteric ischemia (NOMI) is characterized by intestinal ischemia caused by spasms in the peripheral intestinal vessels without organic obstruction in the main mesenteric vessels. NOMI can be fatal in case of delayed diagnosis and treatment. Although the use of indocyanine green (ICG) fluorescence in assessing intestinal viability during NOMI surgery is well recognized, there is a paucity of reported cases using this technique. Herein, we present a case of NOMI that was successfully managed through accurate diagnosis and resection of the ischemic intestines guided by ICG fluorescence.Case presentationAn 81-year-old man presented with abdominal pain. Contrast-enhanced computed tomography revealed intrahepatic portal vein gas, superior mesenteric vein gas, and terminal ileal edema. Considering these findings, the patient was diagnosed with NOMI and emergency surgery was performed. Intestinal edema was observed 30 cm upstream of the terminal ileum without serosal discoloration. ICG fluorescence revealed areas of normal perfusion as well as mild and moderate hypoperfusion. The small bowel, including the hypoperfusion area, was resected. As no clinical signs of residual bowel ischemia were observed during the postoperative course, a second-look operation was deemed unnecessary. Intraoperative ICG fluorescence and histopathological findings indicated mucosal edema in the mildly hypoperfused area and mucosal necrosis in the moderately hypoperfused area.ConclusionsThis case highlights the use of intraoperative ICG fluorescence in the disease. ICG fluorescence is invaluable in assessing the extent of bowel ischemia and guiding precise resection. Thus, future efforts should focus on identifying accumulation of cases and quantification of ICG fluorescence intensity to further improve diagnostic performance.

Robot-Assisted Pancreaticoduodenectomy Using the Anterior Superior Mesenteric Artery-First Approach for Pancreatic Cancer.

The superior mesenteric artery (SMA)-first approach for pancreatic cancer (PC) is common surgical technique in pancreaticoduodenectomy. To date, few studies have reported SMA-first approach in robot-assisted pancreaticoduodenectomy (RPD). Herein, we present the anterior SMA-first approach for PC during RPD. A 75-year-old man with resectable PC underwent RPD after neoadjuvant chemotherapy. As pancreatic head tumor contacted with the superior mesenteric vein (SMV), the anterior SMA approach was applied. After the mesenteric Kocher maneuver, the jejunum was divided and the left side of the SMA was dissected. Subsequently, the anterior plane of the SMA was dissected. Following the division of branches from the mesenteric vessels, the SMA was taped, and the circumferential dissection around the SMA was performed to detach the pancreatic neck from the SMA completely. Finally, the dissection between the SMV and the tumor was performed under vascular control to remove the specimen. The anterior SMA-first approach can be optional in patients with PC undergoing RPD. This unique approach allows for the circumferential dissection around the SMA during RPD.

Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy.

Intestinal ischemia-reperfusion (I/R) injury is an acute condition characterized by tissue damage resulting from restricted blood flow to the mesenteric vessels, leading to both local and systemic pathologies with a poor prognosis. Both ischemia and reperfusion trigger a series of cellular and molecular responses, with inflammatory cells serving as key regulators of the pathology. These interactions with the ischemic endothelium are mediated by multiple adhesion receptors. Several animal models have been established to mimic this pathology and investigate the involved molecular pathways. In this study, a microsurgical model of I/R injury is combined with intravital microscopy to visualize leukocyte rolling, adhesion, and neutrophil extracellular trap (NET) formation. This model is applied to transgenic mice deficient in endothelial PAR1 (F2r) to assess the impact of PAR1 on leukocyte rolling and NET formation 1 h after ischemia and immediately following reperfusion. In vivo, Acridine Orange leukocyte staining was employed, and NETs were visualized using a nucleic acid stain. Interestingly, reduced leukocyte adhesion and NET formation were observed in mice lacking the endothelial PAR1 receptor. This model enables the in vivo analysis of key regulators involved in I/R injury.

Performance of Prenatal Ultrasound Screening for the Relative Positioning of Mesenteric Vessels.

Abnormal relative positioning of the superior mesenteric artery (SMA) and vein (SMV) can lead to intestinal malrotation that predisposes to midgut volvulus. The aim of this study was to assess the prenatal ultrasound ability to visualize the relative position of SMA and SMV in normal pregnancies. Prospective cohort study performed in Montpellier University Hospital Centre, including 80 fetuses during routine 3rd trimester ultrasound scan. For each fetus included, the relative position of the vessels on an axial image was defined as SMV on the right, forward, or on the left of SMA. Doppler imaging was additionally used if necessary. Data were compared to the neonatal abdominal scans performed by pediatric radiologist. The superior mesenteric vessels were identified in 79 fetuses. Prenatal findings showed a usual relative position of the vessels, that is, the vein on the right of the artery, in 96.2%. In 2 cases, the vein was strictly in front of the artery, and in 1 case, the vein was on the left side of the artery. Seventy-four neonates were examined and comparison with prenatal finding showed a perfect agreement (Kappa coefficient of 100%). An intestinal malrotation was postnatally diagnosed corresponding to the case where vein was on the left side of the artery. This study showed that the relative position of the SMA and SMV could be assessed using ultrasound prenatal examination with a perfect agreement with postnatal findings. In case of abnormal vessels positioning more examinations should be promote including prenatal MRI and postnatal conventional radiologic examinations to confirm intestinal malrotation.

Vγ6/Vδ1+ γδ T cells protect from angiotensin II effects on blood pressure and endothelial function in mice.

γδ T cells mediate angiotensin II (AngII)-induced hypertension and vascular injury. γδ T cells expressing specific T-cell receptor (TCR) variable (V) γ chains develop in several waves in the thymus and migrate to specific or diverse tissues. We hypothesized that γδ T cells expressing specific Vγ subtypes in perivascular tissue mediate AngII hypertensive effects. C57BL/6J male mice were infused or not with AngII (490 ng/kg/min, subcutaneously) for 14 days. γδ T-cell Vγ subtypes were profiled by flow cytometry in the spleen, descending thoracic aorta with adherent perivascular adipose tissue (DTAo/PVAT) and mesenteric vessels (MV)/PVAT. Other sets of AngII-infused mice were injected with control or specific anti-Vγ6 or Vγ4 antibodies. Blood pressure (BP) was determined by telemetry, and mesenteric artery function and remodeling by pressurized myography. Vγ6/Vδ1+ γδ T cells represented more than 50% of the γδ T-cell Vγ subtypes in DTAo/PVAT and MV/PVAT, whereas Vγ1/2+, Vγ4+ and Vγ6/Vδ1+ γδ T cells were the most abundant Vγ subtypes in the spleen. The frequency of Vγ6/Vδ1+ γδ T cells was increased at least 1.5-fold in the spleen and DTAo/PVAT, and tended to increase in MV/PVAT by AngII. A majority of Vγ6/Vδ1+ γδ T cells were activated in perivascular tissues. Vγ6/Vδ1+ γδ T-cell neutralization caused a steeper BP elevation and greater mesenteric artery endothelial dysfunction in mice infused with AngII. This was associated with more than three-fold increase in activated Vγ6/Vδ1- γδ T cells in perivascular tissues. Depletion of Vγ4+ γδ T cells did not alter AngII detrimental effects. Vγ6/Vδ1+ γδ T cells reduce the BP elevation and endothelial dysfunction induced by AngII infusion.

Abstract 32: Vγ6 + γδ T cells protect against angiotensin II-induced hypertension and vascular injury in male mice

Background: γδ T cells mediate angiotensin II (AngII)-induced blood pressure (BP) elevation, vascular injury and activated T cell infiltration in mesenteric vessels with adherent perivascular adipose tissue (MV/PVAT). γδ T cells expressing specific T cell receptor (TCR) variable (V) chain γ develop in several waves in the thymus and migrate to diverse tissues. We hypothesized that γδ T cells expressing specific Vγ subtypes in perivascular tissue are implicated in AngII detrimental hypertensive effects. Methods: C57BL/6J male mice were infused or not with AngII (490 ng/kg/min, SC) for 14 days. Vγ1 and Vγ2 (Vγ1/2) + , Vγ4 + , Vγ5 + , Vγ6 + , and Vγ7 + γδ T cell frequencies and T cell phenotypes were determined by flow cytometry in the spleen, descending thoracic aorta (DTAo)/PVAT, and MV/PVAT (n=7-13). Other sets of AngII-infused mice were injected with control or anti-Vγ6 (n=7-12) or Vγ4 antibodies (n=5-8). BP was determined by telemetry, mesenteric artery (MA) function and remodeling by pressurized myography, and T cell phenotypes by flow cytometry. Results: In DTAo/PVAT and MV/PVAT, respectively, 43±5% and 51%±6% of γδ T cells were Vγ6 + , and 17±2% and 23±4% Vγ4 + , whereas in the spleen, 36±2% of the γδ T cells were Vγ1/2 + , 32±1% Vγ4 + and 24±1% Vγ6 + . AngII increased the frequency of Vγ6 + γδ T cells in the spleen (0.8±0.1 vs 0.5±0.0% of CD3, P &lt;0.001) and DTAo/PVAT (5.9±0.8 vs 3.6±0.5% of CD3, P &lt;0.05), and tended to increase their frequency in MV/PVAT. The majority of Vγ6 + γδ T cells were activated (CD69 + ) in DTAo/PVAT (75±5%) and MV/PVAT (84±2%). Vγ6 + γδ T cell depletion caused a steeper BP elevation ( P &lt;0.05) and worsened MA endothelial dysfunction (maximal acetylcholine relaxation response: 28±3 vs 55±8%, P &lt;0.05) in mice infused with AngII. This was associated with increased CD69 + non-Vγ6 + γδ T cells in DTAo/PVAT (3.0±0.7 vs 0.8±0.4% of CD3, P &lt;0.01) and MV/PVAT (15.2±2.6 vs 4.9±1.0% of CD3, P &lt;0.01). Depletion of Vγ4 + γδ T cells in perivascular tissues, did not alter the AngII detrimental effects. Conclusions: Vγ6 + γδ T cells are the most abundant γδ T cell Vγ subtype in perivascular tissues. AngII increased Vγ6 + γδ T cells in the spleen and perivascular tissue. Vγ6 + γδ T cell depletion in AngII-infused mice induced a steeper BP elevation, worsened MA endothelial dysfunction, and activated non-Vγ6 + γδ T cells. Vg6 + γδ T cells may play a protective role in AngII-induced hypertension and vascular injury.

Laparoscopic Left Side Duodenum Adenocarcinoma Resection (III-IV Segment): A Step-By-Step Surgical Technique.

Nonampullary duodenal adenocarcinoma (NDA) accounts for approximately 5% of all gastrointestinal cancers. Complete surgical resection (R0) with regional draining lymph node removal is mandatory as treatment to potentially cure nonampullary duodenal cancer or to achieve long-term survival. According to existing literature, minimally invasive surgery has been reported to be safe and oncologically equivalent in pancreaticoduodenectomy for pancreatic and duodenal cancer. We describe a fully laparoscopic approach for the left-side adenocarcinoma of the duodenum "left-side" is defined with reference to the mesenteric vessels (III-IV segment). For the first time in literature, this multimedia paper describes a fully laparoscopic complete resection (R0) of the left side of the duodenum (III-IV segment) with locoregional lymph node resection. The main steps of the procedure are described using the concept of the critical view of safety. Reconstruction of intestinal continuity was ensured by full intracorporeal anastomosis. Through the tips and indications presented in this article, we supply a guide to the minimally invasive approach and increase operating surgeons' familiarity with such a complex procedure.

Changes in microcirculation of small intestine end-to-end anastomoses in an experimental model

IntroductionSufficient perfusion is essential for a safe intestinal anastomosis. Impaired microcirculation may lead to increased bacterial translocation and anastomosis insufficiency. Thus, it is important to estimate well the optimal distance of the anastomosis line from the last mesenterial vessel. However, it is still empiric. In this experiment the aim was to investigate the intestinal microcirculation at various distances from the anastomosis in a pig model. Materials and methodsOn 8 anesthetized pigs paramedian laparotomy and end-to-end jejuno-jejunostomy were performed. Using Cytocam-IDF camera, microcirculatory recordings were taken before surgery at the planned suture line, and 1 to 3 mesenterial vessel mural trunk distance from it, and at the same sites 15 and 120 min after anastomosis completion. After the microcirculation monitoring, anastomosed and intact bowel segments were removed to test tensile strength. ResultsThe proportion and the density of the perfused vessels decreased significantly after anastomosis completion. The perfusion rate increased gradually distal from the anastomosis, and after 120 min these values seemed to be normalized. Anastomosed bowels had significantly lower maximal tensile strength and higher slope of tensile strength curves than intact controls. ConclusionAlterations in microcirculation and tensile strength were observed. After completing the anastomosis, the improvement in perfusion increased gradually away from the wound edge. The IDF device was useful to monitor intestinal microcirculation providing data to estimate better the optimal distance of the anastomosis from the last order mesenteric vessel.

Surgical treatment of right colon cancer

The study aimed to perform a systematic review of the literature on surgical treatment for right colon cancer (RCC) with complete mesocolic excision (CME) and D2/D3 lymph node dissection (LND). Material and Methods. A literature review was performed for studies published between 2013 and 2023 by the online resources from the official Web sites of the societies/panels and PubMed database. Sources included guidelines, meta-analyses, randomized and nonrandomized clinical studies, guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network, Russian clinical guidelines. Results. CME significantly improved both immediate and long-term treatment results, which was confirmed by numerous meta-analyses. The extent of LND remains one of the most controversial issues in RCC. For many Asian surgeons, D3 LND is the standard procedure for the treatment of RCC, whereas the European approach is more conservative and apical lymph node dissection is not mandatory. There are also large differences in understanding the extent of D3 LND in RCC. Most surgeons understand this term as dissection of adipose tissue along the anterior and lateral surface of the superior mesenteric vein, however, there are authors who perform circular dissection along the superior mesenteric vessels, considering this extent of surgery to be the most radical. Conclusion. It is necessary to standardize methods and effective criteria for quality control of CME for RCC and LND. In this case, external independent assessment of the quality of surgical intervention is important. There is also currently a growing number of studies in which intraoperative fluorescence imaging makes it possible to better visualize the location of the apical lymph nodes and individualize LND.

Laparoscopic right radical hemicolectomy: Central vascular ligation and complete mesocolon excision vs D3 lymphadenectomy - How I do it?

In colon cancer surgery, ensuring the complete removal of the primary tumor and draining lymph nodes is crucial. Lymphatic drainage in the colon follows the vascular supply, typically progressing from pericolic to paraaortic lymph nodes. While NCCN guidelines recommend the removal of 10-12 lymph nodes for adequate oncological resection, achieving complete oncological resection involves more than just meeting these numerical targets. Various techniques have been developed and studied over time to attain optimal oncological outcomes. A key technique central to this goal is identifying the ileocolic vessels at their origin from the superior mesenteric vessels. Complete excision of the visceral and parietal mesocolon ensures the intact removal of the specimen, while D3 lymphadenectomy targets all draining regional lymph nodes. Although these principles emphasize different aspects, they ultimately converge to achieve the same goal of complete oncological resection. This article aims to simplify the surgical steps that align with the principle of central vascular ligation and mesocolon mobilization while ensuring adequate D3 dissection.

A decade long overview of damage control laparotomy for abdominal gunshot wounds.

Over the last three decades, damage control laparotomy (DCL) has become important in the management of abdominal gunshot wounds (GSW). This paper reviews the experience of a single institution over a decade with the use of DCL for GSW of the abdomen. Longitudinal data (2013-2022) was collected from the Hybrid Electronic Medical Registry database to identify all patients with an abdominal GSW over the study period. The data was stratified based on patients who underwent DCL and those who did not. Descriptive analysis was completed to summarise the raw data. Univariate and multivariate analysis was completed to identify variables associated with undergoing DCL. There were 135 patients (32%) who underwent DCL and 290 patients (68%) who did not. Colonic, small bowel, mesenteric, hepatic, pancreatic and intra-abdominal vessel injuries were associated with the need for DCL (P<0.05). In total, 85 of the 135 (63%) patients who underwent DCL required more than one damage control technique. There were 45 (33%) mortalities in the DCL group compared to 16 mortalities (6%) in the non-DCL group (P<0.001). One third of patients who underwent a laparotomy following a gunshot wound to the abdomen had a DCL. The indications for DCL include both physiological criteria and injury patterns. DCL is associated with significant morbidity and mortality. Efforts need to be directed towards refining the indications for DCL in this group of patients to prevent inappropriate application of this potentially lifesaving technique.

Quadruple (1440 degrees) intestinal volvulus

Key Clinical MessageA whirl sign on contrast‐enhanced abdominal CT scan is indicative of intestine twisted around the mesenteric vessels, and is observed in cases of strangulated obstruction, signaling compromised intestinal circulation. In cases of intestinal volvulus, surgery is necessary to untwist the affected bowel, and resection is necessary if necrosis is present.AbstractA 31‐year‐old Japanese man presented with acute lower abdominal pain and vomiting. Contrast‐enhanced abdominal computed tomography (CT) revealed a 1440‐degree clockwise torsion of superior mesenteric artery and a whirl sign. Intestinal volvulus in adulthood with a background of malrotation is extremely rare. Contrast‐enhanced CT is effective for diagnosis.

Laparoscopic-Assisted Colonic Derotation in Patients With Hirschsprung Disease

BackgroundChildren with Hirschsprung disease (HSCR) proximal to the splenic flexure or those needing a redo pull-through (PT) are at risk for tension and ischemia of the PT which could result in leak, stricture, or loss of ganglionated bowel. Colonic derotation is a technique used to minimize tension and avoid duodenal obstruction. The aim of this study was to describe this technique and outcomes in a series of patients requiring this intervention. MethodsAll patients underwent initial diversion and colonic mapping. The derotation procedure involves mobilization of the remaining colon, counterclockwise rotation via the stoma closure site, placement of the pull through (the right colon) lying on the right of the pelvis, and ligation of the middle colic artery with preservation of the marginal branch running from the ileocolic artery. This maneuver prevents compression of the duodenum by the mesenteric vessels and allows for an isoperistaltic, tension-free anastomosis. Intraoperative indocyanine green fluorescence angiography (ICG-FA) was utilized in many of the cases to map the blood supply of the pull-through colon. We reviewed outcomes for all children with HSCR who underwent colonic derotation from 2014 to 2023. Descriptive statistics were performed. ResultsThere were 37 children included. Most were male (67.5%) with the original transition zone proximal to the rectosigmoid (81.1%). The median age at PT was 9.3 months [6.1–39.7]. Median operative time was 6.6 h [4.9–7.4] and 19 cases (51.4%) used ICG-FA. Most children had no 30-day postoperative complications (67.6%); in those who did develop complications, readmissions for electrolyte imbalance was most common (50.0%).There were zero cases of anastomotic leak at PT anastomosis. At long-term follow up, median 4.4 years [2.3–7.0], three children (8.1%) developed an anastomotic stricture, all were amenable to anal dilation, and five experienced episodes of enterocolitis (14.7%). Most children had between 1 and 4 stools per day (58.8%). ConclusionColonic derotation is a useful strategy to ensure well-perfused colonic length, protect the marginal artery blood supply, avoid duodenal compression, and ensure a tension-free anastomosis with minimal complications. Type of StudyOriginal research, retrospective cohort. Level of EvidenceIII.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown. In this study, we utilized human dermal lymphatic endothelial cells (HDLECs) and an inducible, lymphatic endothelial cell (LEC)-specific Zmiz1 knockout mouse model to investigate the role of Zmiz1 in LECs. Transcriptional profiling of ZMIZ1-deficient HDLECs revealed downregulation of genes crucial for lymphatic vessel development. Additionally, our findings demonstrated that loss of Zmiz1 results in reduced expression of proliferation and migration genes in HDLECs and reduced proliferation and migration in vitro. We also presented evidence that Zmiz1 regulates Prox1 expression in vitro and in vivo by modulating chromatin accessibility at Prox1 regulatory regions. Furthermore, we observed that loss of Zmiz1 in mesenteric lymphatic vessels significantly reduced valve density. Collectively, our results highlight a novel role of Zmiz1 in LECs and as a transcriptional regulator of Prox1, shedding light on a previously unknown regulatory factor in lymphatic vascular biology.

Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials.

Ca2+ signalling plays a crucial role in determining lymphatic muscle cell excitability and contractility through its interaction with the Ca2+-activated Cl- channel anoctamin 1 (ANO1). In contrast, the large-conductance (BK) Ca2+-activated K+ channel (KCa) and other KCa channels have prominent vasodilatory actions by hyperpolarizing vascular smooth muscle cells. Here, we assessed the expression and contribution of the KCa family to mouse and rat lymphatic collecting vessel contractile function. The BK channel was the only KCa channel consistently expressed in fluorescence-activated cell sorting-purified mouse lymphatic muscle cell lymphatic muscle cells. We used a pharmacological inhibitor of BK channels, iberiotoxin, and small-conductance Ca2+-activated K+ channels, apamin, to inhibit KCa channels acutely in ex vivo isobaric myography experiments and intracellular membrane potential recordings. In basal conditions, BK channel inhibition had little to no effect on either mouse inguinal-axillary lymphatic vessel (MIALV) or rat mesenteric lymphatic vessel contractions or action potentials (APs). We also tested BK channel inhibition under loss of ANO1 either by genetic ablation (Myh11CreERT2-Ano1 fl/fl, Ano1ismKO) or by pharmacological inhibition with Ani9. In both Ano1ismKO MIALVs and Ani9-pretreated MIALVs, inhibition of BK channels increased contraction amplitude, increased peak AP and broadened the peak of the AP spike. In rat mesenteric lymphatic vessels, BK channel inhibition also abolished the characteristic post-spike notch, which was exaggerated with ANO1 inhibition, and significantly increased the peak potential and broadened the AP spike. We conclude that BK channels are present and functional on mouse and rat lymphatic muscle cells but are otherwise masked by the dominance of ANO1. KEY POINTS: Mouse and rat lymphatic muscle cells express functional BK channels. BK channels make little contribution to either rat or mouse lymphatic collecting vessel contractile function in basal conditions across a physiological pressure range. ANO1 limits the peak membrane potential achieved in the action potential and sets a plateau potential limiting the voltage-dependent activation of BK. BK channels are activated when ANO1 is absent or blocked and slightly impair contractile strength by reducing the peak membrane potential achieved in the action potential spike and accelerating the post-spike repolarization.

Abstract 1078: A Cross-species Platform And Phosphoproteomics Analysis To Mitigate Vegfri-induced Hypertension And Endothelial Dysfunction

Introduction: Vascular endothelial growth factor receptor inhibitors (VEGFRis) are a class of tyrosine kinase inhibitors (TKIs) used to treat human and canine cancers, but these drugs also cause hypertension (HTN) and endothelial cell (EC) dysfunction. Purpose: We combined phosphoproteomic analysis in ECs with a cross-species in-vitro and in-vivo approach to identify mitigating therapies for VEGFRi-induced EC dysfunction and HTN. Methods and Results: We developed a sorafenib-induced HTN mouse model showing increased blood pressure, mesenteric resistance vessel EC dysfunction (decreased phosphorylation of Ser1177 on endothelial nitric oxide synthase [p-eNOS], increased endothelin-1 [ET-1]), and renal glomerular endotheliosis. Human umbilical vein ECs were treated with VEGFR TKIs, non-VEGFR TKIs, and cardiovascular drugs. Phosphoproteomic mass spectrometry and a marker selection algorithm identified a 14-phosphopeptide signature differentiating VEGFR TKIs from non-VEGFR TKIs. The signature peptide RBM17 pS222 increased with VEGFRi treatment in human, canine, and mouse aortic ECs, correlating with reduced p-eNOS. By screening for cardiovascular drugs that reverse the VEGFRi phosphoproteomic signature, we found alpha-adrenergic antagonists, particularly doxazosin, had the most anti-correlated signatures. Doxazosin prevented VEGFRi-induced EC dysfunction in primary aortic ECs across species. In mice, doxazosin reversed sorafenib-induced EC dysfunction in resistance vessels without affecting blood pressure or renal glomerular endotheliosis. Conversely, lisinopril reduced HTN and glomerular endotheliosis but not EC dysfunction. Preliminary results from our clinical trial in canine cancer patients confirmed that toceranib induced HTN and showed that both doxazosin and lisinopril significantly lowered blood pressure in dogs with cancer and VEGFRi-induced HTN. Conclusion: Our study demonstrates the utility of phosphoproteomics and cross-species analysis in identifying EC-protective effects of doxazosin in VEGFRi-induced HTN. Our mouse data suggest distinct mechanisms for VEGFRi-induced EC dysfunction and HTN, potentially involving renal glomerular damage.